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U okviru ovog diplomskog rada provedena su dva spektrofotometrijska istraživanja tri odabrane Micromeria vrste hrvatske flore – M. croatica, M. thymifolia i M. juliana. Prvo spektrofotometrijsko istraživanje koje smo proveli određivanje je sposobnosti hvatanja slobodnih radikala dušikovog (II) oksida u usporedbi s poredbenim otopinama aksorbinske i ružmarinske kiseline, te rutina. Sve tri Micromeria vrste pokazale su antioksidacijski potencijal (IC50 81,5-88,1 μg/ml), dok je M. croatica pri najnižoj koncentraciji (81,5 μg/ml) neutralizirala 50% slobodnih radikala. M. thymifolia ipak je neutralizirala preko 70% slobodnih radikala pri većim koncentracijama (400-1600 ug/ml). Drugo spektrofotometrijsko istraživanje koje smo proveli određivanje je sposobnosti inhibicije lipidne peroksidacije u usporedbi s poredbenim otopinoma rutina i ružmarinske kiseline. Sve tri Micromeria vrste pokazale su sposobnost inhibicije (IC50 54,5-206 μg/ml). Najveću antioksidacijsku sposobnost imala je M. croatica koja je već pri koncentraciji od 54,5 μg/ml neutralizirala 50% slobodnih radikala. Two spectrophotometrical researches of three Micromeria species of Croatian flora – M. croatica, M. thymifolia and M. juliana where examined in this thesis. First spectrophotometrical research we examined was capacity of inhibition of free NO(II) radicals compared to ascorbic acid, rosmarinic acid and rutin. All three Micromeria species expressed antioxidative capacity (IC50 81,5 – 88,1 μg/ml), while M. croatica had neutralized 50% of free radicals at lowest concentration (81,5 μg/ml). M. thymifolia had neutralized over 70% of free radicals at highest levels of concentration (400-1600 μg/ml). Second spectrophotometrical research we conducted was to determine capacity of inhibition of lipid peroxidation in comparison to rutin and rosmarinic acid. All three Micromeria species expressed antioxidative capacity (IC50 54,5-206 μg/ml). M. croatia had highest capacity of three examined species and had neutralized over 50% of free at concentration of 54,5 μg/ml.

Застосування кровоспинних джгутів є перевіреним засобом первинної медичної допомоги. Однак системні розлади, як і ультраструктурні, в зоні компресії можуть значно погіршити стан постраждалого організму. Встановлення ступеня пригнічення антиоксидантної системи в печінці є важливим аспектом розуміння перебігу ішемічно-реперфузійного синдрому кінцівки., The use of hemostatic tourniquet is a proved means of primary care. However, systemic disorders, as well as ultrastructural, in the area of compression can significantly worse the condition of the injured organism. Establishing the severity of antioxidant system depression in the liver is an important aspect of understanding the course of ischemic-reperfusion syndrome of the limb

Ozone application in a complex treatment of patients with diabetes complicated by pyoinflammatory processes has an apparent therapeutic effect and prevents the development of the relapse and complications of the disease promoting significant improvements of direct and remote results of treatment of the given pathology., Застосування озонотерапії в комплексному лікуванні хворих на ускладнений гнійно-запальними процесами перебіг цукрового діабету, має виражену лікувальну дію і запобігає розвитку рецидиву та ускладнень захворювання, що сприяє значному покращенню безпосередніх та віддалених результатів лікування даної патології., Применение озонотерапии в комплексном лечении больных сахарным диабетом с гнойно-воспалительными процесами, оказывает выраженное лечебное действие и предотвращает развитие рецидива и осложнений заболевания, что способствует значительному улучшению непосредственных и отдаленных результатов лечения данной патологии.

Bu çalışmada, kerevit yemine farklı oranlarda katılan n-3 serisi yağ asitlerinin pleopodal yumurta, hepatopankreas ve kas dokusunda (abdomen eti) malondialdehit (MDA) ve glutatyon (GSH) düzeylerine etkileri araştırıldı. Bu amaçla n-3 serisi yağ asidi içermeyen, toplam enerji düzeyi 3600 kcal/kg ve ham protein oranı %35 olan bir kontrol yemi (Deneme 1) hazırlandı. Bu yeme %1, 2 ve 3 oranlarında n-3 serisi yağ asidi ilave edilerek sırasıyla 2, 3 ve 4 nolu deneme yemleri oluşturuldu. Üç tekrarlı olarak yürütülen çalışmada, 107 günlük besleme sonunda, kerevitlerden pleopodal yumurta, hepatopankreas ve kas doku örnekleri alınarak, MDA ve GSH düzeyleri araştırıldı. Sonuçta; pleopodal yumurtaların MDA ve GSH düzeylerinde gruplar arasında önemli farklılıklar belirlendi (P, In this study, the effects of dietary n-3 series fatty acids on the malondialdehyde (MDA) and glutathione(GSH) levels in pleopodal egg, hepatopancreas and muscle of freshwater crayfish (Astacus leptodactylus) were investigated. For this aim, a control diet (D1) containing 3600 kcal/kg gross energy and 35% crude protein was prepared. The experiment was carried out with the three following treatments: control groups (D1, not supplemented n-3 series fatty acids), D2 (1%), D3 (2%) and D4 (3%). At the end of feeding for 107 days, MDA and GSH levels in pleopodal egg, hepatopancreas and muscle of crayfish were investigated. In conclusion, a significant difference in the level of MDA and GSH of pleopodal egg was determined between the experimental groups (P

INTRODUCTION: Emerging evidence indicates that nitric oxide (NO), which is increased in osteoarthritic (OA) cartilage, plays a role in 4-hydroxynonenal (HNE) generation through peroxynitrite formation. HNE is considered as the most reactive product of lipid peroxidation (LPO). We have previously reported that HNE levels in synovial fluids are more elevated in knees of OA patients compared to healthy individuals. We also demonstrated that HNE induces a panoply of inflammatory and catabolic mediators known for their implication in OA cartilage degradation. The aim of the present study was to investigate the ability of inducible NO synthase (iNOS) inhibitor, L-NIL (L-N6-(L-Iminoethyl)Lysine), to prevent HNE generation through NO inhibition in human OA chondrocytes. METHOD: Cells and cartilage explants were treated with or without either an NO generator (SIN or interleukin 1beta (IL-1β)) or HNE in absence or presence of L-NIL. Protein expression of both iNOS and free-radical-generating NOX subunit p47 (phox) were investigated by western blot. iNOS mRNA detection was measured by real-time RT-PCR. HNE production was analysed by ELISA, Western blot and immunohistochemistry. S-nitrosylated proteins were evaluated by Western Blot. Prostaglandin E2 (PGE2) and metalloproteinase 13 (MMP-13) levels as well as glutathione S-transferase (GST) activity were each assessed with commercial kits. NO release was determined using improved Griess method. Reactive oxygen species (ROS) generation was revealed using fluorescent microscopy with the use of commercial kits. RESULTS: L-NIL prevented IL-1β-induced NO release, iNOS expression at protein and mRNA levels, S-nitrosylated proteins and HNE in a dose dependent manner after 24h of incubation. Interestingly, we revealed that L-NIL abolished IL-1β-induced NOX component p47phox as well as ROS release. The HNE-induced PGE2 release and both cyclooxygenase-2 (COX-2) and MMP-13 expression were significantly reduced by L-NIL addition. Furthermore, L-NIL blocked the IL-1β induced inactivation of GST, an HNE-metabolizing enzyme. Also, L-NIL prevented HNE induced cell death at cytotoxic levels. CONCLUSION: Altogether, our findings support a beneficial effect of L-NIL in OA by preventing LPO process in NO-dependent and/or independent mechanisms., INTRODUCTION: De nouvelles données indiquent que l’oxyde nitrique (NO), que l’on retrouve en quantité accrue au niveau du cartilage de patients atteints d’ostéoarthrose (OA), joue un rôle dans la production de 4-hydrynonénal (HNE) via la formation de péroxynitrite (ONOO-). Le HNE est considéré comme étant un des produits les plus réactifs de la péroxidation lipidique (LPO). Notre laboratoire a rapporté des niveaux de HNE plus élevés que normal dans le liquide synovial provenant de genoux de patients OA comparativement aux sujets normaux. Nous avions aussi démontré que le HNE peut induire la production des médiateurs inflammatoires et cataboliques connus pour leurs implications dans la dégradation du cartilage dans l’OA. Le but de la présente étude est de vérifier si un inhibiteur sélectif pour la NO synthétase inductible (iNOS), soit le L-NIL (L-N6-(L-Iminoethyl)Lysine), peut empêcher la formation du HNE via l’inhibition de la production du NO dans des chondrocytes de patients OA. MÉTHODES: Les cellules ont été traitées soit avec ou sans un générateur du NO (SIN ou interleukine-1beta (IL-1β)) soit avec ou sans du HNE pendant 48 h en présence ou en absence du L-NIL. L’expression protéique de l’iNOS et de la sous-unité de la NADPH oxydase (NOX), la p47 (phox), a été vérifiée par Western blot. La génération du HNE a été révélée par ELISA, Western blot et immunohistochimie. Les niveaux de prostaglandine E2 (PGE2), gluthation-s-transférase (GST) et de la MMP-13 ont été mesurés par des kits commerciaux. La quantité de NO a été évaluée par la méthode de la réaction de Griess. La mesure des niveaux d'espèces réactives d’oxygène (ROS) a été effectuée par fluorescence en utilisant un kit commercial. RÉSULTATS: Le L-NIL inhibe la stimulation de la production de NO, de HNE ainsi que l’expression d’iNOS au niveau protéique et de l’ARNm par IL-1β. Le L-NIL bloque aussi la production de HNE indépendamment de la production de NO. La production des ROS et l’activation de p47 (phox) ont été inhibées par L-NIL. Fait intéressant, le L-NIL empêche la production de la PGE2, de la cyclooxygénase-2 (COX-2) et de la MMP-13 induite par le HNE. CONCLUSION: les résultats obtenus semblent démontrer l’effet bénéfique du L-NIL dans l’OA via la prévention de la production du HNE de manière dépendante ou indépendant du NO.

Le stress oxydant joue un rôle majeur dans le développement et l’évolution des maladies inflammatoires de l’intestin. Le corps humain est doté d’une panoplie d’enzymes antioxydantes ayant pour fonction de protéger l’intégrité cellulaire. De nouvelles enzymes au fort potentiel antioxydant, les paraoxonases (PON) 1, 2 et 3, ont récemment été identifiées tout au long du tube digestif, mais leurs rôles y restent inconnus. Les cellules intestinales Caco-2/15, qui ont la capacité de se différencier et d’acquérir les caractéristiques physiologiques de l'intestin grêle, ont été utilisées dans le présent travail pour étudier la régulation des PON. Les cellules ont été traitées avec différents effecteurs physiologiques (cytokines, LPS, stress oxydant) et pharmacologiques (fibrates, thiazolidinédiones) et l’expression des leurs gènes et protéines a été évaluée. Les résultats ont mis en lumière la modulation distincte de l’expression des PON par le stress oxydant et l’inflammation. Ceci suggère que chaque PON peut jouer un rôle différent au niveau intestinal et être impliquée dans le maintien de l’homéostasie. La régulation de l’expression des PON a également été largement explorée dans un article de revue. Pour définir le rôle de PON2, celle-ci étant potentiellement la plus importante pour l’homéostasie intestinale, les cellules Caco-2/15 ont été infectées à l’aide de lentivirus contenant des ARN d’interférence, ce qui a fortement réduit l’expression de PON2. En l’absence de PON2, les cellules Caco-2/15 étaient plus susceptibles face à un stress oxydant, la réponse inflammatoire était exacerbée et la perméabilité cellulaire paraissait altérée. Toutes ces composantes sont majeures dans le développement des maladies inflammatoires de l’intestin chez l’humain. De plus, des cellules Caco-2/15 de la PON2, ce qui a renforcé la force de la défense antioxydante cellulaire. Les résultats suggèrent que les PON jouent un rôle dans le maintien de l’homéostasie intestinale et pourraient être impliquées dans l’étiologie et la pathogenèse des maladies inflammatoires de l’intestin., Oxidative stress is a major part of the pathogenesis of inflammatory bowel disease (IBD). The endogenous antioxidative defence is formed of multiple enzymes that have to protect cellular integrity. Paraoxonases (PON1, 2 and 3) are antioxidant enzymes that have recently been identified throughout the digestive tract, but their roles remain unclear in the intestine. Intestinal Caco-2/15 cells, which have the capacity to differentiate and exhibit the functionality of the small intestine, were used to study PON’s regulation. Cells were treated with various physiological effectors (cytokines, lipopolysaccharides, oxidative stress) and pharmacological molecules (fibrates, thiazolidinediones) and gene and protein expression were determined. Results obtained showed that PONs are distinctly modulated especially by inflammation and oxidative stress and suggests that they could play different roles in the maintenance of intestinal homeostasis. PONs regulation has also been the main topic of a review article. Our results and the literature pointed to PON2 as the most important PON for intestinal health. To better define PON2 functions in the intestine, PON2 expression was knocked-down using lentiviral infection and plasmids containing anti-PON2 shRNA. In the relative absence of PON2, Caco-2/15 cells were more susceptible towards induction of oxidative stress, the inflammatory response was exacerbated and cell permeability seemed altered. All of these components are major players involved in the development of human IBD. Moreover, Caco-2/15 cells were treated with purified PON2, which increased their antioxidative defence. All of these results suggest that PONs are implicated in the antioxidative and anti-inflammatory response in intestinal epithelial cells and makes them potentially important players for the aetiology and pathogenesis of IBD.

У 120 женщин 18–45 лет, использующих комбинированные оральные контрацептивы (КОК), содержащие этинилэстрадиол (30 мкг) и дезогестрел (150 мкг) или этинилэстрадиол (30 мкг) и диеногест (2 мг), 12 циклов по 21 дню с 7-дневным перерывом, оценивали коагулопотенциал крови и липидпероксидацию (ЛПО) после каждого цикла. Оказалось, что КОК, содержащие этинилэстрадиол с прогестагеном третьего поколения повышают свертываемость крови, ускоряют ЛПО в крови и снижают ее антиоксидантную активность. Значительнее сдвиги при использовании диеногеста. Необходимо продолжить изучение механизмов этих сдвигов при гормональной контрацепции, сопоставляя эффекты известных гестагенов и используя для коррекции антиоксиданты. Blood coagulopotential and lipidperoxydation (LPO) after each cycle were estimated in 120 women of 18–45 years old who use combined oral contraceptivs (COCs) of ethinyl estradiol (30 mcg) and desogestrel (150 mcg), or ethinylestradiol (30 mg) and dienogest (2 mg) 12 cycles for 21 days with a 7-day break. It was found that COCs containing ethinylestradiol with a third-generation progestogen increase blood clotting accelerate LPO in the blood and reduce its antioxidant activity. Significant shifts are noticed in the use of SRI dienogest. It is necessary to continue to study the mechanisms of these shifts in the hormone contraception, comparing the effects of known progestogens and using antioxidants for the correction. Бышевский А.Ш., доктор медицинских наук, заслуженный изобретатель РФ, академик РАЕ и европейской академии естествознания, профессор кафедры биологической химии, Тюменская государственная медицинская академия, biochem@ tyumsma.ru Byshevsky A.Sh., Doctor of Medical Sciences (Grand MD), Honored Inventor of the Russian Federation, Member of Russian Academy of Natural Sciences and European Academy of Natural Sciences, Professor of Biochemistry Department, Tyumen State Medical Academy, biochem@tyumsma.ru. Полякова В.А., доктор медицинских наук, профессор, заведующая кафедрой акушерства и гинекологии, Тюменская государственная медицинская академия. Polyakova V.A., Doctor of Medical Sciences (Grand MD), Professor, Honored Doctor of Russian Federation, Head of Gynecology and Obstetrics Department, Tyumen State Medical Academy. Карпова И.А., кандидат медицинских наук, доцент кафедры акушерства и гинекологии, Тюменская государственная медицинская академия, karpovai.73@mail.ru Karpova I.A., Candidate of Medical Sciences (PhD), Professor of Gynecology and Obstetrics Department, Tyumen State Medical Academy, karpovai.73@ mail.ru. Винокурова Е.А., доктор медицинских наук, доцент кафедры акушерства и гинекологии, Тюменская государственная медицинская академия, vinokurovaelena@mail.ru Vinokurova E.A., Doctor of Medical Sciences (Grand MD), Associate Professor of Gynecology and Obstetrics Department, Tyumen State Medical Academy, vinokurovaelena@mail.ru. Хвощина Т.Н., аспирант кафедры акушерства и гинекологии, Тюменская государственная медицинская академия, karmafil@yandex.ru Hvoschina T.N., Post-graduate student of Gynecology and Obstetrics Department of Tyumen State Medical Academy, karmafil@yandex.ru. Сигильетова Т.С., аспирант кафедры акушерства и гинекологии, Тюменская государственная медицинская академия, tanushka_m86@ mail.ru Sigiletova T.S., Post-graduate student of Gynecology and Obstetrics Department, Tyumen State Medical Academy, tanushka_m86@mail.ru. Арабаджи О.А., аспирант кафедры акушер- ства и гинекологии, Тюменская государственная медицинская академия, aleks798279@mail.ru Arabadji O.A., Post-graduate student of Gynecology and Obstetrics Department, Tyumen State Medical Academy, aleks798279@mail.ru. Платицин В.А., кандидат медицинских наук, заведующий центральной научно-исследовательской лаборатории, Тюменская государственная медицинская академия, platisyn_v@mail.ru Platisin V.A., Candidate of Medical Sciences (PhD), Associate Professor of Therapy and Endocrinology Department, Head of the Central Reseach Laboratory, Tyumen State Medical Academy, platisyn_v@ mail.ru. Журавлева Т.Д., доктор биологических наук, старший научный сотрудник центральной научно- исследовательской лаборатории, Тюменская государственная медицинская академия. Zhuravleva T.D., Doctor of Biological Sciences (Grand ScD), Senior Researcher of the Ctntral Reseach Laboratory, Tyumen State Medical Academy. Тарасов Д.Б., аспирант кафедры гигиены с основами экологии, Тюменская государственная медицинская академия. Tarasov D.B., Post-graduate student of Hygene and Ecology Department, Tyumen State Medical Academy. Чернова А.М., ассистент кафедры акушерства и гинекологии, Тюменская государственная медицинская академия. Chernova A.M., Assistant at Gynecology and Obstetrics Department, Tyumen State Medical Academy.

OBJECTIF: Récemment, nous avons démontré que la modification du collagène type II (Col II) par le 4-hydroxynonénal (HNE), un produit de la peroxydation lipidique, est augmentée dans le cartilage arthrosique sans qu’on sache la signification de cette augmentation dans la pathogenèse de l’arthrose. L’objectif de cette étude vise à démontrer que cette modification affecte l’interaction chondrocytes/matrice extracellulaire (MEC) et en conséquence induit des changements phénotypiques et fonctionnels de ces cellules. METHODES: Des plaques de culture ont été préalablement cotées avec du Col II puis traitées avec du HNE (0.1-2 mM) excepté le puits contrôle. Les chondrocytes ont été ensuite ensemencés puis incubés pendant 48 heures. La viabilité des cellules est évaluée par le test MTT. Le Western blot est utilisé pour mesurer l’expression des molécules d’adhésion (l’ICAM-1 et l’intégrine α1β1), de la cyclooxygenase-2 (COX-2), du Col II ainsi que la phosphorylation de la p38 MAPK, ERK1/2 et NF-κB-p65. La RT-PCR en temps réel est utilisée pour mesurer l’expression de l’ARNm de l’ICAM-1, des intégrines α1β1, de la COX-2 et de la métalloprotéinases-13 (MMP-13). La détermination de l’expression de l’ICAM-1 à la surface des cellules est réalisée par cytométrie de flux. Des kits commerciaux ont servi pour mesurer le niveau de la MMP-13, de la prostaglandine E2 (PGE2), de l’activité de la caspase-8 et de la phosphorylation de la p38 MAPK, ERK1/2 et NF-κB-p65. RESULTATS: La modification du Col II par 0.2 mM HNE induit significativement l’expression des molécules d’adhésion telles que l’ICAM-1 et l’intégrine α1β1, de la MMP-13 sans avoir un effet sur la morphologie, la survie et le phénotype cellulaires. Nos résultats montrent aussi une forte augmentation de la phosphorylation de la p38 MAPK, d’ERK1/2 et de NF-κB-p65. Cependant, la modification du Col II par 2 mM HNE affecte la morphologie et la viabilité cellulaires et induit l’activité de la caspase-8. Elle inhibe fortement l’expression des integrines α1β1 et du Col II ainsi que la phosphorylation de l’ERK1/2 et de NF-κB-p65, mais par contre, induit significativement la production de la COX-2 et son produit la PGE2 ainsi que la phosphorylation de la p38 MAPK. Fait intéressant, le prétraitement des complexes HNE/Col II par 0.1 mM de carnosine empêche les changements phénotypiques et fonctionnels des chondrocytes. CONCLUSION : Ces nouveaux résultats suggèrent le rôle important de la modification du Col II par le HNE dans l’arthrose, en affectant le phénotype et le fonctionnement cellulaires des chondrocytes. La carnosine, par sa capacité de neutraliser le HNE, a révélé d’être un agent promoteur dans le traitement de l’arthrose., OBJECTIVE: The regulation of cell phenotype and function by the surrounding environment is deeply altered by the oxidative modifications of extracellular matrix (ECM) components that modify their structural and functional properties. This modification may be one cause involved in cartilage degradation in osteoarthritis (OA). Type II collagen (Col II) was reported to be targeted for 4-hydroxynonenal (HNE) binding, a very reactive product of lipid peroxydation. In the present study, we investigated whether HNE-binding to Col II affects OA chondrocytes phenotype and function and then, we determined the protective role of carnosine treatment in preventing these changes. METHODS: Isolated human OA chondrocytes were seeded in control wells and in HNE/Col II adducts-coated plates and incubated afterwards for 48 hours. Adhesion molecules at protein and mRNA levels were determined by Western blotting, flow cytometry and real-time RT-PCR. Commercial kits were used to evaluate cell death, caspase-8 activity and levels of prostaglandin E2 (PGE2), matrix metalloproteinase-13 (MMP-13), MAPK and NF-κB-p65. Col II, cyclooxygenase-2 (COX-2), MAPK and NF-κB-p65 levels were assessed by Western blotting. RESULTS: After 48 hours of incubation, the modification of Col II by 0.2 mM HNE induced strongly the expression of ICAM-1, integrin α1β1, MMP-13 and slightly COX-2 as well as PGE2 release without affecting cell morphology and viability as well as Col II expression. However, the modification of Col II with 2 mM HNE induced shape changes of cells from typical chondrocyte-like polygon shape to round semi-detached, affecting cells viability and inducing caspase-8 activity. It inhibited the expression of ICAM-1, integrin α1β1 and Col II, but in contrast, induced strongly PGE2 release and COX-2 expression. All these effects were prevented by 0.1 mM carnosine treatment, an HNE trapping drug. Carnosine was added to HNE-modified, Col II-coated plates 1h before cell seeding. Upon examination of different signalling pathways involved in these responses, we found that modified Col II with 2 mM HNE inhibited strongly the phosphorylation of ERK1/2 and NF-κB-p65 but induced strongly p38 MAPK. In contrast, the results indicated that MAPK and NF-κB-p65 were activated when cells were incubated with modified Col II by 0.2 mM HNE. CONCLUSION: The interaction between chondrocytes and collagen-bound HNE modulates different signalling pathways via adhesion molecules regulation and consequently leads to the expression of catabolic and inflammatory factors. Carnosine was shown to be an efficient HNE trapping agent able to counteract these effects.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

International audience; Oxylipins, derived from fatty acid hydroperoxides (FAHs), are thought to play different roles during plant pathogen interactions. During hypersensitive response (HR) some of them serve as signals necessary for defence gene activation whereas others could contribute to pathogen killing or could participate in the execution of plant programmed cell death (PCD) associated with this resistance. In order to address the role of these compounds in the latter process, we have closely observed lipid peroxidation, the first step of this metabolic pathway, under different situations which led either to accelerated or inhibited HR cell death. The oxidative process has been studied in cryptogein-elicited tobacco leaves and during Ralstonia solanacearum-induced HR. It was shown that FAH accumulation was preceded by the co-ordinated rise in 9 lipoxygenase (9 LOX) and galactolipase activities in addition to the transcription of a set of four genes encoding 9 LOX and patatin-like proteins, NtPAT1-3. The latter gene expression was at the origin of a metabolic pathway allowing the release of poly-unsaturated fatty acids from plastid galactolipids and their oxidation into free 9 FAHs. This 9 LOX-dependent lipid peroxidation was found to be sufficient to lead to HR cell death. Finally, during the bacterial-induced HR, lipid peroxidation appeared as a composite of metabolites of enzymatic and non-enzymatic origins and suggested the role of H2O2 as an important source of oxidant that might, in synergy with 9 FAHs, contribute to cell death execution.

In the present study, levels of malondialdehyde (MDA), end product of lipid peroxydation, and activity of catalase, a protective enzyme, in heart , kidney, liver and lung of guinea pigs born and bred in the altilude (Cullhuay, 3642 m), and another from sea level (La Molina, 238 m), were determined, in order to establish whether there exist any differences, and better understand of the oxydative stress in high altitude natives. Tissue levels of MDA were assessed by the n-methy-l-phenylindol method, and catalase enzyme activity was evaluated using the PURPALD colorimetric method. In tissue of heart, kidney, liver and lung of high altitude guinea pig were found MDA concentrations in mmoles/g protein: 0.309, 0.158, 0.133 and 0.257, values signifieantly higher in high altitude guinea pig than in those from sea level: 0.263, 0.115, 0.097 Y 0.201 (p < 0.05); and the value of catalase activity, expressed in mmoles of formaldehyde produced/g protein: 0.693, 0.268, 0.552 and 0.311, significantly lower in those from sea level:.784, 0.319, 0.628 and 0.377 (p < 0.05). These findings make evident an association between chronic hypoxia and increased generation of free radicals, and also that in chronic hypoxia diminishes the protective action of the antioxydative defense system, here represented by ea catalase enzyme. No significant correlations between catalase and MDA were found., Se evaluaron los niveles de malondialdehido (MDA) y la actividad de la catalasa en corazón, riñón, hígado y pulmón de cobayos nacidos y criados en la altura (Cullhuay, 3642 m), y un grupo similar a nivel del mar (La Molina, 238 m), con el fin de establecer si existen diferencias en las concentraciones y la actividad mencionadas entre los dos grupos, y comprender mejor el proceso del estrés oxidativo de los habitantes de las grandes alturas. Se determinó MDA usando el método del n- metil-1-fenilindol, y la actividad de la enzima catalasa por el método colorimétrico del PURPALD. En los tejidos de corazón, riñón, hígado y pulmón de cobayos de altura se obtuvo: concentraciones de MDA en mmoles/g proteína de: 0.309,0.158, 0.133 Y 0.257, valores significativamente mayores que a nivel del mar: 0.263, 0.115, 0.097 Y 0.201 (p < 0.05); y actividad de catalasa expresada en mmoles de formaldehído producido/g proteína de: 0.693, 0.268, 0.552 Y 0.311, valores significativamente menores que a nivel del mar: 0.784, 0.319, 0.628 Y 0.377 (p < 0.05). Estos hallazgos hacen evidente una asociación entre la hipoxia crónica y un incremento en la generación de radicales libres; así como que en la hipoxia crónica disminuye la acción protectora del sistema de defensa antioxidante, representado en este. estudio por la enzima catalasa. No se encontraron correlaciones significativas entre catalasa y MDA.