Effects of oral supplementation with plant superoxide dismutase extract on selected redox parameters and an inflammatory marker in a 2,000-m rowing-ergometer test, Source Dept. of Water Sports, University School of Physical Education in Poznan, Gorzów, Poland.
Oral supplementation with melon superoxide dismutase extract promotes antioxidant defences in the brain and prevents stress-induced impairment of spatial memory. Source Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan.
Influence of an orally effective SOD on hyperbaric oxygen-related cell damage, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm
Genotoxicity of hyperbaric oxygen and its prevention: what hyperbaric physicians should know. Gröger M, Radermacher P, Speit G, Muth CM. Source Researcher at Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Universitätsklinikum Ulm
Could a photobiological test be a suitable method to assess the anti-oxidant effect of a nutritional supplement Glisodin? Mac-Mary S, Sainthillier JM, Courderotmasuyer C, Creidi P, Humbert P.
GliSODin, a vegetal sod with gliadin, as preventative agent vs. atherosclerosis, as confirmed with carotid ultrasound-B imaging. Source Association Nationale de Prevention Médicale
Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Source ISOCELL
Intestinal cell targeting of a stable recombinant Cu-Zn SOD from Cucumis melo fused to a gliadin peptide.
Effects of a gliadin-combined plant superoxide dismutase extract on self-perceived fatigue in women aged 50-65 years. Houghton CA, Steels EL, Fassett RG, Coombes JS. Source School of Human Movement Studies, University of Queensland
Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping. Source Abteilung Thorax- und Gefässchirurgie, Universitätsklinikum Ulm
Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase. Source Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University
Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity.
Wheat gliadin promotes the interleukin-4-induced IgE production by normal human peripheral mononuclear cells through a redox-dependent mechanism.
Abstract of the studies available on PubMed for GliSODin, the unique SOD with proven bio-activity.

The potential benefits to health of antioxidant enzymes supplied either through dietary intake or supplementation is still a matter of controversy. The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.e. the superoxide dismutase, SOD) during the gastrointestinal digestive process, but also promoted, in vivo, the cellular defences by strengthening the antioxidant status. The effects of supplementation for 28 days with a standardized melon SOD extract either combined (Glisodin®) or not with gliadin, were evaluated on various oxidative-stress biomarkers. As already described there was no change either in superoxide dismutase, catalase or glutathione peroxidase activities in blood circulation or in the liver following non-protected SOD supplementation. However, animals supplemented with Glisodin® showed a significant elevation in circulated antioxidant enzymes activities, correlated with an increased resistance of red blood cells to oxidative stress-induced hemolysis. In the presence of Sin-1, a chemical donor of peroxynitrites, mitochondria from hepatocytes regularly underwent membrane depolarization as the primary biological event of the apoptosis cascade. Hepatocytes isolated from animals supplemented with Glisodin® presented a delayed depolarization response and an enhanced resistance to oxidative stress-induced apoptosis. It is concluded that supplementation with gliadin-combined standardized melon SOD extract (Glisodin®) promoted the cellular antioxidant status and protected against oxidative stress-induced cell death
Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress,Phytother Res. 2004 Dec;18(12):957-62. doi: 10.1002/ptr.1542.,Ioannis Vouldoukis, Marc Conti, Pascal Krauss, Caroline Kamaté, Samantha Blazquez, Maurel Tefit, Dominique Mazier, Alphonse Calenda, Bernard Dugas

Purpose: To demonstrate the efficacy of GliSODin on the following parameters:
· Modification of the Minimum Erythematous Dose (MED*)
· Incidence on the induced actinic erythema in healthy subjects:
- By demonstrating the intensity of the colour by chromometry
- By observing the micro vascularisation by videocapillaroscopy
Minimum Erythematous Dose: GliSODin induced an increase in the MED in the phototypes II, 8 times greater than that of the placebo.
Actinic Erythema:As a result, the redness induced by the actinic erythema decreased more quickly in the GliSODin group. Therefore, the increase in the number of capillaries assessed by videocapillaroscopy was higher in the GliSODin group
Conclusion: The studies already published have shown that GliSODin protects the cells by activating the internal antioxidant defence system that are necessary for the elimination of the free radicals produced by oxidative stress. This study confirms the efficacy of GliSODin in the prevention of the consequences of oxidative stress resulting from exposure to the sun. This efficacy is of particular interest for phototypes II that represent a major part of the consultations in dermatology. In the GliSODin group, the MED increased, thereby resulting in a rapid reduction in actinic erythema as from the intake of the product. It would be interesting to develop this study by working on a larger number of phototypes II. This study was presented on 27 and 28 May at the CARD (Annual Congress of Dermatological Research) meeting in Brest and will be published.
Evaluation of the Effect of GliSODin on the Intensity of Actinic Erythema Induced with Radiation, Pr Humbert's dpt, Besancon, November 2004,

In a prospective, double-blind, randomised placebo controlled study, we tested the hypothesis that a new formulation consisting of wheat gliadin chemically combined with a vegetal (thus orally effective) preparation of superoxide dismutase (SOD) allows to prevent hyperbaric oxygen (HBO)-induced oxidative cell stress.
Twenty heal)y volunteers were exposed to 100% oxygen breathing at 2.5 ATA for a total of 60 min. DNA strand breaks (tail moments) were determined using the alkaline version of the comet assay. Whole blood concentrations of reduced (GSH) and oxidised (GSSG) glutathione and F2-isoprostanes, SOD, glutathione peroxidase (GPx) and catalase (Cat) activities and red cell malondialdehyde (MDA) content were determined.
After HBO exposure the tail moment (p = 0.03) and isoprostane levels (p = 0.049) were significantly lower in the group that received the vegetal formulation. Neither SOD and Cat nor GSH and GSSG were significantly affected by this preparation or HBO exposure. By contrast, blood GPx activity, which tended to be lower in the SOD group already before the HBO exposure (p = 0.076), was significantly lower afterwards (p = 0.045).
We conclude that an orally effective SOD–wheat gliadin mixture is able to protect against DNA damage, which coincided with reduced blood isoprostane levels, and may therefore be used as an antioxidant.
Influence of an Orally Effective SOD on Hyperbaric Oxygen-related Cell Damage, GliSODin, Free Radical Research, Volume 38 Number 9 (September 2004), pp. 927–932

Prevention of cardiovascular disease should target high-risk subjects based on genetic/familial factors, blood chemistry, blood pressure, body mass index (BMI), and a history of/or current cigarette smoking. We selected active adults (n=76) aged 30-60 and investigated these risk factors, in order to recommend preventive measures. Another interesting variable is the preclinical status or atheroma of the arterial (carotid) wall or lumen. We also investigated the presence of oxidative stress in, and the anti-oxidant status of these subjects. We studied the anti-oxidative efficacy of superoxide dismutase (SOD) and variations of malondialdehyde (MDA). Supplementation with GliSODin®, a vegetal SOD associated with gliadin, was effective in controlling the thickness of the carotid artery intima and media layers as measured by ultrasonography- B. We could demonstrate the preventive efficacy of GliSODin at a preclinical stage in subjects with risk factors of cardiovascular disease.
GliSODin, a vegetal SOD with gliadin, as preventative agent vs. atherosclerosis, as confirmed with carotid ultrasound B imaging, Extract of European Annals of Allergy and Clinical Immunology - volume 39 - n° 2 - 2007

The aim of this study was to investigate the effect of plant superoxide dismutase extract (GliSODin) supplementation on the balance of oxidants and antioxidants in the serum and erythrocytes of competitive rowers. The double-blinded study included 19 members of the Polish rowing team who were participating in a preparatory camp. Subjects were randomly assigned to the supplemented group (n = 10), who received 2 capsules (500 mg) of GliSODin extract once daily for 6 weeks, or the placebo group (n = 9). At the beginning and end of the study, subjects performed a 2,000-m maximum- effort test on a rowing ergometer. Blood samples were taken from the antecubital vein before each exercise test, 1 min after completing the test, and after a 24-hr restitution period. The following redox parameters were assessed in erythrocytes: superoxide dismutase (SOD) activity, glutathione peroxidase activity, and concentrations of thiobarbituric- acid- reactive substances. In addition, creatine kinase activity and total antioxidant capacity were measured in plasma samples, lactate levels were determined in capillary blood samples, and C-reactive protein and lactate dehydrogenase concentrations were measured in serum. After supplementation, SOD activity was signicantly higher (p = .0037) in the supplemented group than the placebo group, and C-reactive protein was signicantly (p = .00001) lower in athletes receiving GliSODin than those in the placebo group. In conclusion, supplementation with an extract rich in SOD activity promoted antioxidant status and protected against increased inflammation in the serum of professional rowers but had no effect on oxidative damage induced by exhaustive exercise.
Effects of Oral Supplementation With Plant Superoxide Dismutase Extract on Selected Redox Parameters and an Inflammatory Marker in a 2,000- m Rowing- Ergometer Test GliSODin, International Journal of Sport Nutrition and Exercise Metabolism, 2011, 124-134, Anna Skarpanska-Stejnborn, Lucja Pilaczynska-Szczesniak, Piotr Basta, Ewa Deskur-Smielecka, Donata Woitas-Slubowska, and Zdzislaw Adach

Abstract : Oxidative stress, the natural consequence of the oxygen metabolism, is normally controlled by antioxidant endogenous defense systems.When these prove to be insufficient, cellular lesions develop that result in ageing but also in some pathological processes.The powerful natural antioxidant enzyme superoxide dismutase (SOD) acts at the very source of the chain reaction resulting in reactive types of oxygen and therefore constitutes the first and one of the main links of the defense process against free radicals.Unfortunately, due to the fragility of its molecular structure, non-protected SOD is inactivated in the digestive tract.Thanks to a coupling process with gliadin, a protein extracted from wheat,a SOD of vegetable origin (melon extract rich in SOD) is now available orally.Several in vivo studies on animals as well as a clinical trial using healthy volonteers confirmed the preservation of the antioxidant activity of the SOD enzyme after oral administration;an action moreover combined with anti-inflammatory and immunomodulatory properties.
Keywords: Superoxide dismutase (SOD) – Gliadin – Vegetable origin – Oral bioactivity – Antioxidant action – Antiinflammatory and immunomodulatory properties – Free radicals – Degenerative and diseases and ageing – Clinical trial – In vivo studies
La superoxyde dismutase, puissant antioxydant naturel, désormais disponible par voie orale
Résumé : Le stress oxydatif, conséquence naturelle du métabolisme de l’oxygène, est normalement contrôlé par des systèmes de défense antioxydante endogènes. Lorsque ceux-ci s’avèrent insuffisants, il en résulte des lésions cellulaires impliquées dans le vieillissement mais également dans certains processus pathologiques. Puissante enzyme antioxydante naturelle, la SOD agit à la source même de la réaction en chaîne induite par les espèces réactives de l’oxygène et constitue donc le premier et l’un des principaux maillons du processus de défense contre les radicaux libres. Malheureusement, en raison de la fragilité de sa structure moléculaire, la SOD non protégée est inactivée dans le tube digestif. Grâce à un procédé de couplage à la gliadine, protéine extraite du blé, on dispose désormais d’une SOD d’origine végétale (extrait de melon riche en SOD) bioactive par voie orale. Plusieurs études in vivo chez l’animal ainsi qu’une étude clinique chez des volontaires sains ont effectivement confirmé le maintien de l’activité antioxydante de l’enzyme SOD après absorption par voie orale, action par ailleurs combinée à des propriétés anti-inflammatoires et immunomodulatrices.
Mots clés : Superoxyde dismutase (SOD) – Gliadine – Origine végétale – Bioactivité par voie orale – Action antioxydante – Propriétés anti-inflammatoires et immunomodulatrices – Radicaux libres – Maladies dégénératives et vieillissement – Étude clinique – Études in vivo
Superoxide dismutase SOD, a powerful antioxidant now available orally - Proof of concept, F. Joanny Menvielle-Bourg, Phytothérapie (2005) Numéro 3: 1-4

Redox reactions are important in the mechanisms of resistance. Reactions of an organism on different stimulus at the molecular level is characterized by oxidation of the diverse important bio-substrates and formation of the superoxide radicals of the peroxidate compounds.
It is widely known, that the free radical is an atom, a molecule, a particle of the substances without twinned electron at the external orbit and therefore the particles - free radicals are highly "aggressive" in oxidizing the compounds that differ on chemical structure and biological activity. As a consequence, characteristics of these compounds change significantly and the oxidizing stress comes. A multicomponent system rises to protect normal metabolic processes against this aggressive free-radical oxidation. Free radical aggression increases in conditions of inconsistency of the antioxidant protection that inevitably leads to development of various pathological states and illnesses of different systems of an organism.
Metabolic disorders underlie injury of cells, tissues and organs, affected by the ischemic stress and, for example, occur in cardiovascular diseases. Currently there are no doubts in importance of the various disturbances of cardiovascular system, digestive system, skin diseases from oxidizing stress in pathogenesis after the ability of an organism to self-protection against such influence decreases. As a result, conditions for adverse clinical courses and their synchronization occur, arises predisposition to new diseases, the status combined, coupling, compromised pathologies is formed.
Use of a complex treatment of antioxidants and antihypoxic medications allows breaking this vicious circle down.
Antioxidants block activation of the free radical processes (formation of active forms of oxygen) and lipid peroxidation of the cellular membranes. Their effect is realized through restoration of free radicals into a stable molecular formula that is incapable of auto-oxidization.
Primary antioxidants, produced in the organism, include SOD, catalase and glutation peroxidase. Secondary antioxidants received with food - vitamins А, С, Е; minerals (selenium, zinc, copper, magnesium) and other substances, including polyphenols of vegetable origin. These food antioxidants assist in maintenance of the antioxidant reserve, therefore performing secondary role in the system.
Establishing the connection between the balance of prooxidants and antioxidants in the organism, development of the oxidative stress and increase of the risk of a number of chronic and age degenerative diseases has whetted interest to the natural antioxidants recently.
Using BAAs that containing antioxidants is an efficient form of primary and secondary prophylaxis of a number of nosologic formations. It is also a measure of complementary therapy of chronic diseases. The extractions containing SOD is the most valuable among the antioxidants of vegetable origin, as it assists to increase of protection against cellular destruction and revealing the ability of direct neutralization of the superoxid, one of the most harmful free radical substances.
First characteristics of the superoxiddismutase has been described by McCord and Fridovic in 1968. SOD is an enzyme that assists removal of the superoxid radical and therefore creates a system that protects from negative impact of the radical that can originate from atmosphere oxygen in normal conditions. The enzyme also has a major role in preventing harmful effect of the atmospheric O2on cellules and organisms. Like most other protective components that are created in the organism, SOD synthesis decrease with the age, while cellular oxidant susceptibility increases. All these lead to senility and diseases. Reception of the antioxidants, in particular - SOD, with food or as biologically active addition increases the existing individual reserve and can prevent intensification of those chronic sufferings, pathogeny of which is affected by the oxidizing process. It is known that such diseases include disorders of cardiovascular system (ischemic disorders, idiopathic hypertension), rheumatic diseases, chronic diseases of respiratory organs, ulcer, and skin diseases.
Natural antioxidants are represented by multicomponent systems with compound and varied interaction between its components. Such components often appear to be unstable. Half-life period of natural SOD (of human, vegetable and animal nature) in plasma is significantly different. However all the forms possess a common disadvantage - poor absorption at peroral intake and destruction by the hydrochloric acid.
BAA "Glisodin" is a capsule with melon extract, containing superoxyddismutase, gliadine, maltodextrine, extracted from wheat, mannitol 60, magnesium stearate, aerosil. In order to minimize its destruction in the stomach we have included albumen of wheat seeds (gliadin) into the "Glicodin" preparation. Gliadin prevents destruction of the SOD of melon by digestive juices and assists better absorbability in small intestine. Magnesium is viewed as a protector from cardiovascular diseases, it is a co-factor of more than 250 ferments involved in the carbohydrate and energy metabolism. Its lack results in increase of calcium scurf in vessels, heart and kidneys. All components are of natural origin and not modified genetically. Every BAA capsule weights 250 mg.
Carrying out the research of clinical efficiency of the new biologically active addition "GLISODIN" for cure of patients with chronic gastrointestinal disturbances, allergy-driven skin diseases is the purpose of the report.
1. Treatment by the BAA"Glisodin" with antioxidant effect promotes faster knocking over the symptoms and improvement of the general somatic status of the patients suffering ischemic disorder and idiopathic hypertension, ulcer, skin diseases.
2. Therapeutic effects on the patients receiving the BAA "Glisodin" with antioxidant action in addition to the basic treatment are reached earlier and they are more stable.
3. After inclusion of the BAA "Glisodin" into the basic treatment schemes, the psychological status of the patients improves, the astheny level decreases, functions of attention, memory, the counting, associations, kinetics improve, sleep quality improves.
4. Treatment with BAA "Glisodin" increases resistibility to environmental factors.
5. Applying the BAA "Glisodin" in antiulcer therapy leads to faster healing of the erosion defeats of the mucous stomach membrane, normalization and acceleration of the reparative processes.
6. Inclusion of the antioxidant BAA "Glisodin" into the structure of therapy of ulcer, results in reduction of the HP sowing of the mucous stomach membrane.
7. The BAA "Glisodin" positively influence on the lipid exchange, promotes increase of the anti atherogenic fraction of the high density lipoproteids and reduction of the level of the little and very little density lipoproteids, including for the patients with the level of the specified parameters within the limits of referencial meaningss.
8. For the patients suffering skin diseases the BAA "Glisodin" promotes regress of skin lesion reducing the sizes of the skin lesion, reduces intensity of pathological processes, renders positive immunomodulating action owing to increase in quantity of natural killers, decrease in quantity of T-surpressors, improvement of the immunoregulator index, and functional activity of lymphocytes.
Research of in-patient efficaciousness of the biologically active addition to food Glisodin® in therapeutic practice, Gouvpo St. Petersberg State Medical Akademy Im I.I. Mechnikova Of The Federal Agency Of Public Health And Social Development

Oxidative stress from reactive oxygen species has been implicated in many diseases including age related macular degeneration, in which the retinal pigment epithelium is a primarytarget. The aim of this study was to evaluate the protective effect of dietary supplementation in Superoxide Dismutase (SOD) on light–induced oxidative stress in a mouse model for aging, the senescence– accelerated mouse prone 8 (SAM P8).
plasma antioxidant capacity was increased by 30 % in animals treated by SOD. Superoxide anion levels were increased up to 50% (p<0.01) in the ganglioncell layer, and by 300 % in the outer nuclear layer (p<0.01) in all light–exposed mice as compared to non exposed animals. No differences were observed between SAM R1 and SAM P8. Within light exposed animals, the SOD supplementation significantly reduced the superoxide anion levels (p<0.05)
Dietary SOD (Super Oxide Dismutase) protects against light-induced retinal oxidative stress in young senescence accelerated mice (SAM), GliSODin, Poster 2089 / B639, May 1sr 2006, Association for Research in vision and ophthalmology - eyes

Background : Generation of oxygen-derived radicals has been demonstrated to be the major mechanism of ischemia-reperfusion induced damage [1]. Reactive oxygen species interact with DNA leading to structural alteration [2]. Recently, we showed that GliSODin®, an orally effective mixture of SOD and wheat gliadin, protected against hyperbaric oxygen (HBO)-induced DNA damage assessed by single cell gel electrophoresis (comet assay) [4]. Since DNA damage was less marked than in previous studies [3], we investigated whether GliSODin® is also protective when during more severe oxidative stres
Materials and Methods: After 2 weeks of feeding once a day with 1250 IU of GliSODin® (n = 9) or vehicle (n = 5) blood samples were taken from swine (body weight 50 (47-53) kg). DNA damage (tail moment in the alkaline version of the comet assay) was evaluated in isolated lymphocytes (Ficoll gradient) before and after HBO exposure (2 hrs at 4 bar O2) (GliSODin® n=9, Vehicle n=5). Comet assay was performed as well in whole blood samples taken at different time points (before and after 30 minutes thoracic aortic cross-clamping as well as 2 and 4 hours after declamping) during thoracic aortic surgery (GliSODin® n=8, Vehicle n =7). Plasma 8- isoprostane (8-epi Prostaglandin F2) concentrations as a direct marker of lipid peroxidation were determined using an enzyme immunoassay kit (Cayman Chemicals, Ann Arbor, MI) in portal (PV) and hepatic venous (HV) blood before and after aortic cross clamping. Antioxidant enzyme SOD (RANSOD kit, Randox Laboratories Ltd, U.K.) and catalase activity (assayed by a method in which the disappearance of peroxide is followed spectrophotometrically) were assessed on whole blood samples taken during aortic cross clamping and on lymphocytes isolated before and after HBO exposure. Data are median (range). After exclusion of normal distribution data using a Kolmogorov -Smirnov -test, time dependent differences within groups during aortic surgery were analyzed with a Friedman repeated measures ANOVA and, if appropriate, by a Dunn’s test. Differences before and after HBO exposure were analyzed with a Wilcoxon signed rank test. Intergroup differences were analyzed with Mann-Whitney rank sum test.
Results There was no difference in DNA damage before exposure to HBO (p= 0.255 GliSODin® vs. Vehicle). GliSODin® bounded (tail moment from 0.08 (0.06-0.12) to 0.11 (0.07-0.23), p=0.020) the otherwise marked increase (Vehicle: tail moment from 0.11 (0.09-0.13) to 0.43 (0.40-0.73), p=0.063) in DNA strand breaks after HBO exposure (p=0.005 GliSODin® vs. Vehicle after HBO). GliSODin® also reduced oxidative DNA damage related to surgical stress and ischemia-reperfusion after aortic clamping (tail moment from 0.09 (0.08-0.11) to 0.12 (0.11-0.14), p= 0.023) in comparison to Vehicle (tail moment from 0.12 (0.11-0.15) to 0.48 (0.35-0.60). p=0.031) resulting in a statistically significant intergroup difference 2 hrs after declamping (p= 0.021, GliSODin® vs. Vehicle). While there was no intergroup difference in the baseline values of isoprostane levels (p=0.391), these values significantly increased both in hepatic venous (p=0.003) and portal venous samples (0.006). No such effect was observed in GliSODin® group. Neither SOD nor catalase activities were significantly affected by GliSODin® ingestion (baseline values GliSODin® vs. Vehicle, p= 0.289 ) or by stress related to surgery and aortic cross clamping (GliSODin® vs. Vehicle p= 0.312).
The orally efffective mixture of SOD and Gliadin GliSODin protects against oxidative DNA damage, M. Albicini, J. Kick, B. Hauser, U. Ehrmann, X. Leverve, P. Radermacher, G. Speit, C.M. Muth, M. Albicini, J. Kick, B. Hauser, U. Ehrmann, X. Leverve, P. Radermacher, G. Speit, C.M. Muth

GliSODin® has already demonstrated activation properties on the principal internal antioxidants, in particular Superoxide Dismutase (SOD), Catalase and Glutathione Peroxidase. The purpose of this trial was to assess its efficacy in solar prevention and protection
Results :
- Increase in the MED in the GliSODin group, particularly in the light phototypes (II and III) (Figure 1)
- Faster reduction in redness with Glisodin® than with placebo (Figure 2).
- Faster increase in the capillary density than with the placebo (Figure 2).
Discussion :
GliSODin® protects the cells against the negative effects of oxidative stress [1] by remaining active during intestinal passage [2], by activating the internal system of antioxidant enzyme defenses [3] and by limiting cell death resulting from oxidative stress. [4]. All of the results in this trial indicate the action of GliSODin® in solar protection. It would be interesting to test the efficacy of GliSODin® in this type of indication as a pre-treatment and to repeat the trial on a larger number of subjects, in particular on the light phototypes (II).
Evaluation of the Effect of GliSODin® on the Intensity of Actinic Erythema Induced with Radiation - Poster
S. Mac-Mary, J.M. Sainthillier, P. Creidi, J.P. Series, F. Vix, Ph. Humbert

The potential benefits to health of antioxidant enzymes supplied either through dietary intake or supplementation is still a matter of controversy. The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.e. the superoxide dismutase, SOD) during the gastrointestinal digestive process, but also promoted, in vivo, the cellular defences by strengthening the antioxidant status.
The effects of supplementation for 28 days with a standardized melon SOD extract either combined (Glisodin®) or not with gliadin, were evaluated on various oxidative-stress biomarkers. As already described there was no change either in superoxide dismutase, catalase or glutathione peroxidase activities in blood circulation or in the liver following non-protected SOD supplementation. However, animals supplemented with Glisodin® showed a significant elevation in circulated antioxidant enzymes activities, correlated with an increased resistance of red blood cells to oxidative stress-induced hemolysis. In the presence of Sin-1, a chemical donor of peroxynitrites, mitochondria from hepatocytes regularly underwent membrane depolarization as the primary biological event of the apoptosis cascade. Hepatocytes isolated from animals supplemented with Glisodin® presented a delayed depolarization response and an enhanced resistance to oxidative stress-induced apoptosis. It is concluded that supplementation with gliadin-combined standardized melon SOD extract (Glisodin®) promoted the cellular antioxidant status and protected against oxidative stress-induced cell death
Supplementation with Gliadin-combined Plant Superoxide Dismutase Extract Promotes Antioxidant Defences and Protects Against Oxidative Stress, Phytotherapy Research 18, 957–962 (2004), Ioannis Vouldoukis, Marc Conti, Pascal Krauss, Caroline Kamaté, Samantha Blazquez, Maurel Tefit, Dominique Mazier, Alphonse Calenda and Bernard Dugas

Objective: To evaluate the efficacy of superoxide dismutase (SOD) in lung function (FEV1 reversibility) and respiratory symptoms (drug scores, symptoms scores) in asthmatic and house dust mite allergic children receiving house dust mites immunotherapy.
Methods: Forty subjects aged 6–17 years old with asthma, tested positive for house dust mite allergy on skin prick test, and received immunotherapy were enrolled in this study. All subjects completed clinical based assessments and diary-based assessments for drug and symptom scores. Following a four-week baseline assessment, all subjects were randomized to receive SOD or placebo. Respiratory symptoms (drug and symptoms score) and FEV1 were evaluated at the end of the 1st, 2nd, 3rd, and 4th weeks after randomization. Drug score, symptoms score, and FEV1 reversibility test results were analyzed using a Paired t test and repeated measure of ANOVA.
Results: There was a significant difference in drug scores, symptoms score, and FEV1 reversibility test outcomes between SOD and placebo. SOD group showed a significant decrease in all outcome measures compared to those in placebo group.
Conclusions: The use of SOD as antioxidants is effective in accelerating symptom relief for children with asthma and house dust mite allergy receiving house dust mite immunotherapy.
Keywords: Allergic asthma, antioxidant, drug score, immunotherapy, symptoms score
Use of Superoxide Dismutase in Accelerating Symptom Relief in Asthmatic and House Dust Mite Allergic Children Receiving House Dust Mite Immunotherapy, Anang Endaryanto, Zahrah Hikmah, Ariyanto Harsono

ABSTRACT: While integrity is essential to confer a pharmacological effect to active enzymes when administered to the oral route, proteins often sh,ow a poor bio-availability because they are rapidly eliminated from the alimentary canal before absorption. In order to avoid this problem we evaluated the propensity of a combination of a melon SOD extract (Cucumis melo.L.C) with wheat gliadin (Triticum vulgare) to be orally effective compared to the melon SOD extract alone. We have previously demonstrated that the combination is the only one to promote the circulating antioxidants (mainly SOD, Gpx and Catalase) and a protective effect to free radicals induced-apoptosis [l].he CD4 to CD8 ratio increased significantly (0.66e0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats by affecting: (a) the production of IFN-y and IL-4 cytokines from primed spleen cells after stimulation with Con-A and (b) the isotypes of the antibody response (IgG, IgE and IgA).
Induction of Th1-dependent immunity by an orally effective melon Super Oxides Dismutase SOD, Current Trends in Immunology, Vol 5, 2003, I. Vouldoukis, M. Conti, J.P. Kolb, A. Calenda, D. Mazier and B. Dugas

Abstract Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study.   A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported.   The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002).   Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.
Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study, 2016 07-08; 30(4): 451-456, Serap Yucel, Bilgehan Sahin, Zeynep Gural, Vakur Olgac, Gorkem Aksu, fulya Agaoglu, Esra Saglam, Isik Aslay And Emin Darendeliler

GliSODin and eye health : The availability of oxygen determined the evolution of complex multicellular organisms.
However, oxygen metabolism also generates toxic byproducts called reactive oxygen species (ROS). These can cause cellular damage through the oxidation of several essential molecules such as proteins, lipids or DNA. This is a paradox of aerobic life; while oxygen is an absolute necessity, oxidation is the necessary consequence.
The eye is an organ that is continuously exposed to ionizing radiation, pollutants, industrial smoke, which makes the eyeballs extremely susceptible to oxidative attack. The retina is a photosensible tissue that is affected by light rays and undergoes high metabolic activity. Furthermore the retina contains a high level of PUFAs than other tissues that makes it vulnerable to the action of ROS.
Dietary SOD protects against light-induced retinal oxidative stress in young senescence accelerated mice, P.Sicard, Invest Ophthalmol Vis Sci 2006;47: E-Abstract 2089.
The aim of this study was to evaluate the protective effect of GliSODin® supplementation on light-induced oxidative stress in a mouse model for aging, the senescence-accelerated mouse prone 8 (SAM P8)
The data suggest that dietary GiSODin® supplementation is efficient to limit retinal oxidative stress by increasing plasma antioxidant capacity.
It has been identified a synergic effect of oral administration of GliSODin®, lutein and zeaxanthin on global health and on the protection of oxidative stress
The important role of oxidative stress in the development of AMD has been demonstrated.
A significance increase in oxidative activity and a decrease in antioxidant defenses in ocular fluids, tissues and plasma have been associated with DED - Dry-eye disorder - patients
The presence of high glucose levels in the blood for years produces changes in retinal vessels that cause damage to the cells and progressively to the vision. These complications caused by hyperglycemia are increased by excess generations of ROS and nitrogen species (Diabetic retinopathy)
Results of studies indicated that GliSODin could reduce the diabetesinduced oxidative stress and might be a novel approach for preventing metabolic syndrome and related oxidative stress.
Dietary SOD protects against light-induced retinal oxidative stress in young senescence accelerated mice, P.Sicard, Invest Ophthalmol Vis Sci 2006;47: E-Abstract 2089.

Background: Increased oxidative stress causes inflammation and increases angiogenesis. It presumed to promote the proliferation of endometriosis tissue. Kebar grass (Biophytum petersianum) and other herbs such as green tea and Cucumis melo, which contain high antioxidants, are expected to decrease oxidative stress, inflammation, angiogenesis, and reduced endometriosis implants.
Objective: To investigate the effects of Kebar grass, green tea, and Cucumis melo to malondialdehyde serum, tumor necrosis factor alpha, and vascular endothelial growth factor expression, and the area of the endometriotic implants.
Methods: Twenty-eight mice were divided into four groups, i.e., the first group of endometriosis mice was given Kebar grass extract; the second group was assigned green tea extract, the third group was given the combination of Cucumis melo extract–gliadin, and the last containing the untreated endometriosis mice as the control. Each treatment was given for 14 days. The data of MDA serum level, the area of the endometriotic implants, TNF-α, and VEGF expression were collected and analyzed.
Results: The MDA serum levels of the groups treated with Kebar grass extract, green tea extract, and Cucumis melo extract – gliadin were significantly lower (p=0.001) than the control group. TNF-α expression of the groups provided with each treatment also lower than the control groups (p=0.002). However, only the administration of the Cucumis melo extract–gliadin resulted in lower VEGF expression compare with the control (p=0.017). Finally, the area of the endometriotic implants of the mice models administered with each treatment was smaller than the control group (p=0.003).
Conclusion: Kebar grass as well as green tea and Cucumis melo–gliadin inhibits endometriotic implants extension by decreasing MDA serum and TNF-α expression.
Keywords: Biophytum petersianum; green tea; Cucumis melo; endometriosis; antioxidant herbs;GliSODin
Antioxidant Herbs Supplementation Inhibits Endometriosis Extension in Mice - Yuli Trisetiyono, Widjiati, Syarief Thaufik Hidayat, Noor Pramono - ISSN: 2503-2178 - https://doi.org/ 10.14710/ jbtr. v5i2.4716.

Abstract : Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from both animal and clinical research trials. In this review, the therapeutic value of oral administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated. Critical examination of the effects of SOD–gliadin supplementation is carried out, with an emphasis on its impact on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD–gliadin might have advantageous health effects. These conclusions are dependent on the condition or pathology under consideration. In general, the authors, who analyzed SOD-gliadin supplementation, support the use of SOD–gliadin supplementation as a complementary treatment rather than a therapeutic treatment. To further clarify the importance of dietary SOD–gliadin administration, additional large-scale clinical trials are recommended..
Therapeutic value of oral supplementation with melon superoxide dismutase and wheat gliadin combination, Susana Romao, Nutrition 31 (2015) 430– 436

Background :Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats and mice, with the cytotoxicity of AOM mediated by oxidative stress.
Aim of study : This study investigated the protective effect of a natural antioxidant (GliSODin) against AOM-induced oxidative stress and carcinogenesis in rat colon.
Methods : Twenty male Wistar rats were randomly divided into four groups (five rats/group). The contrai group was fed a basal diet. AOM-treated group (AOM) was fed a basal diet and received intraperitoneal injections of AOM for 2 weeks at a dose of 15 mg/kg. The GliSODin treatment group (superoxide dismutase [SOD]) received oral supplémentation of GliSODin (300 mg/kg) for 3 months, and the fourth combined group received AOM and GliSODin (AOM + SOD). Ail animais were continuously fed ad libitum until the âge of 16 weeks when ail rats were sacrificed. The colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, oxidant status (lipid peroxidation-LPO), and enzyme antioxidant System (glutathione [GSH], GSH-S-transferase, catalase, and SOD).
Results : Our results showed that AOM induced ACF development and oxidative stress (GSH déplétion and lipid peroxidation) in rat colonie cells. The concomitant treatment of AOM with GliSODin significantly ameliorated the cytotoxic effects of AOM.
Conclusion: The results of this study provide in vivoevidence that GliSODin reduced the AOM-induced colon cancer in rats, through their potent antioxidant activities.
Keyword : Aberrant crypt foci, azoxymethane, colon cancer, GliSODin, oxidative stress, rat
Protective rôle of a melon superoxide dismutase combined with gliadin (GliSODin) on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis - Fedia Baba-Ahmed, Kamilia Guedri, Fouzia Trea, Kheireddine Ouali - Fedia Baba-Ahmed, Kamilia Guedri, Fouzia Trea, Kheireddine Ouali - 2020 Journal of Cancer Research and Therapeutics

Inclusion criteria:
- Sensitive, dry or reactive skin.
- Readily irritated, fair skin.
- Hypersensitivity to sunshine, even UV radiation- induced, cutaneous pathology.
Duration of treatment and dosage:
- Patients took Glisodin for at least 15 days before their holidays: 2 x 250 mg capsules per day.
- The same dosage was maintained throughout the holidays.
- Patients sunbathed as usual and continued to use their regular sun screen (Index 20 to 100).
Conclusion : A first study conducted in 2003 by Dr. Laverdet in 15 patients had shown Glisodin to be effective in patients who experience sun-induced skin reactions. This much larger-scale study - conducted in 150 patients by 40 dermatologists spread throughout France - shows that Glisodin (at a dosage of 2 capsules a day beginning 15 days before sunbathing and throughout the holidays) prepares the skin for exposure to the sun and undeniably improves the condition of both the patient's skin and general condition
GliSODin and exposure to the sun, Open study conducted in France on 150 patients by 40 dermatologists following a protocol compiled by Catherine Laverdet, M.D., Nadine Pomarede, M.D. and Catherine Oliveres-Ghouti, M.D.

Background: Asthma is a chronic inflammatory airway disease characterized by a prevailing type 2 inflammation, airway hyperresponsiveness, and mucus hypersecretion and is driven by various factors among which oxidative molecules, called reactive oxygen species (ROS), play a major role. Superoxide dismutases (SODs) are enzymes that constitute the first line of defense against ROS. Melon SOD-gliadin, which is known as GliSODin®, is commonly used as a nutritional supplement that has proven antioxidant properties.
Objectives: In this study, we evaluated the efficacy and mechanism of action GliSODin® in the treatment of allergic asthma.
Methods: House dust mite (HDM)-induced asthmatic mice were orally exposed to GliSODin®, and airway hyperresponsiveness, lung inflammation, in vitro T-cell polarization, in vivo T-cell reactivation, and blood immunoglobulin were investigated.
Results: GliSODin® reduced airway hyperresponsiveness, lung innate and adaptive immune response, and HDM-specific IgE production. Coculturing CD4+ T-cell with HDM-sensitized dendritic cells and GliSODin® reduced T-cell polarization into Th2 and Th17 cells. Moreover, adoptively transferred CD4+ T cells from asthmatic mice exhibited a reduced reactivation of Th2 and Th17 cells following stimulation with HDM plus GliSODin®.
Conclusion: GliSODin® abrogates asthma features and reduces CD4+ T-cell polarization and reactivation. Taken together, these data suggest that GliSODin® could be used for the management of asthma symptoms.
KEYWORDS asthma, immunology, mouse model, dendritic cell, antioxidant
GliSODin® prevents airway inflammation by inhibiting T-cell differentiation and activation in a mouse model of asthma, 06 June 2023, DOI 10.3389/ falgy. 2023. 1199355, Martin Klein, Eleonore Dijoux, Marie-Aude Cheminant, Laurent Intes and Grégory Bouchaud

The present studywas conducted to evaluate in vitro and in vivo the antioxidant and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity. Peritoneal macrophages were pre-activated in vitro with 300 IU of interferon-gamma (IFN-gamma) and were then challenged in culture with IgGl/anti-IgG1 immune complexes (IgG1IC) in presence of various CME extracts. The subsequent production of free radicals (superoxide anion, nitric oxide, and peroxynitrite) and of pro-(TNF-alpha) and anti-(IL-10) inflammatory cytokines was evaluated. The CME inhibited in a dose-dependent manner the production of superoxide anion with a maximal effect at 100µg/ml. This inhibitory effect ofCMEappeared to be closely linked to the SOD activity because itwas dramatically decreased after heat inactivation of the SOD activity (HI-CME). In addition, the CME inhibited the production of peroxynitrite strengthening the antioxidant properties of this CME rich in SOD activity. The production of the pro- and anti-inflammatory cytokines, namely TNF-alpha and IL-10, being conditioned by the redox status of macrophages we also evaluated the effect of CME and HI-CME on the IgG1IC-induced cytokine production. When the SOD activity was present in the CME it promoted the IgG1IC-induced production of IL-10 instead of TNF-alpha. These data demonstrated that, in addition to its antioxidant properties, the anti-inflammatory properties of the CME extract were principally related to its capacity to induce the production of IL-10 by peritoneal macrophages. The particular properties of wheat gliadin (Triticum vulgare, Poaceae) for the oral delivery of functional proteins led us to test it in a new nutraceutical formula based on its combination with the CME thus monitoring the SOD activity release during the gastro-intestinal digestive process. In these experiments C57BL/6 mice were supplemented orally everyday during 28 days with: (1) the placebo, (2) the CME extract alone, (3) the gliadin, (4) the CME/gliadin combination, or (5) the HI-CME/gliadin combination (SOD inactivated). At the end of the supplementation period all the animals were injected intra-peritoneal (i.p.) with the pro-inflammatory cytokine IFN-gamma (300 IU) and peritoneal macrophages were harvested 24 h after to test their capacities to produce free radicals, TNF-alpha and IL-10 after triggering with IgG1IC. We demonstrated that animals supplemented during 28 days with the CME/gliadin combination were protected against the pro-inflammatory properties of IFN-gamma while the other products were inefficient. These data did not only indicate that the SOD activity is important for the antioxidant and anti-inflammatory properties of the CME extract, but also demonstrated that when the SOD activity is preserved during the digestive process by its combination with wheat gliadin it is possible to elicit in vivo the pharmacological effects of this antioxidant enzyme.
Antioxidant and Anti- inflammatory properties of a Curcumis melo LC rich in SOD, GliSODin, Journal of Ethno-Pharmacology, 2004, Ioannis Vouldoukis, Dominique Lacan, Caroline Kamate, Philippe Coste, Alphonse Calenda, Dominique Mazier, Marc Conti, Bernard Dugas

Strenuous exercise abruptly increases oxygen consumption aggravating oxidative stress by generation of free radicals. In healthy individuals, the antioxidant system defends tissues against free radical attack and superoxide dismutase (SOD) is one of the major antioxidant enzymes. Recently an effective oral preparation of SOD was developed and we evaluated its influence on exercise-related change of blood antioxidants and lactate. Forty -four healthy volunteers participated in this study and a daily dose of 1500 IU oral SOD (Glisodin®) was administered to each participant for 4 weeks. Before and after the 4 week SOD treatment, they performed the same quantity of acute cycling or treadmill exercise. Shortly before and after the exercise serum total antioxidant status (TAS), erythrocytic SOD, whole blood glutathione peroxidase (GPx), serum glutathione reductase (GR), and plasma lactate (Lac) of each participant were measured. Based on the degree of initial exercise-induced lactate increase, subjects were classified into severe exercise group (n=27) and moderate exercise group (n=17). After 4 week adminitration of oral SOD, baseline TAS and GR were significantly decreased (p max 0.01) while SOD, GPx and Lac showed no significant change. In severe exercise group, s ignificant exercise-induced increases in TAS, SOD, GR and Lac were observed before SOD treatment (p max 0.01). After 4 w eek SOD administration, this group showed significantly decreased amount of exercise-induced increases i n TAS, SOD (p max 0.05) and Lac (p max 0.01). These results suggest that exhausting exercise is responsible for a significant increase in blood TAS, SOD, GR and Lac and a 4-week administration of the newly developed oral SOD induces a significant change in oxidative status and a significant decrease in exercise-induced lactate release.
Influence of an orally effective superoxide dismutase (GliSODin) on strenuous exercise-induced changes of bllod antioxidant enzymes and plasma lactate, Y. Hong, S. Hong, Y. H. Chang, S. H. Cho

Abstract We investigated the potential protective effects of two antioxidant molecules: Glisodin, a gliadin combined copper-zinc superoxide dismutase SOD (Cu,Zn SOD)-rich melon extract, SOD is a known enzyme that has been best studied as a regulator of antioxidant defence , and an antioxidant agent N-acetylcysteine (NAC). Glisodin, given orally to rats fed a chow diet, as 180 U/d during 2 weeks in a preconditioning treatment, and then for 8 weeks, combined to a high fat/high fructose diet (HF/HFr), had more positive effects than NAC (100 mg/d), not only on oxidative stress parameters, but also on features of the metabolic-syndrome. DNA oxidative damages, lipid peroxidation, and fasting glycaemia were lower in rats receiving Glisodin than in those supplemented by NAC. In addition, insulin sensitivity was improved and mesenteric fat was significantly lower in rats fed the Fr/Fe diet plus Glisodin than in animals fed NAC supplementation. These data suggest potential beneficial effects of oral Glisodin supplementation in preventing metabolic alterations related to the metabolic syndrome.
Résumé : Nous avons comparé les effets de deux molécules antioxydantes, le Glisodin, un extrait de melon riche en superoxide dismutase Cu, Zn (Cu, Zn-SOD) combiné à de la gliadine, et un agent antioxydant la NAC, N acétyl cystéine. Les deux antioxydants ont été administrés oralement 2 semaines en pré-conditionnement à des rats nourris au régime d’entretien, puis 8 semaines associées à un régime riche en fer et en fructose induisant un stress oxydant. Le Glisodin (180 U/j) a des effets bénéfiques supérieurs à ceux de la NAC (100 mg/j) non seulement sur le stress oxydant (dommages oxydatifs aux ADN, peroxydation lipidique) mais aussi sur les paramètres du syndrome métabolique (glycémie a jeun, insulinémie, graisse mésentérique). Ces résultats suggèrent une utilisation thérapeutique du Glisodin dans le syndrome métabolique.
Positive effects of an oral supplementation by Glisodin, a gliadin-combined SOD-rich melon extract, in an animal model of dietary-induced oxidative stress / Effets bénéfiques d’une supplémentation orale par le Glisodin, un extrait de melon combiné à de la gliadine, dans un modèle animal de stress oxydant induit par l’alimentation, I. Hininger-Favier, M. Osman, A.M. Roussel, L. Intes, B. Montanari - Phytothérapie DOI 10.1007/ s10298-015- 0928-4

En raison de la fragilité de sa structure moléculaire, la SOD non protégée est inactivée dans le tube digestif.Grâce à un procédé de couplage à la gliadine, protéine extraite du blé, on dispose désormais d’une SOD d’origine végétale (extrait de melon riche en SOD) bioactive par voie orale.Plusieurs études in vivo chez l’animal ainsi qu’une étude clinique chez des volontaires sains ont effectivement confirmé le maintien de l’activité antioxydante de l’enzyme SOD après absorption par voie orale, action par ailleurs combinée à des propriétés anti-inflammatoires et immunomodulatrices.
Résumé : Le stress oxydatif, conséquence naturelle du métabolisme de l’oxygène, est normalement contrôlé par des systèmes de défense antioxydante endogènes.L orsque ceux-ci s’avèrent insuffisants, il en résulte des lésions cellulaires impliquées dans le vieillissement mais également dans certains processus pathologiques.P uissante enzyme antioxydante naturelle, la SOD agit à la source même de la réaction en chaîne induite par les espèces réactives de l’oxygène et constitue donc le premier et l’un des principaux maillons du processus de défense contre les radicaux libres.M alheureusement, en raison de la fragilité de sa structure moléculaire, la SOD non protégée est inactivée dans le tube digestif.G râce à un procédé de couplage à la gliadine, protéine extraite du blé, on dispose désormais d’une SOD d’origine végétale (extrait de melon riche en SOD) bioactive par voie orale.Pl usieurs études in vivo chez l’animal ainsi qu’une étude clinique chez des volontaires sains ont effectivement confirmé le maintien de l’activité antioxydante de l’enzyme SOD après absorption par voie orale, action par ailleurs combinée à des propriétés anti-inflammatoires et immunomodulatrices.
Mots clés : Superoxyde dismutase (SOD) – Gliadine – Origine végétale – Bioactivité par voie orale – Action antioxydante – Propriétés anti-inflammatoires et immunomodulatrices – Radicaux libres – Maladies dégénératives et vieillissement – Étude clinique – Études in vivo
La superoxyde dismutase, puissant antioxydant naturel, désormais disponible par voie orale, F. Joanny Menvielle- Bourg, Phytothérapie (2005) Numéro 3

The objectives of this study were to determine the ability of a photobiological test to assess the anti-oxidant effect of a nutritional supplement. The photoprotective effect of Glisodin® was studied by Minimal Eiythematous Dose (MED) before and after treatment and its efficacy as a treatment of actinic erythema was assessed by biometrological measurements in 49 healthy subjects (10 phototype II, 19 /ill, 20/IV). Glisodin® is known to be a promoter of the production of natural antioxidants (1, 2]. In this study, the values of MED as well as a global erythema score of all the irradiated sites of each subject were assessed with the Saidman Test before and after treatment. An actinic erythema (3 x MED) was induced by a solar simulator (Dem10lum UM®, Millier, Elektronik-Optrik, Germany) on the subjects' volar foreann. Glisodin® or a placebo were then taken orally on the following day and daily over 4 weeks. In each phototype group, half of the subjects received the active and the other half the placebo. Erythema and skin redness (a* measured with a spectrocolorimeter) were scored 24 hours after irrndiation (immediately before the first oral intake) then every week for 4 weeks. An analysis of the capillary network by videocapillaroscopy (3] completed these measurements. The intake of Glisodin® induced an increase of the MED, particularly in phototype II (8.8 % versus l.2 % for placebo group) and ill (1.7% versus 1.0%) whereas in phototype IV, no changes were observed with both products. Simultaneously, the associated score of erythema decreased (-21.2% against 7.1 % for placebo). Clinical scoring of the actinic erythema (on the forearm) decreased but no differences were observed between both groups. Redness (a*) decreased rapidly in the Glisodin® group (-37% over one week with active versus - 28.6% with placebo for phototype II, - 28.6 % versus - 28.8 % for phototype ill and - 32.5% versus-27.6% for phototype IV). The number of capillaries increased with time(+ 24.6% after one week with active versus -8.4% with placebo for phototype II, + 44.4% versus+ 17.5% for phototype ill and + 6.5 % versus+ 3.0% for phototype IV). This progression could be explained by the quicker return to basal values with GliSODin®. Although there was no significant difference between the treated group and the placebo group, this study suggests that the efficacy of the treatment in solar protection and on actinic erythema seems better on the lowest phototypes. It would be interesting to complete the investigation with a more homogeneous and numerous population (phototype II and ill), with measurements taken daily during the first week at the beginning of the study and a pre-treatment (2 or 3 weeks).
Could a photobiological test be a suitable method to assess the antioxidant effect of a nutritionnal supplement GliSODin, European Journal of Dematology, EJD 2007, 17(3) 1 13, S. Mac-mary, J.M. Sainthllller, C. Courderot Masuyer, P. Creidl, P. Humbert

The purpose of this study was to investigate the effect of antioxidant ingestion on stress-induced impairment of cognitive memory. Male C57BL/6 mice were divided into four groups as follows: (1) control mice (C mice) fed in a normal cage without immobilization; (2) restraint-stressed (RS mice) fed in a small cage; (3) vitamin E mice (VE mice), mice were fed in a small cage with a diet supplemented with vitamin E; (4) GliSODin mice (GS mice) fed in a small cage with a diet supplemented with GliSODin. RS, VE and GS mice were exposed to 12 h of immobilization daily. Five weeks later, spatial learning was measured using the MorrisWater Maze (MWM) test. Afterwater maze testing,we performed immunohistochemical analysis using 4-hydroxy-2-noneral (4-HNE) and an anti-Ki67 antibody. 4-HNE is a marker of lipid peroxidation. RS mice showed impaired spatial learning performance and an increased number of 4-HNE-positive cells in the granule cell layer (GCL) of the hippocampal dentate gyrus when compared to C mice. Moreover, RS mice showed a decreased number of Ki67-positive cells in the subgranular zone (SGZ). GS mice showed better spatial learning memory than RS mice. The number of 4-HNE-positive cells in the GCL of GS mice was significantly less than that of RS mice. The number of Ki67-positive cells in the SGZ of GS mice was significantly greater than that of RS mice. These finding suggests that GliSODin prevents stress-induced impairment of cognitive function and maintains neurogenesis in the hippocampus through antioxidant activity.
Oral supplementation with melon super oxide dismutase promotes antioxidant defences in the brain and prevents stress-induced impairments of spatial memory, GliSODin, Behavioural Brain Research 200, 2009, 15-21, Sanae Nakajima, Ikuroh Ohsawa, Kazufumi Nagata, Shigeo Ohta, Makoto Ohnob, Tetsuo ljichic, Toshia Mikamid.

Background: Recently, assisted reproductive technology has been widely accepted as a well-established procedure to treat infertility. Unfortunately, the success rate is still below expectations, whereas the rate of infertility has risen steadily. Intrauterine insemination procedure is the highest performed compared to other procedures, but the success rate is still lowest, around 10%. One cause of failure has been thought to occur due to lack of oocytes and embryos protection from cleaning of oxygen radicals. Reactive oxygen species negatively affect the maturation and interaction of gamete, fertilization, as well as acceleration of pathological states of the reproductive tract. On female reproduction, an antioxidant is essential for the maturation and quality of oocyte, implantation, placentation, fetal growth, and development of the organ. Concentrations of antioxidants have an important role in the reproduction, and interventions to reduce the influence of reactive oxygen species can improve the quality of embryos and their implantation.
Objective: To determine the effect of antioxidants (superoxide dismutase [SOD]) in ovarian stimulation response and pregnancy rates in women undergoing intrauterine insemination.
Material: Women undergoing intrauterine insemination procedures and who met the criteria of research were randomly and in double-blind divided into two groups, that is, SOD group and placebo group. During ovarian stimulation, 20 patients randomly selected were administered capsules containing 250 mg SOD (glisodin®, Kalbe Pharmaceutical, tbk.) twice a day, and the remaining 20 patients were given the same dose and color capsules containing placebo. Furthermore, ovarian activity and endometrial thickness were monitored by regular transvaginal ultrasound scans. A dose of 5000 U of hCG (Profasi, Serono Pharmaceuticals Ltd., UK) was administered when the leading cohort of follicles reached a diameter of 18–22 mm. Intrauterine insemination with prepared sperms was then performed 34–36 hours following hCG using Friedman catheter. Biochemical pregnancy is determined at day 15 after insemination with the cut-off point 25I U/mL. The data are compared between two groups and analyzed using SPSS 16 with a 95% confidence interval.
Result: Forty women underwent intrauterine insemination cycles, with 20 cycles administered to each group, SOD and placebo. There were five (12.5%) positives for chemical pregnancies, four (80%) in SOD, and one (20%) in placebo. The pregnancy rates tend to be higher in the SOD group than in the placebo group, even though it was not significantly different (p = 0.151). The ovarian stimulation determined by the number of growing follicles and endometrial thickness showed that more follicles (≥ 6 follicles) were found in SOD group (n = 10, 58.8%) than in placebo (n = 7, 41.2%); however, it was not statistically significant (p = 0.075). Endometrial thickness of 10 mm or more is statistically significant (p = 0.017), which is higher (79.2%) in SOD compared with placebo (20.8%) and yields significantly (p = 0.0251) greater pregnancy rates (n = 4, 80%) than placebo (n = 1, 20%).
Conclusions: SOD provides better stimulation response and increased pregnancy rates in intrauterine insemination program.
Keywords: antioxidant, ovarian stimulation, pregnancy rate
The role of superoxide dismutase on pregnancy rates of women undergoing intrauterine insemination - Surasandi D., Anantasika - Bali Medical Journal (Bali Med J) 2016, Volume 6, Number 1: 103-109

Abstract : We aimed to test whether attenuation of cardiac cell death can prevent diabetic cardiomyopathy. Our study showed that cardiac apoptosis as a major cellular response to diabetes is induced by hyperglycemia-derived oxidative stress. Glisodin® as a potent antioxidant prevents the development of diabetic cardiomyopathy. Eight weeks after STZ treatment, cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP labeling (TUNEL) assay. Oxidative stress in the heart tissue was evaluated by measuring GSH content, LPO level, and catalase and SOD activities. Cardiomyopathy was evaluated by measuring LDH and CPK activities.
Our results show a significant reduction in diabetesinduced increases in TUNEL-positive cells was observed in a Glisodin® treatment group. A significant decrease of reduced glutathione content, superoxide dismutase, and catalase activities in the heart of diabetic rats accompanied by increased LPO plasma levels, but not in Glisodin®-treated rats, was observed. LDH and CPK activities as biomarkers of cardiomyopathy were decreased in Glisodin®-treated diabetic rats compared to diabetic-controlled rats. In conclusion, our results suggest that attenuation of cardiac cell death by Glisodin® treatment results in a significant prevention of the development of diabetic cardiomyopathy. This process is mediated by the antioxidant effect of Glisodin® to suppress oxidative stress in the heart.
Résumé : Nous avons cherché à vérifier si l’atténuation du stress oxydatif lié au diabète pourrait diminuer le processus de la mort des cellules cardiaques. Notre étude a montré que l’apoptose cardiaque est semblable à une des réponses cellulaires majeures au diabète : induite par un stress oxydatif. La Glisodin ®, une association de SOD de melon et de protéine de blé, également un puissant antioxydant, a freiné le développement de la cardiomyopathie diabétique. Nos résultats montrent une réduction significative des TUNEL-positifs dans les cardiomyocytes, observée chez le groupe diabétique traité par la Glisodin ®. On a observé une diminution significative de la teneur en glutathion réduit, de l’activité de la SOD et de la catalase dans le coeur de rats diabétiques accompagnée par une augmentation des concentrations plasmatiques des LPO en comparaison aux rats traités par Glisodin®. Le traitement des rats diabétiques par la Glisodin® a rétabli l’augmentation de l’activité de la LDH et de la CPK exprimée chez les rats non traités. En conclusion, nos résultats suggèrent que l’atténuation de l’apoptose des cellules cardiaques par la Glisodin® assoie son effet préventif contre le développement de la cardiomyopathie diabétique. Toutefois, cet effet est principalement médié par une action antioxydante suppressive du stress oxydatif plutôt que par une action hypoglycémiante.
Glisodin®, a melon extract, attenuates cardiac muscle cell apoptosis via suppression of oxidative stress in an experimental model of streptozotocin-induced diabetes - F. Trea, K. Ouali, F. Baba-Ahmed, Y. Kadi, hytothéparie; December 2013, Volume 11, Issue 6, pp 339-347

The prevalence of the metabolic syndrome vary from 25% to 45% in human older than 40 (OMS Source) and present a strong incidence for type II diabetes and cardiovascular diseases.
Glisodin is a combination of a natural SOD and of a gliadin extract able to promote antioxidant and antiinflammatory defences of the host to fight against cellular damages caused by an excess of ROS (Vouldoukis I., 2004 : J Ethnopharmacol, vol 94 (1) :67-75 and Muth CM., 2004: Free Radic Res, vol 38 (9) : 927-32.) or again to prevent tumour progression promoted by inflammation and to reduced metastatic ability of tumour cells (Okada F., 2006: Br J Cancer, vol 94 (6) : 854-62) or finally to reduce the rate of nephropathy induced during type II diabetes (Naito Y, 2005, Biofactors, vol 23(2):85-95). These properties of Glisodin are fully consistent with that required to fight metabolic syndrome.
Relationship between Metabolic Syndrome and GliSODin, Dr Calenda, Angers, 2006

Liver hypertrophy was clearly suppressed in the Melon GliSODin® group rather than in the HC group. Furthermore, the weights of epididymal and mesenteric adipose tissues were reduced in comparison with the HC group.
Total cholesterol and TGs in the GLISODIN group decreased significantly in comparaison to the HC group. These results suggest that Melon GliSODin® may reduce lipid accumulation, which causes NASH.
To confirm whether the suppression of liver fibrosis by GliSODin® is regulated at the level of gene expression, the expression of collagen type 1 alpha (col1a1), collagen type 3 alpha 1 (col3a1) (fibrosis markers) and transforming growth factor beta (TGF-β) (an upstream regulator of col1a1 and col3a1) were determined . All three factors were suppressed in the MEL group in comparison with the HC group .
We, therefore, conclude that these changes at the level of gene expression may help prevent the onset of NASH.
In addition, we focused on lipid accumulation pathways that cause inflammation and evaluated genes involved in lipid synthesis. We measured the expression of the transcriptional regulatory factor sterol regulatory element-binding protein 1c (SREBP1c), which regulates fatty acid synthesis genes including stearoyl-CoA desaturase 1 (SCD1), acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS). In comparison with the HC group and MEL group, these genes tend to be downregulated upon GliSODin® administration. It is, therefore, considered that reduction of fatty acid synthesis in the liver could attenuate inflammation and oxidative stress.   A high-calorie diet causes fat accumulation and oxidative stress in the liver, leading to fatty liver and eventually non-alcoholic steatohepatitis (NASH). Melon GliSODin® is used as a nutritional supplement because of its antioxidant activity. This study aimed to assess the antioxidant activity of Melon GliSODin® and its effectiveness in preventing NASH, which primarily results from oxidative stress. Furthermore, we verified the protective effect of Melon GliSODin® by administering it to a mouse model of diet-induced NASH. Melon GliSODin® suppressed liver fibrosis and fat accumulation, which is characteristic of the NASH phenotype. Gene expression analysis confirmed the suppression of fat synthesis and activation of antioxidative mechanisms. These results show that Melon GliSODin® mitigates NASH onset at the molecular level, suggesting its potential application as a NASH preventive agent.   non-alcoholic steatohepatitis; non-alcoholic fatty liver disease; oxidative stress; liver disease; natural products
Keywords: non-alcoholic steatohepatitis; non-alcoholic fatty liver disease; oxidative stress; liver disease; natural products
Melon GliSODin® Prevents Diet-Induced NASH Onset by Reducing Fat Synthesis and Improving Liver Function - Anna Nakamura, Naho Kitamura, Yoko Yokoyama, Sena Uchida, Kayo Kumadaki, Kazuo Tsubota and Mitsuhiro Watanabe - Nutrients 2019, 11, 1779

Abstract : The purpose of this study was to investigate the effect of antioxidant ingestion on stress-induced impairment of cognitive memory. Male C57BL/6 mice were divided into four groups as follows: (1) control mice (C mice) fed in a normal cage without immobilization; (2) restraint-stressed (RS mice) fed in a small cage; (3) vitamin E mice (VE mice), mice were fed in a small cage with a diet supplemented with vitamin E; (4) GliSODin mice (GS mice) fed in a small cage with a diet supplemented with GliSODin. RS, VE and GS mice were exposed to 12 h of immobilization daily. Five weeks later, spatial learning was measured using the Morris Water Maze (MWM) test. After water maze testing, we performed immunohistochemical analysis using 4-hydroxy-2-noneral (4-HNE) and an anti-Ki67 antibody. 4-HNE is a marker of lipid peroxidation. RS mice showed impaired spatial learning performance and an increased number of 4-HNE-positive cells in the granule cell layer (GCL) of the hippocampal dentate gyrus when compared to C mice. Moreover, RS mice showed a decreased number of Ki67-positive cells in the subgranular zone (SGZ). GS mice showed better spatial learning memory than RS mice. The number of 4-HNE-positive cells in the GCL of GS mice was significantly less than that of RS mice. The number of Ki67-positive cells in the SGZ of GS mice was significantly greater than that of RS mice. These finding suggests that GliSODin prevents stress-induced impairment of cognitive function and maintains neurogenesis in the hippocampus through antioxidant activity.
Oral supplementation with melon superoxide dismutase extract promotes antioxidant defences in the brain and prevents stress-induced impairment of spatial memory. Sanae Nakajima, Ikuroh Ohsawa, Kazufumi Nagata, Shigeo Ohta, Makoto Ohno, Tetsuo Ijichi, Toshio Mikami, Behav Brain Res (2009), doi:10.1016/j.bbr.2008.12.038

Abstract : Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their nondiabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db/db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy.
Keywords: Oxykine, diabetic nephropathy, 8-Hydroxydeoxyguanosine, oxidative stress
Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice, BioFactors 23 (2005) 85–95, Yuji Naito, Satomi Akagiri, Kazuhiko Uchiyama, Satoshi Kokura, Norimasa Yoshida,Goji Hasegawa, Naoto Nakamura, Hiroshi Ichikawa, Shinya Toyokuni , Tetsuo Ijichi and Toshikazu Yoshikawa

Abstract
Objective: We previously reported in healthy volunteers that a cantaloupe melon extract chemically combined with wheat gliadin (melon extract/gliadin) and containing SOD, catalase and residual glutathione peroxidase (GPx), protected against DNA strand-break damage induced by hyperbaric oxygen (HBO), a wellestablished model of DNA damage resulting from oxidative stress. Aortic cross-clamping is a typical example of ischemia/reperfusion injury-related oxidative stress, and therefore we investigated whether this melon extract/gliadin would also reduce DNA damage after aortic crossclamping and reperfusion. Design: Prospective, randomized, controlled experimental study. Setting: Animal laboratory. Patients and participants: 18 anesthetized, mechanically ventilated and instrumented pigs. Interventions: After 14 days of oral administration of 1250 mg of the melon extract/gliadin (n=9) or vehicle (n = 9), animals underwent 30 min of thoracic aortic cross-clamping and 4 h of reperfusion. Measurements and results: Before clamping, immediately before declamping, and at 2 and 4 h of reperfusion, we measured blood isoprostane (immunoassay) and malondialdehyde concentrations (fluorimetric thiobarbituric acid test), SOD, catalase and GPx activities (spectrophotometric kits), NO formation (nitrate+nitrite; chemoluminescence), DNA damage in whole blood samples and isolated lymphocytes exposed to hyperbaric oxygen (comet assay). Organ function was also evaluated. Kidney and spinal cord specimen were analysed for apoptosis (TUNEL assay). The melon extract/gliadin blunted the DNA damage, reduced spinal cord apoptosis and attenuated NO release, however, without any effect on lipid peroxidation and organ function.
Conclusions: Pre-treatment with the oral melon extract/gliadin may be a therapeutic option to reduce oxidative cell injury affiliated with aortic cross-clamping.
Keywords Ischemia/reperfusion injury · Hyperbaric oxygen · Comet assay · Apoptosis · Nitric oxide · Kidney · Spinal cord
Effect of a cantaloupe melon extract / wheat gliadin biopolymer during aortic cross clamping, Intensive Care Med, Jochen Kick Balázs Hauser Hendrik Bracht Maura Albicini Sükrü Öter Florian Simon Ulrich Ehrmann Catherine Garrel Jörn Sträter Uwe B. Brückner Xavier M. Leverve Hubert Schelzig Günter Speit Peter Radermacher Claus-Martin Muth

Weakly tumorigenic and nonmetastatic QR-32 cells derived from a fibrosarcoma in C57BL6 mouse are converted to malignant cells once they have grown after being coimplanted with a gelatine sponge which induces inflammation. We administered a newly developed peroral superoxide dismutase (SOD), oxykine, and as control vehicle, gliadin and saline, starting 2 days before the coimplantation and continued daily throughout the experiment. In the oxykine group, tumour incidence was lower (41%) than in the gliadin or saline group (83 and 79%, respectively). The inhibitory effect of oxykine was lost when an individual component of oxykine was administered, that is, SOD alone and gliadin alone. The effect was also abolished when administered by intraperitoneal route. When perfused in situ with nitroblue tetrazolium, an indicator of superoxide formation, the tumour masses from gliadin and saline groups displayed intense formazan deposition, whereas, those from oxykine group had less deposition. Enzymatic activity of SOD was also increased in oxykine group. Arising tumour cells in gliadin and saline groups acquired metastatic phenotype, but those in oxykine group showed reduced metastatic ability. These results suggested that the orally active SOD derivative prevented tumour progression promoted by inflammation, which is thought to be through scavenging inflammatory cell-derived superoxide anion
Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by GliSODin, British Journal of Cancer, 2006, 854-62, F Okada, H Shionoya, M Kobayashi, T Kobayashi, H Tazawa, K Onuma, Y Iuchi, N Matsubara, T Ijich5, B Dugas and M Hosokawa

Résumé : Nous avons cherché à vérifier si l’atténuation du stress oxydatif lié au diabète pourrait diminuer le processus de la mort des cellules cardiaques. Notre étude a montré que l’apoptose cardiaque est semblable à une des réponses cellulaires majeures au diabète : induite par un stress oxydatif. La Glisodin ®, une association de SOD de melon et de protéine de blé, également un puissant antioxydant, a freiné le développement de la cardiomyopathie diabétique. Nos résultats montrent une réduction significative des TUNEL-positifs dans les cardiomyocytes, observée chez le groupe diabétique traité par la Glisodin ®. On a observé une diminution significative de la teneur en glutathion réduit, de l’activité de la SOD et de la catalase dans le coeur de rats diabétiques accompagnée par une augmentation des concentrations plasmatiques des LPO en comparaison aux rats traités par Glisodin®. Le traitement des rats diabétiques par la Glisodin® a rétabli l’augmentation de l’activité de la LDH et de la CPK exprimée chez les rats non traités. En conclusion, nos résultats suggèrent que l’atténuation de l’apoptose des cellules cardiaques par la Glisodin® assoie son effet préventif contre le développement de la cardiomyopathie diabétique. Toutefois, cet effet est principalement médié par une action antioxydante suppressive du stress oxydatif plutôt que par une action hypoglycémiante.
Abstract : We aimed to test whether attenuation of cardiac cell death can prevent diabetic cardiomyopathy. Our study showed that cardiac apoptosis as a major cellular response to diabetes is induced by hyperglycemia-derived oxidative stress. Glisodin® as a potent antioxidant prevents the development of diabetic cardiomyopathy. Eight weeks after STZ treatment, cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP labeling (TUNEL) assay. Oxidative stress in the heart tissue was evaluated by measuring GSH content, LPO level, and catalase and SOD activities. Cardiomyopathy was evaluated by measuring LDH and CPK activities. Our results show a significant reduction in diabetesinduced increases in TUNEL-positive cells was observed in a Glisodin® treatment group. A significant decrease of reduced glutathione content, superoxide dismutase, and catalase activities in the heart of diabetic rats accompanied by increased LPO plasma levels, but not in Glisodin®-treated rats, was observed. LDH and CPK activities as biomarkers of cardiomyopathy were decreased in Glisodin®-treated diabetic rats compared to diabetic-controlled rats. In conclusion, our results suggest that attenuation of cardiac cell death by Glisodin® treatment results in a significant prevention of the development of diabetic cardiomyopathy. This process is mediated by the antioxidant effect of Glisodin® to suppress oxidative stress in the heart.
Glisodin®, a melon extract that attenuates cardiac cell death via suppression of oxidative stress in the heart of Wistar rat with streptozotocin-induced diabetes, by F. Trea, K. Ouali, F. Baba-Ahmed, Y. Kadi, Phytothérapie (2013) 11: 339- 347

Background: Superoxide dismutase (SOD) reduces the reactive oxygen species formation associated with oxidative stress. An imbalance between free radicals and antioxidants can lead to accelerated aging. GliSODin® Skin Nutrients Advanced Anti-Aging Formula (GAAF) is an SOD-containing dietary nutricosmetic formulated with other nutraceuticals that promote improvements in the structure and function of the skin, including hydration, elasticity, structural integrity, and photoaging caused by oxidative stress. Tazarotene cream 0.1% (TAZ) is a United States Food and Drug Administration-approved drug indicated for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines when taken in conjunction with a comprehensive skin care and sun avoidance program.
Objective: To determine if the antioxidant, anti-aging, hydrating and skin-rejuvenating prop­erties of GAAF complement the retinoic actions of TAZ to improve the structure and function of facial skin.
Method: A 90-day comparative study of ten subjects with facial photodamage; daily topical application of TAZ was used in combination with three capsules of GAAF (780 mg each) or placebo orally, with food, per the randomization allocation.
Results: After 90 days of treatment, TAZ alone and in combination with GAAF improved fine wrinkles (↓1.2 versus 2.0), mottled hyperpigmentation (2.2 versus 2.8) and overall photodamage (1.0 versus 1.8), as well as patient-reported response to treatment (2.0 versus 1.6). At week 12, TAZ/GAAF combination treatment (Group A) versus TAZ treatment alone (Group C) was of significant clin­ical benefit, with respect to fine wrinkling (14.7%/41.7%), overall photodamage (15.6%/53.0%), skin moisture (19.1%/103.2%), skin elasticity (12.8%/87.7%), and response to treatment (8.8%/21.4%).
Conclusion: The study suggests GAAF in combination with TAZ is safe and provides signifi­cant clinical benefit with relative improvement in facial fine wrinkling, overall photodamage, skin moisture and elasticity.
Keywords: antioxidant, superoxide dismutase, anti-aging, retinoic, combined therapy, facial photodamage, nutraceuticals

Patients with acquired immunodeficiency syndrome (AIDS) present a variety of pathologic alterations that are related to oxidative stress. Previous studies have reported a reduction in the circulating antioxidant status in these patients associated with a higher production of free radicals. In the present double blind clinical investigation, the effect of the oral supplementation by a plant Superoxide dismutase extract embedded (GliSODin®) or not with Gliadin was evaluated in 35 patients with AIDS ( max 250/mm3 CD4+ T lymphocytes) that did not received any anti-retroviral therapy. The control group consisted of 30 non HIV-1-infected patients. Compared to the control group, circulating erythrocytes Cu/Zn-Superoxide dismutase (SOD1) activity and total antioxidant status were significantly (p max 0.01) decreased in AIDS patients and correlated with the increased plasmatic concentration of b2-microglobulin that reflects the activation state of macrophages. Patients receiving the GliSODin® supplementation during 21 days normalized their circulating SOD1 activity and total antioxidant status and reduced their circulating levels in b2-microglobulin, indicating a correlation between the reduction of oxidative stress and the reduction of macrophage activation. Even whether this antioxidant restoration is not associated to an improvement of the immune status or a reduction of viral load, this study demonstrates that the GliSODin® supplementation could regulate the activation state of macrophages and down-regulate the oxidative stress caused by the infectious process. In addition, by improving the antioxidant defences in AIDS patients, we prepare them to a better compliance and possibly to efficacy of the anti-retroviral therapy.
Restored antioxidant circulating capacities in AIDS west African patients receiving an antioxidant nutraceutical Cucumis melo extract rich in Superoxide dismutase activity, H Chenal, M. Conti

The powerful natural antioxydant enzyme superoxide dismutase (SOD) acts at the very source of the chain reaction resulting in reactive types of oxygen and therefore constitutes the first and one of the main links of the defence process against free radicals.Unfortunately, due to the fragility of its molecular structure, non-protected SOD is inactivated in the digestive tract.Thanks to a coupling process with gliadin, a protein extracted from wheat, a SOD of vegetable origin (melon extract rich in SOD) is now available orally.S everal in vivo studies on animals as well as a clinical trial using healthy volonteers confirmed the preservation of the antioxydant activity of the SOD enzyme after oral administration; an action moreover combined with anti-inflammatory and immunomodulatory properties.
Abstract: Oxidative stress, the natural consequence of the oxygen metabolism, is normally controlled by antioxidant endogenous defense systems.When these prove to be insufficient, cellular lesions develop that result in ageing but also in some pathological processes. The powerful natural antioxidant enzyme superoxide dismutase (SOD) acts at the very source of the chain reaction resulting in reactive types of oxygen and therefore constitutes the first and one of the main links of the defense process against free radicals. Unfortunately, due to the fragility of its molecular structure, non-protected SOD is inactivated in the digestive tract. Thanks to a coupling process with gliadin, a protein extracted from wheat, a SOD of vegetable origin (melon extract rich in SOD) is now available orally. Several in vivo studies on animals as well as a clinical trial using healthy volonteers confirmed the preservation of the antioxidant activity of the SOD enzyme after oral administration; an action moreover combined with anti-inflammatory and immunomodulatory properties.
Keywords: Superoxide dismutase (SOD) – Gliadin – Vegetable origin – Oral bioactivity – Antioxidant action – Antiinflammatory and immunomodulatory properties – Free radicals – Degenerative and diseases and ageing – Clinical trial – In vivo studies
Superoxide Dismutase (SOD), a Powerful Antioxidant, is now available Orally, F. Joanny Menvielle- Bourg, Phytothérapie (2005) Numéro 3

Free radicals, oxidative stress and antioxidants have become familiar terms through frequent warnings and information, whether for cosmetics, diet, or medication. These terms express important underlying health concerns: aging, functional decline, illness, fatigue, etc., which we are all anxious to combat. But this aspect accounts for only a part of the rich biochemistry of free radicals. These species act at the balance point between the survival and the destruction of living organisms. Their role is accordingly both complex and subtle.
A free radical is an atom or molecule that contains one or more unpaired (lone) electrons, and is, therefore, highly reactive. Oxygen in its natural state possesses two lone electrons. These can pair up with electrons on neighboring atoms by stripping electrons from them, and so initiate an oxidation chain. Other physical or chemical agents can un-pair electrons to form free radicals and trigger similar chain reactions in biological molecules. These agents include light (especially certain types of ultraviolet light), ionizing radiation (e.g., X-rays), and certain chemicals.
However, thanks to the development of a highly original dosage form, GliSODin®, made up of plant SOD extracted from melon, and gliadin, a protein from wheat, oral administration is now possible for the first time. ** The efficacy of this formulation was tested on different animal models, and recently in humans* subjected to graded oxidative stress: exposure to an atmosphere containing hyperbaric oxygen for several hours. Although such exposure causes an adaptation to oxidative stress, as stated above, this adaptation is not instantaneous, and the first exposure causes a number of anomalies. Among these effects, the DNA of white blood cells is damaged by oxidation (but fortunately only temporarily), when they are suddenly exposed to elevated oxygen levels. This damage to the DNA of white blood cells on first exposure to hyperbaric oxygen did not occur when subjects had taken GliSODin® beforehand for 15 days, showing that they were in a sense ‘pre-acclimatized’ to the oxidative stress they were to undergo.
Oxidative stress mortal danger tamed - INSERM E-0221, Pr. Xavier Leverve

Redox balance to maintain a physiological state. Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS are oxidising compounds including free radicals such as: hydroxyl radicals, superoxide anion, hydrogen peroxide and nitric oxide. They are very transient species due to their high chemical reactivity that leads to lipid peroxidation and oxidation of DNA and proteins (etc...)
Glisodin is a combination of a natural SOD and of a gliadin extract able to promote antioxidant and antiinflammatory defences of the host to fight against cellular damages caused by an excess of ROS or again to prevent tumour progression promoted by inflammation and to reduced metastatic ability of tumour cells or finally to reduce the rate of nephropathy induced during type II diabetes
Relationship between Metabolic Syndrome and Glisodin - White paper

The mRNA encoding full length chloroplastic Cu–Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD. Taking account of codon bias, both recombinant proteins were successfully expressed and produced in Escherichia coli. Both recombinant SODs display an enzymatic activity of ca. 5000 U mg−1 and were shown to be stable for at least 4 h at 37 ◦C in biological fluids mimicking the conditions of intestinal transit. These recombinant proteins were capable in vitro, albeit at different levels, of reducing ROS-induced-apoptosis of human epithelial cells. They also stimulated production and release in a time-dependent manner of an autologous SOD activity from cells located into jejunum biopsies. Nevertheless, the fused gliadin peptide enable the recombinant Cu–Zn SOD to maintain a sufficiently sustained interaction with the intestinal cells membrane in vivo rather than being eliminated with the flow. According to these observations, the new hybrid Cu–Zn SOD should show promise in applications for managing inflammatory bowel diseases.
Intestinal cell targeting of a stable recombinant Cu–Zn SOD from Cucumis melo fused to a gliadin peptide - Laurent Intes, Muriel Bahut, Pascal Nicole, Alain Couvineau, Catherine Guette, Alphonse Calenda, Journal of Biotechnology 159 (2012) 99– 107

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (!16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4 to CD8 ratio increased significantly (0.66e0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.
Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats, GliSODin, Journal of Feline Medicine and Surgery (2008) 10, Craig B Webb, Tracy L Lehman, Kelly W McCord

Résumé : Cette étude a été réalisée pour évaluer l'efficacité de la supplémentation d' un antioxydant la glisodine (SOD végétal) sur le nombre des lésions précancéreuses des foyers de cryptes aberrantes (ACF) et sur le statut oxydatif ( la peroxydation de lipide, le système de défense antioxydant) chez un model animal présentant un cancer colique induit chimiquement par l'azoxymethane ( AOM). En effet, l'administration de l'azoxymethane a provoqué un cancer du colon qui est révélé d'une part, par le formation des foyers de cryptes aberrantes (ACF) qui sont des lésions pré-néoplasiques et d'autre part par l'augmentation de la peroxydation de lipide (LPO) et une diminution considérable des taux de glutathion réduit (GSH), glutathion - S - transférase (GST), super oxyde dismutase (SOD) et la catalase (CAT) qui sont des biomarqueurs de stress oxydatif. Le traitement des rats AOM par la glisodine a diminué significativement l'incidence de tumeurs, le nombre des foyers de cryptes aberrantes (ACF), la multiplicité des cryptes avec une amélioration de l'activité de LPO et du statut de défense antioxydant GSH, GST, SOD et CAT. Ceci suggère que le glisodine peut agir en tant qu'agent chemo-préventif efficace contre le cancer du colon via la diminution des attaques radicalaires au niveau colique.
Mots clés : Glisodine, Azoxymethane (AOM), ACF, Rat, Stress oxydant, Cancer du
colon, LPO.

Abstract : This study was carried out to evaluate the effective role of the supplementation of an antioxidant the glisodine on the number of aberrant crypt foci (ACF) and oxidant status ( lipid peroxidation (LPO), enzymic antioxidants system) in azoxymethane-induced colon cancer in animal model.
Indeed, the administration of the azoxymethane caused colon carcinogenesis who is revealed on the one hand, by the formation of aberrant crypt foci (ACF) that are lesions preneoplastic and on the other hand by enhanced levels of lipid peroxidative products (LPO) and a reduction of the glutathione (GSH), glutathione - S- transférase (GST), superoxide dismutase (SOD) and the catalase (CAT) which are the biomarker of oxidative stress. Glisodine treatment to AOM-induced rat significantly decreased incidence of the tumor, number of aberrant crypts foci (ACF), the multiplicity of the crypts and the lipid peroxidation with amelioration of the activities of the antioxidant enzymes system GSH, GST, SOD and CAT. This suggests that the glisodine can act as an effective chemo-preventive agent against the colon cancer stress.
Key words: Glisodine, Azoxymethane, ACF, Rat, Oxydative stress, Colon cancer, LPO.
Etude de l'effet de la glisodine sur les réponses de détoxifications enzymatiques au cours d'un stress oxydatif cancérigène induit par l'azoxymethane chez le rat wistar - UNIVERSITE BADJI MOKHTAR-ANNABA / Faculté des sciences / Département de biologie - Mémoire présenté par Guedri kamilia

Abstract : Football players walk a fine line between optimal training and overtraining. Manipulating nutrient intake has the potential to maximize the biochemical environment necessary to induce peak performance and proper recovery. The purpose of this study was to examine the impact of supplementing the diet of Division I football players with a proprietary nutraceutical recovery drink on changes in performance, body composition, anabolic status, muscle damage, inflammation and oxidative stress over the course of a 7-week conditioning period immediately prior to preseason camp. At the beginning (trial 1) and end (trial 2) of a 7-week training phase, body composition, vertical jump and 225 lb bench press were assessed in Division I college football players (n ¼ 25). A 30 s Wingate Anaerobic Test plus eight 10 s intervals was used to examine power and biochemical responses. Blood samples were collected pre-, 0 and 60 min post-test for analysis of interleukin-6 (IL), 8-isoprostane (8-iso), cortisol (CORT) and resting testosterone:CORT (T:C) ratios. Athletes were randomly assigned to either an experimental group (EXP) receiving the nutraceutical drink (n ¼ 13) or a control group (CON) receiving an isocaloric equivalent (n ¼ 12). EXP had a significantly greater increase in peak power (P , 0.05) and significant decreases in percentage body fat and fat mass (P , 0.05). Multivariate ANOVA for repeated measures (RM MANOVA) revealed a significant test £ time £ group interaction (P , 0.05) for changes in CORT, IL-6 and 8-iso from trial 1 to trial 2. Follow-ups revealed no significant differences between groups at trial 1 for any of the variables. At trial 2, EXP had significantly lower CORT at rest (P ¼ 0.01) and 60 min post-test (P ¼ 0.001). Additionally, IL-6 was significantly different between EXP and CON at 0 (P , 0.01) and 60 min post-test (P , 0.01), with CON having an elevated IL-6 response. There were also differences in both 8-iso and creatine kinase at all time points at trial 2, with CON having higher levels (P , 0.02.). There were significant differences between groups in T:C ratio changes (P , 0.05), with EXP having an improved T:C ratio. It appears that supplementing the post-workout diet of Division I college football players with a nutraceutical recovery drink has favourable effects on body composition, peak power output and biochemical markers. Based on differences between groups that emerged at rest at trial 2, it appears that this supplement positively impacts both acute and chronic physiological responses indicative of improved recovery.
Keywords: antioxidant; ergogenic aids; anaerobic power; oxidative stress; hypothalamic–pituitary–adrenal axis; superoxide dismutase
The effects of a post-workout nutraceutical drink on body composition, performance and hormonal and biochemical responses in Division I college football, Comparative Exercise Physiology 6(2); 73–80 layers, SM Arent, P Davitt, DL Golem, CA Williams, KH McKeever and C Jaouhari

In a prospective study we tested the effect of oral supplementation of GliSODin (100% vegetable compound comprised of gliadin, a wheat protein extract bound to superoxide dismutase derived from cantaloupe) in reducing oxidative stress in rats subjected to γ-radiation. Adult male Swiss albino rats were used in this study, exposed to 6 Gy of γ-radiation and/or oral gavage with 5mg/ml/rat of GliSODin for 3 successive weeks. Oxidative stress biomarkers were evaluated in blood plasma, liver, kidney and spleen tissues. Some of the haematological parameters were investigated.
Histopathological observations in tissues were also detected. After γ-irradiation a significant decrease in haemoglobin (Hb)content,red blood cells RBCs count and haematocrite (Hct) level was recorded. Lipid peroxidation markers [malondialdehyde (MDA), lipid hydroperoxide (LHP) and conjugated diene (CD)] showed a significant increase. Histopathological examinations revealed a dangerous of alterations in liver, kidney and spleen tissues. However, GliSODin supplementation resulted in a significant decrease in lipid peroxidation either alone or after radiation exposure comparing to irradiated group. The antioxidant defence enzymes including superoxide dismutase (SOD), catalase (CAT) activities and reduced glutathione (GSH) content recorded a significant increase comparing to irradiated group. Histopathological examinations showed a melioration of radiation- induced damage. As a result, GliSODin could be considered a food supplement in the trials of minimizing oxidative stress disorders due to radiation exposure.
The efficacy of oral supplementation of GliSODin in reducing the Oxidative Stress in Rats Subjected to gamma-radiation, N. Hanafi and S.Z. Mansour and S.F. Salama

Abstract : High-level power-endurance are subjected to intense conditioning during preseason preparation in order to be able to sustain near-maximal efforts for extended periods. They often walk a fineline between optimal training and overtraining in an attempt to maximize sport-specific fitness.
Purpose: To examine changes in performance capacity and oxidative stress responses in college soccer players over the course of a 21-day preseason preparation and to determine the impact of supplementing with a formula consisting of a proprietary antioxidant and nutraceutical blend containing superoxide dismutase (SOD), CoQ10, and beta glucans purported to reduce oxidative stress and enhance functioning.
Methods: Male Division 1 college soccer players (N=22) performed a progressive maximal treadmill test at the beginning and end of preseason in order to access changes in velocity at lactate threshold (Vlt) and at onset of blood lactate accumulation (V obla), time to exhaustion, and lipid hydroperoxide (LPO) response. The test consisted of 3-minute stages run at a constant 1% grade. Speed was increased by two km-h1 per stage until exhaustion. Blood lactate was sampled via capillary puncture at the end of each stage. Plasma concentration of LPO was accessed before and after each test. Following baseline testing, athletes were randomly assigned to receive the supplement blend (EXP n=12) or an isocaloric equivalent (CON n=10) daily for the duration of the preseason training.
Results: Repeated measures MANOVA revealed significant changes in performance capacity and oxidative stress markers over the preseason (p max .001). Follow-ups indicated that ΔV LT (0.8+0.3 km-h1, p max .05), deltaV OBLA (1.1 +0.3 km-h-1, p max .01), and deltaTime to exhaustion (39.4 + 16.5 s, p max .05) were improved to across groups. There was a nearly significant group x time interaction with LPO response (p max .07). Examination of effect sizes (ES) and 95% CI indicated that EXP had a greater reduction in LPO responses during testing from preseason to end of preseason compared to CON (ES = -0.55). LPO responses were elevated in CON from pretest to posttest (ES = 0.78). EXP, when compared to CON, also appears to have a greater improvement to time until exhaustion. (ES = 0.39 and VLT (ES = 0.30)
Practical Application: Preseason training in male college soccer players resulted in significant improvements in performance capacity, as indicated by improved VLT, V OLBA, and time to exhaustion. In addition, though the short-term effects appear modest, supplementing the diet with a proprietary antioxidant/nutraceutical blend may enhance some of these effects, possibly by allowing for improved recovery.
Nutritional Supplement in Male College Soccer Players: Effects on Performances and Oxidative Stress, Shawn M. Arent, CSCS, David DiFabio, D John Greenwood, Joseph Pellegrino, Carey A. Williams – Rutgers University, New Brunswick, NJ

Based on our own investigations, as well as from those already performed by other teams, both in human and in experiments done in animal models, mostly in rats (wistar) and mice (balb c) , we can draw the conclusions regarding the dose ranging and the time necessary to observe an effect of glisodine® as follows:
1) From animal and human data, it can be deduced that the physiological effect of glisodine® on the prevention of exogenous induced oxidative stress depends on both length of administration and dosing. This means that the recommended dose has to take into account these two factors before observing an effect.
2) In healthy human studies, we have currently used a dose of 200 mg during one month or 500 mg during two weeks to observe an equivalent effect.
3) Although it is difficult to strictly compare animal and human dosing, we have made similar observation that low dose and long period results in a similar effect as higher dose in a shorter period.
4) Lastly for a used in patients we think that a higher dosing should be recommended (between 500 mg and 1 gram daily) for the beginning of the treatment (first two or three weeks) and then the normal dosing between 200 and 500 mg daily, in order to observe a quicker effect.
Statement from Pr Xavier Leverve on dose and time related effect in healthy human subjects, what can draw the conclusion regarding the dose ranging and time necessary to oibserve an effects of GliSODin - Inserm E-0221, Grenoble

Increased levels of serum IgE have been described in gliadin-intolerant patients; however, biological mechanisms implicated in this immunoglobulin production remained unknown. In this study, we demonstrated that in vitro crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE production by human peripheral blood mononuclear cells (PBMC), indicating that the biological process related to gliadin intolerance and/or allergy may lead to IgE production in vivo. It was found that crude gliadin and Glilys potentiated, after 13 days of culture in a dose-dependent manner, IL-4-induced IgE production and, to a lesser extent, the IgG production, while they did not affect IgA or IgM productions. This promoting effect of gliadin and Glilys on the IL-4-induced activation of normal human PBMC was also observed on the early release (2 days) of the soluble fraction of CD23, suggesting its possible involvement in IgE potentiation. The promoting effect of crude gliadin and Glilys appeared to be indirect because they did not modify purified B-Iymphocytes IgE production after IL-4 and anti-CD40 monoclonal antibody stimulation.
In addition, as revealed by luminol-dependent chemiluminescence, we demonstrated that crude gliadin and Glilys promoted a substantial production of free radicals by normal human PBMC, treated or not with IL-4. This redox imbalance associated with an increased IgE production led us to evaluate the effect of pharmacological antioxidants (N-acetyl-cysteine (NAC) and Cu/Zn­superoxide dismutase (SOD1)) on IgE production by human PBMC. The NAC and the intracellularly delivered SODI were found to suppress the IL-4 ± crude gliadin or Glilys-induced IgE production by normal human PBMC. Taken together, these data indicated that gliadin specifically enhanced IL-4-induced IgE production by normal human PBMC, probably by the regulation of redox pathways, and that this 'pro-allergenic' effect could be counteracted by natural antioxidants: thiols and/or vectorized SODl
Wheat gliadin promotes the interleukin 4 induced IgE production by normal human peripheral mononuclear cells through a redox-dependent mechanism, Cytokine 21, 2003, 270-280, Bernard Dugasa, Nathalie Dugas, Marc Conti, Alphonse Calenda, Paco Pino, Yolene Thomas, Dominique Mazier, Ioannis Vouldoukis

Si chacun aime s’exposer sous ses rayons, quelques précautions sont à prendre pour prévenir ses méfaits sur la peau. Appliquer une crème solaire toutes les deux heures ou encore ne s’exposer que lors des plages horaires recommandées sont des précautions connues. Depuis quelques années, la voie orale avec des compléments à base de caroténoïdes est également plébiscitée. Nouveauté à base de SOD de melon, l’antioxydant le plus puissant, la cure GliSODin® Esthétique Eclat de la Peau agit pour booster les crèmes solaires et mieux préparer la peau aux rayons du soleil et lutter contre ses dommages.
If everyone likes to expose themselves to the sun, some precautions must be taken to prevent their harm on the skin. Apply sunscreen or expose yourself only during the recommended time periods are known precautions. In recent years, the oral route with supplements based on carotenoids is also popular. New with SOD melon, the most powerful antioxidant, the GliSODin® better prepare the skin for the sun's rays and fight against its damage, and even works to boost sun creams.

Since the earliest beginning of Life, living organisms are continuously exposed to a major risk of oxidative damage, which is mostly related to oxygen. Other sources, such as light, radiations or chemicals, are also involved. The extreme toxicity of oxygen is related to its unique capacity of generating free radicals, which have long been recognized as harmful compounds on biological molecules. Actually, Life appeared before oxygen, since its early emergence resulted from a long period of microorganism and plant photosynthesis.
The increase in oxygen partial tension in earth atmosphere was extremely deleterious for all biological molecules and the massive contemporary vanishing of living species was related to oxygen toxicity. Among several antioxidant strategies developed though the process of Evolution, mitochondrion ancestors played probably a major role in adapting Life to survive to such massive oxidative stress.
Because of this long and mandatory metabolic evolution, a highly complex interaction between life (mitochondrial ATP synthesis) and death (oxidative toxicity) has been developed. The most harmful free radicals or reactive oxygen species (ROS) have in common a very short half-life indicating that they can very quickly exchange electrons with any kind of biological molecule. Therefore, these molecules are difficult to be directly evidenced in normal biological conditions and detection of oxidative stress is mostly achieved by assessing the result of this process: i.e. through the detection of damaged (oxidized) molecules (DNA, lipids, proteins etc.). On the other hand, the balance between pro and antioxidant activities is so finely tuned that any increase in antioxidant defense can be viewed either as the development of a good protection against oxidative stress or as an adapted response to previous oxidative damage. Hence an increase in the antioxidant defense indicates actually the result of an exposure to higher oxidative conditions. Therefore, assessing antioxidant capacity cannot be obtained by using a single parameter, whatever its intrinsic value and it is probably more informative to perform a dynamic assessment to a response of a given stress than a basal biological compound determination.
Oxidative stress and antioxidants: how to assess a risk or a prevention? Theoretical consideration and application to SOD-Gliadin, Professor Xavier Leverve, Laboratory of Fundamental and Applied Bioenergetics
INSERM U884 and University Joseph-Fourier, Grenoble, France

Dietary antioxidant supplementation has been commonly used by the Western society. Different supplements have been developed over the past years and research has been gathered both on animal and clinical research trials. In this review, orally administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated in respect to its therapeutic value. Critical examination of the effects of SODGliadin supplementation is carried out, especially pin-pointing its consequences on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD-Gliadin might have advantageous health effects. These are more or less relevant depending on the condition or pathology under consideration. Also, in general, authors support the use of SOD-Gliadin supplementation as a complementary treatment rather than a therapeutic one.
Oral supplementation with melon superoxide dismutase combined with wheat gliadin - Susana Romao - Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Switzerland

Background: Using specific antibodies against bovine Cu/Zn-superoxide dismutase (EC 1.15.1.1, SOD1) we demonstrated that anti-SOD antibodies (IgG1) are able to promote the intracellular translocation of the antioxidant enzyme. The transduction signalling mediated by IgG1 immune complexes are known to promote a concomitant production of superoxide and nitric oxide leading to the production of peroxynitrites and cell death by apoptosis. The Fcmediated intracellular delivery of SOD1 thus limited the endogenous production of superoxide. It was thus of interest to confirm that in the absence of superoxide anion, the production of nitric oxide protected cells against apoptosis. Study in greater detail clearly stated that under superoxide anion-free conditions, nitric oxide promoted the cell antioxidant armature and thus protected cells against redox-induced apoptosis.
Materials and Methods: The murine macrophage cell-lines J774 A1 were preactivated or not with interferon-! and were then stimulated by IgG1 immune complexes (IC), free SOD1 or SOD1 IC and superoxide anion, nitric oxide, peroxynitrite, and tumor necrosis factor-alpha (TNF-alpha) production was evaluated. The redox consequences of these activation processes were also evaluated on mitochondrial respiration and apoptosis as well as on the controlled expression of the cellular antioxidant armature.
Results: We demonstrated that SOD1 IC induced a Fc gamma receptor (FcgammaR)-dependent intracellular delivery of the antioxidant enzyme in IFN-gamma activated murine macrophages (the J774 A1 cell line). The concomitant stimulation of the FcgammaR and the translocation of the SOD1 in the cytoplasm of IFN-gamma-activated macrophages not only reduced the production of superoxide anion but also induced the expression of the inducible form of nitric oxide synthase (iNOS) and the related NO production. This inducing effect in the absence of superoxide anion production reduced mitochondrial damages and cell death by apoptosis and promoted the intracellular antioxidant armature.
Conclusions: To define the pharmacologic mechanism of action of bovine SOD1, we attempted to identify the second messengers that are induced by SOD1 IC. In this work, we propose that Fcmediated intracellular delivery of the SOD1 that reduced the production of superoxide anion and of peroxynitrite, promoted a NO-induced protective effect in inducing the antioxidant armature of the cells. Taken together, these data suggested that specific immune responses against antigenic SOD1 could promote the pharmacological properties of the antioxidant enzyme likely via a NO-dependent mechanism.
Fc-Receptor-Mediated Intracellular Delivery of Cu/Zn-superoxide Dismutase (SOD1) Protects Against Redox-Induced Apoptosis Through a Nitric Oxide Dependent Mechanism, Ioanis Vouldoukis, Virginie Sivan, Marie Catherine Vozenin, Caroline Kamaté, Alphonse Calenda, Dominique Mazier, and Bernard Dugas

To study the mutual interaction between physical exercise and antioxidant systems in rats, we selected swimming as a model for exercise performance. Swimming belongs to the natural behavior of a rat, which under proper experimental conditions, primarily involves physical exercise with little emotional arousal. Therefore, we developed a swimming basin in which the intensity of exercise was manipulated by swimming speed and swimming duration. A laser beam interruption system enables recording of swimming patterns. For comparison we also used the basin to induce emotional arousal. Hereto the basin was transformed into a maze, in which unexpected blockade of a learned swimming route induced a panic-like emotional reaction. The antioxidant enzyme superoxide dismutase decreased in rat plasma after emotional arousal, not after physical exercise. Depletion of the antioxidant glutathione in the liver by diethyl maleate led to decrease of swimming performance. Noradrenaline but not adrenaline plasma levels increased in response to physical exercise. After emotional arousal the ratio noradrenaline/adrenaline did not change. In contrast, lactate only increased in response to emotional arousal. Plasma levels of glucose increased after both stress situations. Beta-adrenoceptor function, determined in the heart and in erythrocytes, only changed after physical exercise. The sensitivity to the beta-agonist (-)isoprenaline in the right atrium decreased and a downregulation of the beta-adrenoceptor density was observed in the erythrocyte.
Control of physical exercise of rats in a swimming basin, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands, Kramer K , Dijkstra H, Bast A.

Scientists have discovered a natural ingredient derived from a species of melon that has been shown to reverse signs of atherosclerosis in aging blood vessel walls. This nutritional supplement is able to boost levels of the body’s most powerful antioxidant defense enzyme, superoxide dismutase (SOD). A comparison of two recently-published clinical trials shows that this natural supplement not only reversed signs of atherosclerosis in human blood vessel walls, but that it did so better than a leading multibillion dollar prescription statin drug. Just eight months ago, Life Extension members were enlightened to the ability of pomegranate to reverse signs of atherosclerosis. This specialized melon extract, together with pomegranate, offers aging humans a powerful new weapon in the battle to reduce the risk of heart attack and stroke by restoring healthy function to aging arteries.
Conclusion : Atherosclerosis is a serious threat to health. Its progression has been linked to increased risk of heart attack, stroke, atrial fibrillation and dementia, among other potentially fatal conditions. Since it may begin as early as childhood, and aging has been identified as the greatest risk factor for its development, it is vital to combat this arterial-dysfunction disease as early—and as aggressively—as possible. Nature has provided the means to protect ourselves from this insidious threat. By increasing our levels of the natural enzymatic antioxidant, superoxide dismutase (SOD), and by harnessing the potent polyphenol power of pomegranate, scientists have shown that it is now possible to help reverse the course of atherosclerosis—naturally.
Life extension report on GliSODin and Statins Atherosclerosis, LEF magazine, www.lef.org, By Dale Kiefer

‘Antioxidants’ are all individual in their properties; in their cellular compartmentalisation, in their ability to cross cell membranes, in the speed with which they undergo chemical reactions (kinetics), in their solubility, in their bioavailability, in their interactions with other molecules and in their ability to act as messengers, sending signals which initiate critical processes.
One of the most misunderstood topics in Nutritional Medicine is that of so-called ‘Antioxidants’. First, we looked at how ‘antioxidants’ are classified as Primary and Secondary and highlighted the differences between the typical ’antioxidant vitamins’ and the endogenous Antioxidant Enzymes such as Superoxide dismutase, Glutathione peroxidase and Catalase. Where typical ‘antioxidants’ such as vitamin C, E and beta-carotene are capable of quenching one free radical per antioxidant molecule, the Antioxidant Enzymes can quench several million free radicals per minute1. This little-known fact may help explain why so many clinical trials using ‘antioxidant’ vitamins have failed. What’s most exciting about the new understanding of the power of the Antioxidant Enzymes is that specific phytochemicals can ‘switch on’ that part of the DNA which codes for these and other cell-protective endogenous compounds. We are indeed on the cusp of a new paradigm in Nutritional Medicine as we use Nutrigenomics to optimise cellular function and cellular defences.
Antioxidants are not equal - time to rethink our strategies ? by Christine Houghton

IN GREEK MYTHOLOGY, the Chimera was a fearsome monster with the head of a lion, the body of a goat, and the tail of a serpent, which was slain by Bellerophon. In their paper (the current article in focus, Ref. 1, see p. L917 in this issue) on the construction of a chimeric superoxide dismutase (SOD), it appears that Gao et al. may have slain the monstrous task of constructing a therapeutically beneficial SOD. Since its discovery, the family of SODs has offered the potential for an effective antioxidant therapy that would reduce undesired consequences of inflammatory diseases as well as a number of conditions associated with uncontrolled overproduction of superoxide. However, for reasons that are not entirely clear, this goal has become somewhat of a monster for researchers. By constructing a chimera of two of the isotypes of SOD, Gao et al. may have achieved the construction of a therapeutically viable form of the enzyme.
The three SOD isomers, cytosolic Cu,Zn SOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular Cu,Zn SOD (SOD3), have been shown to have some therapeutic utility in protecting organ systems from oxidative stress, particularly in animal model systems of disease (5, 6). However, the success of these therapies has been limited due to a variety of reasons such as the short half-life of the protein in circulation, inability to associate with the cellular surface, and slow rates of equilibration between the vascular and interstitial spaces. Primarily due to the small molecular radius of SOD1 injected into circulation, it is rapidly (half-life of 10 min) cleared by the kidneys. Furthermore, its negative charge does not allow SOD1 to interact with cell surfaces and reduces its ability to enter the interstitium. Moreover, the therapeutic efficacy of SOD1 exhibits a bell-shaped curve after systemic administration, which, although not well understood, further limits the concentration of this protein that can be administered pharmacologically (5, 6). These limitations are partially alleviated by the use of SOD2, which is the least negatively charged SOD, and in the tetrameric form has a molecular radius of 40 Å, which retards its clearance by the kidneys (plasma half-life of 4 h). Despite its larger size, SOD2 equilibrates nearly four times faster that SOD1 within interstitial spaces (5).
SOD3 is normally tagged to the cellular surface via its hydrophilic positively charged “tail”, which gives the protein its heparin-binding ability (4, 8). Previously, it has been shown that cleavage of this tail results in the release of SOD3 from the cellular surface and that this loss may contribute to the sensitivity of the endothelium to oxidative insults. Furthermore, a major contributor of reactive intermediates near or at the endothelial plasma membrane is the NADPH oxidase. It is now recognized that a family of membrane-associated proteins (NOX) are responsible for generating superoxide and hydrogen peroxide in vascular endothelium and smooth muscle cells potentially for defense purposes and for cell signaling (9). The NOX enzymes appear to be composed of the typical low-potential membrane gp91phox flavoprotein that reduces oxygen to superoxide, as well as of cytosolic proteins, which in response to stimuli assemble into a functional oxidase (9). The generation of superoxide in the vascular compartment not only from activated inflammatory cells but also from vascular cells contributes to adverse effects of tissue injury during inflammation and other vascular disorders.
Therefore, adherence to the endothelium appears to be critical for the protective and anti-inflammatory function of SODs. The pharmacological efficacy of SOD2 may be limited by the inability of the protein to adhere to endothelial cell surface. For reasons not completely understood, SOD3 cannot be expressed and purified in large quantities, prompting investigators to utilize SOD1 and SOD2 primarily. However, on the basis of limitations of SOD1 and SOD2 discussed above, investigators have employed chemical and molecular approaches to generate SODs that combine some of the most beneficial features of SODs (2, 3). Examples of chemical modifications that extend the half-life of SOD1 and improve its pharmacological profile include coupling of polyethylene glycol, lecithin, putrescine, and sugars (for a review, see Ref. 6). Molecular approaches include the generation of chimeric proteins such as an SOD1/3 chimera protein that contains the positively charged tail of SOD3 and has been shown to be more effective in protecting tissues than SOD1 (3), although this chimera was still retained in the kidney and was not optimal for therapeutic utility.
To overcome these limitations, Gao et al. (1) have generated a new chimera utilizing the SOD3 COOH terminus linked to SOD2. This new protein combines the endothelial localization of SOD3 with the extended half-life and pharmacological profile of SOD2 to produce a novel bioactive agent against the negative effects of oxidative stress. Like the mythological Chimera, this new protein displays three different characteristics: it has the head of all SODs, namely the ability to remove superoxide; the body of a tetramer, such that its large molecular size reduces its clearance from the plasma; and the tail of positively charged residues, which allows it to be preferentially tagged to the endothelial surface. This novel chimeric protein shows considerable promise within two animal models of inflammation, IL-1-induced lung injury and carrageenan-injected paw inflammation. In the first model, administration of SOD2/3 chimera prevented the vascular leak and edema and reduced the number of infiltrating neutrophils in the lung after a IL-1 challenge. Similarly, SOD2/3 administration reduced the foot edema induced by injection of carrageenan. Thus through this novel strategy, Gao et al. (1) may have provided us with the appropriate strategy with which to utilize the power of SOD to combat oxidative stress induced by inflammatory disease. This major advancement coupled with the development of chemical and molecular approaches to target the chimeric protein to the lung (7) or other tissues could provide a powerful approach to generate a clinically therapeutic agent to fulfill the promise for SOD-based therapies.
Super-SOD: superoxide dismutase chimera fights off inflammation, American Journal of Physiology - Lung Cellular and Molecular PhysiologyPublished 1 June 2003 Vol. 284, no. 6, L915- L916, DOI: 10.1152/ ajplung. 00014. 2003

Investigation of oxidative stress in patients with alopecia areata and its relationship with disease severity, duration, recurrence and pattern.
Alopecia areata (AA) is an inflammatory autoimmune disease that causes hair loss on the scalp or trunk without scarring. Although the precise aetiopathogenesis of alopecia areata remains unknown, oxidative stress is thought to play a role. To investigate the relationship between severity and the role of oxidative stress in AA, by measuring plasma oxidant levels and antioxidant enzyme activities in erythrocytes.

Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice
Neuropeptide substance P (SP) and reactive oxygen species (ROS) have been demonstrated to play an important role in psychological stress-induced alteration of hair cycle, the underlying mechanism remains unknown. The present study aims to investigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronic psychological stress model) induced abnormal of hair cycle and induction of autophagy. Mouse CRS model was applied for 18 days with or without treatment antioxidant Tempol (a free radical scavenger) or SP receptor (NK1) antagonist (RP67580). After CRS procedure, hair growth cycle, oxidative stress markers and skin tissue autophagy levels were analyzed by ELISA or western blot. Our results revealed that CRS reduced body weight gain, distance of movement and times of standing, affected hair cycle by prolonging the telogen stage and delaying subsequent anagen and catagen stage. In addition, CRS resulted in increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase of autophagy markers (microtubule-associated proteins, light chain 3-II, LC3-II, and Beclin-1) in mice skin. Treatment with Tempol restored GSH-Px activity, and significantly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, as well as normalized hair cycle. In addition; RP67580 also restored SOD and GSH-Px activities, and markedly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, and normalized hair cycle. Our study provides the first strong evidence for SP and ROS play a role not only in alteration of hair cycle but also in induction of autophagy in psychological stress model, suggesting autophagy may contribute to psychological stress-induced abnormal of hair cycle.

Premature graying as a consequence of compromised antioxidant activity in hair bulb melanocytes and their
precursors.
Intricate coordinated mechanisms that govern the synchrony of hair growth and melanin synthesis remain largely unclear. These two events can be uncoupled in prematurely gray hair, probably due to oxidative insults that lead to the death of oxidative stress-sensitive melanocytes. In this study, we examined the gene expression profiles of middle (bulge) and lower (hair bulb) segments that had been micro-dissected from unpigmented and from normally pigmented hair follicles from the same donors using quantitative real-time RT-PCR (qPCR) arrays. We found a significant down-regulation of melanogenesis-related genes (TYR, TYRP1, MITF, PAX3, POMC) in unpigmented hair bulbs and of marker genes typical for melanocyte precursor cells (PAX3, SOX10, DCT) in unpigmented mid-segments compared with their pigmented analogues. qPCR, western blotting and spin trapping assays revealed that catalase protein expression and hydroxyl radical scavenging activities are strongly repressed in unpigmentedhair follicles. These data provide the first clear evidence that compromised antioxidant activity in gray hair follicles simultaneously affects maturehair bulb melanocytes and their immature precursor cells in the bulge region.

Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice.
Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown.
The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraintstress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle
Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation.

Oxidative stress in alopecia areata: a case-control study.
Increased reactive oxygen species (ROS) and lipid peroxidation are seen in many dermatologic disorders, including atopic dermatitis, psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris, and lichen planus. In alopecia areata (AA), there is increased production of ROSfrom perifollicular inflammatory cells.
The aim of this study was to determine the oxidative stress index (OSI) and lipid peroxidation by studying serum total oxidant capacity (TOC), total antioxidant capacity (TAC), and malondialdehyde (MDA) values in AA patients.
The demonstrated results confirmed the presence of oxidative stress and lipid peroxidation in AA. Whether these changes play a role in disease pathogenesis or result from the inflammatory process requires further investigation.

Low dose oxidative stress induces mitochondrial damage in hair cells.
Oxidative stress has been implicated as a cause of hair cell damage after ischemia reperfusion injury, noise trauma, and ototoxic injury. Oxidative stress can induce both apoptosis or necrosis depending on the degree of exposure. To study how reactive oxygen species (ROS) interacts with haircells, we have developed an in vitro model of oxidative stress using organ of Corti cultures exposed to physiologically relevant concentrations of hydrogen peroxide (H(2) O(2) ). Treatment of organ of Corti cultures with low concentrations of H(2) O(2) results in loss of outer hair cells in the basal turn of the explant. Higher concentrations of peroxide result in more extensive outer hair cell injury as well as loss of inner hair cells. Early outer haircell death appears to occur though apoptosis as demonstrated by staining of activated caspase. The effect of oxidative stress on mitochondrial function is a key determinant of degree of damage. Oxidative stress results in reduction of the mitochondrial membrane potential and reduction of mitochondrial produced antioxidants. Low doses of oxidative stress induce changes in mitochondrial gene expression and induce mitochondrial DNA deletions. Recurrent oxidative stress or inhibition of mitochondrial function significantly enhanced hair cell death. This tissue culture model of oxidative hair cell injury maintains a pattern of injury similar to what is observed in vivo after oxidative injury and can be used to study the effects ofROS on hair cells over the time period of the culture.

Lipid peroxidation/antioxidant activity in patients with alopecia areata
Aetiopathogenesis of alopecia areata (AA) is not fully understood and many factors have been assumed. Oxidant/antioxidant disequilibrium has been proposed with controversies between results.
The aim of this study was to determine lipid peroxidation/antioxidant activity in patients with AA and to determine its clinical significance.
  Increased lipid peroxidation and defective SOD activity exist in patients with AA. Addition of drugs with antioxidative effects seems to be valuable in treatment.

Evaluation of lipid peroxidation, oxidant/antioxidant status, and serum nitric oxide levels in alopecia areata.
The pathophysiology of alopecia areata (AA) has not been clearly defined; however, it appears as a tissue-restricted autoimmune disease mediated by T lymphocytes. Immunohistochemical studies have shown peri- and infra-follicular inflammatory infiltrate which damages hair follicles. We analyzed the role of lipid peroxidation and oxidant-antioxidant enzymes in the pathogenesis of AA.
Increased lipid peroxidation in AA may be related to an increase in NO level and XO activity and a decrease in SOD activity. These results suggest that lipid peroxidation and alterations in the oxidant-antioxidant enzymatic system may play a role in the pathogenesis.

Protective Effect of Superoxide Dismutase Against Hair Graying in a Mouse Model
Oxygen free radicals play a role in the aging process, and the protective effect of various antioxidants has been intensively studied, in particular for cutaneous aging. Besides hereditary factors, free radical-mediated damage to melanocytes of the hair follicle has been considered as a mechanism for aging of the hair. It was the aim of this study to evaluate the role of photosensitization reactions for hair graying and to demonstrate potential protective effects of superoxide dismutase (SOD). Mice with black hair were depilated with the fingertips on a surface of 6 × 2.5 cm on both sides of the dorsum. The right side received five applications of a SOD-containing gel before exposure to psoralen (concentration 0.5 mg/mL) plus UV-A (365 nm, 4 J/cm2). The left side was pretreated in the same way with a gel free of SOD. When the hair started growing again, the SODprotected side was covered with black hair, whereas the hair on the vehicle-treated side was gray or white in 27 of the 30 animals studied. The 0.01% SOD concentration was as protective as the 0.1% concentration. Heat-inactivated SOD, applied in another five animals, was not protective. Using fluorescent labeling of the SOD with fluorescein isothiocyanate, epifluorescence microscopy and digital imaging processing, we show that SOD applied to the skin surface penetrates through the follicular appendages, as well as through the unbroken stratum corneum. Our findings suggest that superoxide radicals, generated by interaction of UV-A light with the sensitizer, initiated the formation of secondary products with well-known DNA-damaging effects, such as lipid peroxidation products and tumor necrosis factor alpha. SOD prevented the damage to melanocyte DNA by dismutating superoxide. Photosensitization may be another mechanism for hair graying, which can be influenced by antioxidants. Given the large number of exogenous and endogenous sensitizers, this mechanism deserves further study for human hair graying.

Activation of macrophages leads to the secretion of cytokines and enzymes that shape the inflammatory response and increase metabolic processes. This, in turn, results in increased production of reactive oxygen species. The role of Cu/Zn superoxide dismutase (SOD-1), an important enzyme in cellular oxygen metabolism, was examined in activated peritoneal elicited macrophages (PEM) and in several inflammatory processes in vivo. LPS and TNF-α induced SOD-1 in PEM. SOD-1 induction by LPS was mainly via extracellular signal-regulated kinase-1 activation. Transgenic mice overexpressing SOD-1 demonstrated a significant increase in the release of TNF-α and of the metalloproteinases MMP-2 and MMP-9 from PEM. Disulfiram (DSF), an inhibitor of SOD-1, strongly inhibited the release of TNF-α, vascular endothelial growth factor, and MMP-2 and MMP-9 from cultured activated PEM. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. In vivo, transgenic mice overexpressing SOD-1 demonstrated a 4-fold increase in serum TNF-α levels and 2-fold stronger delayed-type hypersensitivity reaction as compared with control nontransgenic mice. Conversely, oral administration of DSF lowered TNF-α serum level by 4-fold, lowered the delayed-type hypersensitivity response in a dose-dependent manner, and significantly inhibited adjuvant arthritis in Lewis rats. The data suggest an important role for SOD-1 in inflammation, establish DSF as a potential inhibitor of inflammation, and raise the possibility that regulation of SOD-1 activity may be important in the treatment of immune-dependent pathologies.
We show that macrophage activators, such as LPS and TNF-α, increase SOD-1 in cultured PEM. All macrophages express the multicomponent enzyme, NADPH oxidase, and generate superoxides that are then dismutated by SOD-1 to various extents into hydrogen peroxide. LPS- and TNF-α-elicited macrophages display higher NADPH oxidase activity (9). Elevation of SOD-1 in macrophages has been previously demonstrated by oxidative stress induced by UVB radiation (25) or by hyperoxia and ischemia-reperfusion (26)
Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response - Moshe Marikovsky, Vered Ziv, Nava Nevo, Catherine Harris-Cerruti and Ori Mahler, J Immunol 2003; 170:2993-3001

The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide. There are three SODs: cytosolic copperzinc, mitochondrial manganese, and extracellular SODs. These enzymes have specific distributions and functions. Their importance in protecting lung tissue has been confirmed in transgenic and knockout animal studies. Relatively few studies have been conducted on these enzymes in the normal human lung or in human lung diseases. Most human studies suggest that there is induction of manganese SOD and, possibly, extracellular SOD during inflammatory, but not fibrotic, phases of parenchymal lung diseases and that both copperzinc SOD and manganese SOD may be downregulated in asthmatic airways. Many previous antioxidant therapies have been disappointing, but newly characterized SOD mimetics are being shown to protect against oxidantrelated lung disorders in animal models.
Superoxide dismutases in the lung and human lung diseases, Kinnula VL , Crapo JD

Purpose: The aim of this work was an evaluation of the influence of physical exercise in high-altitude conditions (about 2000 m above sea level) on thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) and catalase (CAT) activities in 10 kayakers and 10 rowers.
Methods: During their training, the sportsmen performed different kinds of static and dynamic efforts. The blood samples were taken from the cubital vein on the control day at low altitude and at high altitude, and on the 4th, 10th, and 18th days of the training camp before and after exercise. The TBARS and lactic acid concentrations in blood plasma and SOD and CAT activities in erythrocytes were measured.
Results: A statistically significant increase of SOD and CAT activities in erythrocytes after exercise on the 4th, 10th, and 18th days of training was found. The TBARS concentration in erythrocytes decreased in a statistically significant way after the end of the 10th day of exercise (P < 0.01), and on 18th day it more than doubled (P < 0.001) when preexercise values were compared with postexercise values of each day. A statistically significant increase of TBARS concentration in blood plasma was observed only after the end of exercise on the 10th day—using the same comparison as above. A statistically significant increased lactic acid concentration in blood plasma was noticed both on 4th or 18th days of training.
Conclusions: The results obtained show the increasing generation of oxygen-derived free radicals and the compensatory intensification of SOD and CAT activities after training in altitude (high mountain) conditions.
Effect of altitude training on the peroxidation and antioxidant enzymes in sportsmen, Wozniak, Alina; Drewa, Gerard; Chesy, Gabriel; Rakowski, Andrzej; Rozwodowska, Malgorzata; Olszewska, Dorota

Blood free radical antioxidant enzymes and lipid peroxides following long-distance and lactacidemic performances in highly trained aerobic and sprint athletes. Marzatico F1, Pansarasa O, Bertorelli L, Somenzini L, Della Valle G. Author information
OBJECTIVE: We have determined the differences of the influence of prolonged exercise or higher intensity lactacidemic exercise, on plasma lipid peroxidation and on erythrocyte antioxidant enzymatic defence system.
EXPERIMENTAL DESIGN: We measured plasma indices of lipid peroxidation, conjugated dienes (CD) and malondialdehyde (MDA) and erythrocyte enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT). The biochemical evaluations were performed in six healthy control males (C) and twelve athletes: six marathon runners (MR) and six sprint-trained athletes (STA) at rest and after a half-marathon (MR) and a training session of 6 x 150 m (STA).
RESULTS: In resting conditions MDA was higher in STA and MR than in C (p < 0.01), while only the MR showed significantly elevated levels of CD (p < 0.05). In STA the enzymatic scavenging capacity showed a significantly higher SOD (p < 0.01) and GSHPx (p < 0.01), while CAT was lower than in controls (p < 0.05). In MR only SOD (p < 0.01) was significantly higher than in C. It increased significantly immediately after half-marathon, while CAT decreased 24 and 48 hours postexercise respectively. In these athletes the lipoperoxidative indices increased in the early postexercise phase, while at 24 and 48 hrs both CD and MDA levels decreased. In STA enzyme activities were not modified by anaerobic performance while CD showed a peak 6 hrs postexercise and the MDA showed a progressive increase until 48 hrs afterwards.
CONCLUSIONS: Both strenuous long duration exercise and exhaustive sprint training overwhelm our capacity to detoxify ROS, producing oxidative stress. Thus an adequate supply of antioxidants could be appropriate.
Study for SOD