An unidentified inhibitor of lipid peroxidation in intestinal mucosa

Lipid peroxidation in vitro was tested by malonaldehyde production in gastrointestinal mucosa and compared with other tissues. It was observed that gastrointestinal mucosa was resistant to both non-enzymatic and enzymatic lipid peroxidation. This was due to the presence of an inhibitor of lipid peroxidation in the membranous fractions of intestinal mucosa. This inhibitor was capable of inhibiting other recognised peroxidation systems, such as liver mitochondria. This effect was confirmed by measurement of diene conjugation and utilisation of arachidonic acid as other markers of peroxidation, in addition to malonaldehyde production. Preliminary characterisation of this inhibitor revealed that it is resistant to proteolysis, non-diffusable and extractable from membranes by organic solvents. It was partially purified by methanol extraction of the mucosa and by three successive preparative thin-layer chromatography steps. The purified material gave a single spot on thin-layer chromatography, using a number of different solvent systems. Mobility of the inhibitor on thin-layer chromatography was different from that of authentic tocopherol, and it was present in the intestine of vitamin-E-deficient animals. These results suggest that the resistance of intestinal mucosa to lipid peroxidation is due to the presence of a novel inhibitor which is lipidic in nature.     

Sensitivity of mitochondria isolated from liver and kidney of rat and bovine to lipid peroxidation: A comparative study of light emission and fatty acid profiles

Much work has been carried out on non-enzymatic–induced lipid peroxidation of mitochondria obtained from different tissues of monogastric animals, but little information is available about this process in poligastric animals. Studies were carried out to determine the sensitivity of mitochondria isolated from liver and kidney of rat and bovine to lipid peroxidation (ascorbate-Fe²⁺ dependent) by comparison of light emission and fatty acid profiles. Mitochondria from both species were susceptible to lipid peroxidation. Measurements of chemiluminescence indicate that the lipid peroxidation process was more effective in mitochondria from rat liver than in the organelle obtained from bovine, whereas changes were not observed in mitochondria from rat and bovine kidney. The fatty acid composition of total lipids isolated from liver and kidney mitochondria of both species was substantially modified when subjected to non-enzymatic lipid peroxidation with a decrease of arachidonic and docosahexaenoic acids. The polyunsaturated fatty acid (PUFA) composition was higher in mitochondria obtained from rat liver (43.11± 4.16) than in bovine (15.78 ± 0.76). As a consequence, the unsaturation index (UI), was higher in mitochondria of rat liver than in bovine. Nevertheless, the PUFA composition of kidney mitochondria from both species was similar; therefore, statistically significant differences in the UI were not observed. The results suggest that mainly the PUFAs present in hepatic and kidney mitochondria were sensitive to oxidative damage. The lipid peroxidation process was more effective in rat liver mitochondria than in bovine. (Mol Cell Biochem xxx: 77–82, 2005) Member of Carrera del Investigador Científico, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)     

Selective effects of some anesthetics and detergents on lipid peroxidation of mouse heart homogenates.

1. The effects of some anesthetics and detergents on the Fe2+/ascorbate-stimulated non-enzymatic lipid peroxidation potential and on the NADPH-dependent enzymatic lipid peroxidation capacity were characterized in mouse heart homogenates. 2. Chlorpromazine turned out to be the most efficient inhibitor, causing a 50% inhibition at a concentration of 0.03 mM in the non-enzymatic assay, and at a concentration of 0.02 mM in the enzymatic assay. 3. Tetracaine was about a 10-times weaker inhibitor with IC50-values of 0.25 mM. High concentration of dibucaine (1 mM) exerted a 60% inhibition in the non-enzymatic assay, but lidocaine and procaine had no prominent effect with the concentrations used. 4. In the non-enzymatic, Fe(2+)-stimulated system, a 50% inhibition was obtained by using SDS, Triton X-100, and deoxycholic acid at concentrations of 0.004, 0.03, and 0.15%, respectively. 5. In the NADPH-dependent enzymatic lipid peroxidation system, corresponding concentrations were 0.02, 0.04 and 0.1%. Deoxycholate and Triton X-100 even stimulated (10-20%) the enzymatic lipid peroxidation at the lowest concentrations (0.005-0.01%). Saponin was the least effective of these detergents. 6. It is suggested that anesthetics and detergents induce structural rearrangements in the myocardiac membranes which result in the unavailability of phospholipid substrates to lipid peroxidation.     

Vitamin E dependent reduced glutathione inhibition of rat liver microsomal lipid peroxidation

Effects of reduced glutathione (GSH) were investigated on $\text{in}$$\text{vitro}$ lipid peroxidation of hepatic microsomes obtained from Long-Evans Hooded rats fed chemically defined, purified diets containing adequate or documented deficiencies of vitamin E (E), selenium (Se) or both. Glutathione inhibited lipid peroxidation mediated by both NADPH-dependent enzymatic and ascorbate-dependent non-enzymatic systems. The inhibitory effect of GSH was observed in microsomes obtained from E supplemented groups whereas it had no effect on microsomes from E deficient animals. Selenium status had no effect on GSH inhibition. Glutathione was found to be specific for the E dependent inhibition of lipid peroxidation and could not be substituted by other sulfhydryl compounds tested. Also, GSH did not inhibit non-enzymatic lipid peroxidation of heat-denatured microsomes from either E-supplemented groups or any of the other dietary regimens.     

Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north Indian population

The present study investigates in a experimental system in vitro the relationship between the non-enzymatic (ascorbate-Fe2+) and enzymatic (NADPH) lipid peroxidation in rat liver microsomes and nuclei. Chemiluminescence was measured as cpm/mg protein during 180 min at 37 degrees C. Approximately 50-55% of the fatty acids located in rat liver microsomes and nuclei are polyunsaturated with a prevalence of C18:2 n6 and C20:4 n6. The values of total light emission during the non-enzymatic and enzymatic lipid peroxidation were highest in microsomes than in nuclei. A significant decrease of C20:4 n6 and C22:6 n3 in rat liver microsomes and nuclei was observed during the lipid ascorbate-Fe2+-dependent peroxidation, whereas a significant decrease of C20:4 n6 in rat liver microsomes was observed during enzymatic lipid peroxidation. Over the time course studies, analysis of chemiluminescence in microsomes and nuclei demonstrated that the lipid peroxidation in the presence of ascorbate-Fe2+ reach a maximum at 50 and 30 min, respectively, whereas in the presence of NADPH it reachs a maximum at 20 min in both organelles. In liver microsomes and nuclei the peroxidizability index (pi) which indicates the degree of vulnerability to degradation of a selected membrane showed statistically significant differences between control versus ascorbate-Fe2+ when microsomes or nuclei were compared. Our results indicate that non-enzymatic (ascorbate-Fe2+) and enzymatic (NADPH) lipid peroxidation are operative in rat liver microsomes and nuclei but the sensitivities of both organelles to lipid peroxidation evidenced by chemiluminescence was greater in the presence of ascorbate-Fe2+ when compared with NADPH.     

Protein modification by Amadori and Maillard reactions during seed storage: roles of sugar hydrolysis and lipid peroxidation

The non-enzymatic modifications of proteins through Amadori and Maillard reactions play an important role in the loss of seed viability during storage. In the present study, the contribution of sugar hydrolysis and lipid peroxidation to Amadori and Maillard reactions, and to seed deterioration was investigated in mung-bean (Vigna radiata Wilczek). The contents of glucose and lipid peroxidation products in seed axes increased significantly during storage. The accumulation of Amadori products in seed axes was correlated to the lipid peroxidation, whereas the accumulation of Maillard products was closely correlated to sugar hydrolysis. The rate of accumulation of Maillard products was not well correlated to the content of Amadori products in both seed axes and protein/glucose model system, reflecting the complex nature of Amadori and Maillard reactions. The content of Amadori products in seed axes increased during the early stages of seed ageing, whereas the content of Maillard products increased steadily during the entire period of storage. The accumulation of Maillard products in seed axes was associated with the decline of seed vigour. These data suggest that, during seed ageing, sugar hydrolysis and lipid peroxidation are coupled with non-enzymatic protein modification through Amadori and Maillard reactions.     

Influence of Microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa

The objective of the present study was to evaluate the effects of microcystin-LR (MCLR) on the activity of membrane enzymes from intestinal mucosa. In addition, serum chemistry and peroxidative status of both serum and intestinal homogenate were evaluated after treatment with MCLR. Wistar rats were treated with intraperitoneal injection of either 100 microg pure MCLR/Kg body weight or saline solution. A significant increase in liver weight and altered serum enzyme activities were found in MCLR-treated rats, indicating damage to the liver in these rats, as previously suggested. A higher specific activity of sucrase (1.5-fold) was observed after the administration of MCLR, whereas other intestinal apical membrane enzymes, such as lactase, maltase and alkaline phosphatase were not modified by the treatment. The specific activities of acid phosphatase and succinate dehydrogenase, markers for lysosomal and mitochondrial membranes, respectively, were also increased (32% and 60%, respectively) in treated rats. The analysis of lipid peroxidation showed that the peroxidative status was increased in both serum and intestinal mucosa from MCLR-treated rats, reflecting an excess production of oxygen free radicals induced by this cyanobacterial toxin. In conclusion, this study shows that acute exposure to MCLR affects the intestinal physiology by modifying the intestinal peroxidation status as well as the activity of membrane enzymes.     

Enzymatic and non-enzymatic lipid peroxidation in leaf development.

Enzymatic and non-enzymatic lipid peroxidation has been implicated in programmed cell death, which is a major process of leaf senescence. To test this hypothesis we developed a high-performance liquid chromatography (HPLC) method for a simultaneous analysis of the major hydro(pero)xy polyenoic fatty acids. Quantities of lipid peroxidation products in leaves of different stages of development including natural senescence indicated a strong increase in the level of oxygenated polyenoic fatty acids (PUFAs) during the late stages of leaf senescence. Comprehensive structural elucidation of the oxygenation products by means of HPLC, gas chromatography/mass spectrometry and (1)H nuclear magnetic resonance suggested a non-enzymatic origin. However, in some cases a small share of specifically oxidized PUFAs was identified suggesting involvement of lipid peroxidizing enzymes. To inspect the possible role of enzymatic lipid peroxidation in leaf senescence, we analyzed the abundance of lipoxygenases (LOXs) in rosette leaves of Arabidopsis. LOXs and their product (9Z,11E,13S,15Z)-13-hydroperoxy-9,11,15-octadecatrienoic acid were exclusively detected in young green leaves. In contrast, in senescing leaves the specific LOX products were overlaid by large amounts of stereo-random lipid peroxidation products originating from non-enzymatic oxidation. These data indicate a limited contribution of LOXs to total lipid peroxidation, and a dominant role of non-enzymatic lipid peroxidation in late stages of leaf development.     

15-lipoxygenase-1: a prooxidant enzyme

Human and rabbit reticulocyte 15-lipoxygenase (15-lipoxygenase-1) and the leukocyte-type 12-lipoxygenases (12/15-lipoxygenases) of pig, beef, mouse and rat constitute a particular subfamily of mammalian lipoxygenases (reticulocyte-type lipoxygenases) with unique properties and functions. They catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and plasma lipoproteins. Moreover, they are a source of free radicals initiating non-enzymatic lipid peroxidation and other oxidative processes. Expression and activity of reticulocyte-type lipoxygenases are highly regulated. Moreover, the susceptibility of intracellular membranes toward these lipoxygenases is controlled and may be increased together with lipoxygenase activity under conditions of oxidative stress. Thus, oxidative stress may favor a concerted package of lipoxygenase-mediated enzymatic and non-enzymatic lipid peroxidation and co-oxidative processes. Reaction of reticulocyte-type lipoxygenases with low-density lipoprotein renders the latter atherogenic and appears to be involved in the formation of atherosclerotic lesions.     

Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats

Renal injury is considered as one of the prerequisites for calcium oxalate retention. In order to determine the role of lipid peroxidation related effects for hyperoxaluria, we evaluated the alterations in lipid peroxidation, antioxidants and oxalate synthesizing enzymes in lithogenic rats with response to vitamin E + selenium treatment. In kidney of lithogenic rats, the level of lipid peroxidation and the activities of oxalate synthesizing enzymes were found to be increased whereas the levels/activities of non-enzymatic and enzymatic antioxidants were found to be decreased. The urinary excretion of both oxalate and calcium were significantly elevated. Supplementation of lithogenic rats with vitamin E + selenium decreased the levels of lipid peroxides and the activities of oxalate synthesizing enzymes like glycolic acid oxidase (GAO), lactate dehydrogenase (LDH), xanthine oxidase (XO) with a concomitant increase in the activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and increased levels of non-enzymatic antioxidants like ascorbic acid, alpha-tocopherol and reduced glutathione (GSH). The urinary excretion of oxalate and calcium were normalized. The antioxidants vitamin E + selenium thereby protected from hyperoxaluria.     

Peroxidation stimulated by lipid hydroperoxides on bovine retinal pigment epithelium mitochondria: effect of cellular retinol-binding protein

This study analyzes the effect of cellular retinol-binding protein (CRBP), partially purified from retinal pigment epithelium (RPE) cytosol, on the non-enzymatic lipid peroxidation induced by fatty acid hydroperoxides of mitochondrial membranes isolated from bovine RPE. The effect of different amounts (50, 75 and 100 nmol) of linoleic acid hydroperoxide (LHP), arachidonic acid hydroperoxide (AHP) and docosahexaenoic acid hydroperoxide (DHP) on the lipid peroxidation of RPE mitochondria was studied; RPE mitochondria deprived of exogenously added hydroperoxide was utilized as control. The process was measured simultaneously by determining chemiluminescence as well as polyunsaturated fatty acid (PUFA) degradation of total lipids isolated from RPE mitochondria. The addition of hydroperoxides to RPE mitochondria produces a marked increase in light emission that was hydroperoxide concentration dependent. The highest value of activation was produced by LHP. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized RPE mitochondria incubated with and without hydroperoxides was found in the docosahexaenoic acid content, this decreased 40.90+/-3.01% in the peroxidized group compared to native RPE mitochondria. The decrease was significantly high: 86.32+/-2.57% when the lipid peroxidation was stimulated by 100 nmol of LHP. Inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (100-600 microg) of CRBP to RPE mitochondria. The inhibitory effect reaches the highest values in the presence of LHP.     

Interaction of lipid peroxidation products with nuclear macromolecules

The interaction of lipid peroxidation products with nuclear macromolecules was investigated in rat liver nuclei labelled with [3H]arachidonic acid. Lipid peroxidation reactions were driven both non-enzymatically and enzymatically by the addition of ascorbate-Fe2+ or NADPH-ADP-Fe3+, respectively, to the incubation mixtures. The extent of peroxidation was evaluated by the formation of thiobarbituric acid chromophore and of radioactive hydrophilic peroxidation products. The results obtained show that: (1) nuclear membrane lipid peroxidation products formed during incubation interact with DNA and total nuclear proteins; (2) non-enzymatic lipid peroxidation processes induced a 40% larger association of peroxidation products to DNA compared to processes driven enzymatically, whereas the corresponding interaction with total nuclear proteins was similar in both peroxidation systems; (3) the radioactivity associated with histones decreased during incubation in the presence of ascorbate-Fe2+ or NADPH-ADP-Fe3+, and increased in control samples (no additions); (4) inhibition of lipid peroxidation by the iron chelator Desferrioxamine B prevented the association of peroxidation products to nuclear macromolecules; (5) the levels of radioactivity found in DNA after 180 min of incubation would represent the formation of 0.6-1.0 adducts per 10(6) DNA bases. The results obtained provide evidence for an interaction between lipid peroxidation products and chromatin in the interior of the cell nucleus.     

Melatonin and N-acetyl serotonin inhibit selectively enzymatic and non-enzymatic lipid peroxidation of rat liver microsomes

Melatonin (N-acetyl-5-methoxytryptamine) and its immediate precursor N-acetyl serotonin in the metabolism of tryptophan are free radical scavengers that have been found to protect against non-enzymatic lipid peroxidation in many experimental models. By contrast, little is known about the antioxidant ability of these indoleamines against NADPH enzymatic lipid peroxidation. The light emission produced by rat-liver microsomes, expressed as total cpm during 180 min of incubation at 37 degrees C, was two-fold greater in the presence of ascorbate (0.4mM) when compared with NADPH (0.2 mM). Maximal peaks of light emission produced by microsomes lipid peroxidized with ascorbic-Fe(2+) or NADPH and expressed as cpm were 354,208 (at 60 min) and 135,800 (at 15 min), respectively. During non-enzymatic lipid peroxidation a decrease of total chemiluminescence (inhibition of lipid peroxidation) was observed when increasing concentrations of melatonin were added to liver microsomes. The protective effect was concentration-dependent. The inhibition observed in light emission was coincident with the protection of the most PUFAs. Preincubation of microsomes with N-acetyl serotonin reduced these changes very dramatically. Thus, in the presence of both antioxidants (0.36, 0.75, 1.5 mM), light emission percent inhibition during non-enzymatic (ascorbate-Fe(2+)) lipid peroxidation of rat liver microsomes was for melatonin: 6.12, 16.20, 34.88 and for N-acetyl serotonin: 85.10, 88.48, 84.4 respectively. The incubation of rat liver microsomes in the presence of NADPH (0.36, 0.75, 1.5 mM) produce a sudden increase of chemiluminescence that gradually increased and reached a maximal value at about 15 min; however, N-acetyl serotonin reduced these changes very efficiently.     

The oxidation of benzo[a]pyrene-7,8-dihydrodiol mediated by lipid peroxidation in the rat intestine and the effect of dietary lipids

This study has demonstrated that the microsomal fraction of the rat small intestinal mucosa has the capacity to catalyse the oxidation of benzo[a]pyrene(BP)-7,8-diol to BP-diol-epoxides (BPDEs) both by a mechanism involving the mixed-function oxidase system (NADPH-dependent) and as a result of the initiation of peroxidation of the membrane phospholipids by ferrous ions, ascorbate and ADP. The NADPH-dependent reaction was fastest in the proximal part of the intestine and resulted in the formation of approximately equal amounts of BPDE I and BPDE II. The lipid peroxidation-catalysed reaction favoured the production of BPDE I and was maximal in the middle region of the intestine, closely paralleling the rate of lipid peroxidation in the intestinal sections. Feeding rats on a cod liver oil diet, rich in C20:5 and C22:6, significantly increased the incorporation of these fatty acids into the microsomal fractions. This resulted in a greatly increased rate of lipid peroxidation in vitro and a significantly higher rate of lipid peroxidation-catalysed BP-7,8-diol oxidation compared to rats fed fat-free, mono-unsaturated lard or corn oil (58% C18:2) diets. Thus the rate of conversion of BP-7,8-diol to its ultimate carcinogenic forms during lipid peroxidation in the intestinal fractions of rats fed a polyunsaturated fat was quantitatively more important than the NADPH-catalysed reaction as measured in vitro.     

Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells

In aged rats, trophic hormone-stimulated testosterone secretion by isolated Leydig cells is greatly reduced. The current studies were initiated to establish a functional link between excess oxidative stress and the age-related decline in steroidogenesis. Highly purified Leydig cell preparations obtained from 5-month (young mature) and 24-month (old) Sprague-Dawley rats were employed to measure and compare levels of lipid peroxidation, non-enzymatic (alpha-tocopherol, ascorbic acid, and reduced/oxidized glutathione) and enzymatic (Cu, Zn-superoxide dismutase, Cu, Zn-SOD; Mn-superoxide dismutase, Mn-SOD; glutathione peroxidase-1, GPX-1, and catalase, CAT) anti-oxidants. The extent of lipid peroxidation (oxidative damage) in isolated membrane fractions was quantified by measuring the content of thiobarbituric acid-reactive substances (TBARS) under basal conditions, or in the presence of non-enzymatic or enzymatic pro-oxidants. Membrane preparations isolated from Leydig cells from old rats exhibited two- to three-fold enhancement of basal TBARS formation. However, aging had no significant effect on TBARS formation in response to either non-enzymatic or enzymatic pro-oxidants. Among the non-enzymatic anti-oxidants, the levels of reduced glutathione were drastically reduced during aging, while levels of alpha-tocopherol and ascorbic acid remained unchanged. Both steady-state mRNA levels and catalytic activities of Cu, Zn-SOD, Mn-SOD, and GPX-1 were also significantly lower in Leydig cells from 24-month-old rats as compared with 5-month-old control rats. In contrast, neither mRNA levels nor enzyme activity of catalase was sensitive to aging. From these data we conclude that aging is accompanied by reduced expression of key enzymatic and non-enzymatic anti-oxidants in Leydig cells leading to excessive oxidative stress and enhanced oxidative damage (lipid peroxidation). It is postulated that such excessive oxidative insult may contribute to the observed age-related decline in testosterone secretion by testicular Leydig cells.     

Antioxidant effect of anthocyanin on enzymatic and non-enzymatic lipid peroxidation.

In vitro enzymatic and non-enzymatic polyunsaturated fatty acid peroxidation was significantly inhibited in a dose dependent manner by purified anthocyanin, a deep-red colour pigment from carrot cell culture. The kinetics showed that anthocyanin is a non-competitive inhibitor of lipid peroxidation. Anthocyanin has been found to be a potent antioxidant compared to classical antioxidants such as butylated hydroxy anisole (BHA), butylated hydroxy toulene (BHT) and alpha tocopherol. This natural agent, in addition to imparting colour to the food, might prevent autooxidation of lipids as well as lipid peroxidation in biological systems.     

Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats.

The present study was designed to determine age-related changes in intestinal and hepatic antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation in male Wistar rats (n = 8) aged 2 wk, 2.5 mon, 5 mon, 10 mon, and 23 mon. In the small intestine, cytosolic SOD, GSH-PX activities and lipid peroxidation were not affected by age, but intestinal GST activity was noticeably enhanced as age increased. In particular, intestinal GST activity in 23 mon old rats was 3 times as strong as that in 2 wk old rats. In the liver, the activity of hepatic cytosolic SOD was not affected by age, whereas GSH-PX and GST activities in rats aged 10 mon and 23 mon were much stronger than those in rats aged 2 wk, 2.5 mon, and 5 mon. The increased lipid peroxidation in 2.5 mon and 5 mon old rats was observed when compared with that of other groups. It is therefore concluded from the results presented here that age greatly increases GST activity in the small intestinal mucosae and increasing GSH-PX, GST activities and lipid peroxidation in the liver from male Wistar rats.     

Lipid peroxidation: mechanisms, inhibition, and biological effects

In the last 50 years, lipid peroxidation has been the subject of extensive studies from the viewpoints of mechanisms, dynamics, product analysis, involvement in diseases, inhibition, and biological signaling. Lipids are oxidized by three distinct mechanisms; enzymatic oxidation, non-enzymatic, free radical-mediated oxidation, and non-enzymatic, non-radical oxidation. Each oxidation mechanism yields specific products. The oxidation of linoleates and cholesterol is discussed in some detail. The relative susceptibilities of lipids to oxidation depend on the reaction milieu as well as their inherent structure. Lipid hydroperoxides are formed as the major primary products, however they are substrates for various enzymes and they also undergo various secondary reactions. Phospholipid hydroperoxides, for example, are reduced to the corresponding hydroxides by selenoproteins in vivo. Various kinds of antioxidants with different functions inhibit lipid peroxidation and the deleterious effects caused by the lipid peroxidation products. Furthermore, the biological role of lipid peroxidation products has recently received a great deal of attention, but its physiological significance must be demonstrated in future studies.     

Changes in the activity of antioxidant enzymes and level of lipid peroxidation in the embryo brain tissue during prenatal action of ethanol]

Catalase, superoxide dismutase (SOD) activity and level of lipid peroxidation in embryo brain of 13-17-th day were evaluated during ethanol consumption by pregnant rats. The level of lipid peroxidation was more higher in alcohol groups, than in control groups. At the same time the reduced glutathione content was decreased by 13% in the brain of 15-th day embryos under the same conditions. One can draw a conclusion that the elevated level of lipid peroxidation may be a consequence of activated free radical mechanisms or consequence of reduced activity of a non-enzymatic antioxidant system.