The effect of age and sex on glutathione reductase and glutathione peroxidase activities and on aerobic glutathione oxidation in rat liver homogenates

1. Changes in liver glutathione reductase and glutathione peroxidase activities in relation to age and sex of rats were measured. Oxidation of GSH was correlated with glutathione peroxidase activity. 2. Glutathione reductase activity in foetal rat liver was about 65% of the adult value. It increased to a value slightly higher than the adult one at about 2-3 days, decreased until about 16 days and then rose after weaning to a maximum at about 31 days, finally reaching adult values at about 45 days old. 3. Weaning rats on to an artificial rat-milk diet prevented the rise in glutathione reductase activity associated with weaning on to the usual diet high in carbohydrate. 4. In male rats glutathione peroxidase activity in the liver increased steadily up to adult values. There were no differences between male and female rats until sexual maturity, when, in females, the activity increased abruptly to an adult value that was about 80% higher than that in males. 5. The rate of GSH oxidation in rat liver homogenates increased steadily from 3 days until maturity, when the rate of oxidation was about 50% higher in female than in male liver. 6. In the liver a positive correlation between glutathione peroxidase activity and GSH oxidation was found. 7. It is suggested that the coupled oxidation-reduction through glutathione reductase and glutathione peroxidase is important for determining the redox state of glutathione and of NADP, and also for controlling the degradation of hydroperoxides. 8. Changes in glutathione reductase and glutathione peroxidase activities are discussed in relation to the redox state of glutathione and NADP and to their effects on the concentration of free CoA in rat liver and its possible action on ketogenesis and lipogenesis.     

Changes in the density of peripheral benzodiazepine binding sites in genital organs of the female rat during the oestrous cycle

The affinity and the density of peripheral-type benzodiazepine binding sites (PBzS) in tissues from the genital organs of female rats were studied during the oestrous cycle. When comparing PBzS density on the day of oestrus to PBzS density on the day of pro-oestrus, a significant increase was observed in the ovary (1.9-fold), oviduct (2.4-fold) and uterus (1.7-fold), but not in the kidney. Serum oestradiol also increased to a maximum on the day of pro-oestrus. The ovarian and uterine PBzS density and serum concentrations of oestradiol and progesterone were measured every 8 h between the days of dioestrus and pro-oestrus. Ovarian and uterine PBzS density increased to a maximal value at 01:00 and 09:00 h, respectively, on the day of pro-oestrus. However, a significant increase in PBzS density occurred in the ovary (P less than 0.02) and uterus (P less than 0.001) at 09:00 h on the day of pro-oestrus as compared to 09:00 h on the day of dioestrus. These changes were associated with an increase in serum oestradiol and progesterone concentrations. The affinity of PBzS in all tissues examined remained unaltered during the oestrous cycle. This study demonstrates that changes associated with the oestrous cycle occur in the density of PBzS in various genital organs.     

Effect of gender differences and voluntary exercise on antioxidant capacity in rats

The effects of gender difference and voluntary exercise on antioxidant capacity in rats were evaluated. The subjects were divided into two groups, physically active and sedentary. In the sedentary group, the level of hydroxyl radical in the liver was higher (P<0.001) in male rats than in female rats, however, in the physically active group, the level in male rats was lower (P<0.05) than in female rats. The levels of reduced glutathione (GSH) in physically active males and females were higher compared to those in the sedentary group. The physically active group also showed an increase in antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase activities. The level of liver GSH was higher in physically active females than in physically active males. For both groups, GPx and GR activities in females were significantly higher than in males. These results indicate that female rats have an intrinsically higher antioxidant capacity, which resulted in increased levels of GSH via the glutathione redox cycle and gamma-glutamyl cycle enzymes. The adaptation to altered antioxidant capacity, induced by physical activity, appeared to be affected by gender differences.     

Effect of exogenous progesterone on 17 beta estradiol secretion in 4-day cyclic rats]

The rate of ovarian 17 beta oestradiol was showed to be decreased on the decreased on the afternoon of dioestrus 2 in 4-day cyclic female rats with cycles prolonged to 5 days following progesterone treatment as compared to untreated 4-day cyclic females. OEstradiol values also appeared lower on dioestrus 3 and prooestrus in experimental 5-day cycles than, on prooestrus, in natural 4-day cycles.     

Plasma binding of oestradiol in progesterone-treated rats

Progesterone treatment of female rats causes an increase in body weight possibly via suppression of oestradiol secretion. This study was carried out to investigate the effect of progesterone on the non-protein bound and hence presumably biologically active fraction of oestradiol. Oestradiol binding to plasma proteins was studied in female Wistar rats during the oestrous cycle and after 12 days of treatment with progesterone (5 mg/day). There was no change in either the unbound fraction of oestradiol or plasma albumin concentrations during the oestrous cycle. Plasma oestradiol concentrations in progesterone-treated rats were similar to those seen during dioestrus, as were the degree of oestrogen binding and the plasma albumin concentrations. Although it was not feasible to calculate unbound concentrations, these results suggest that the increased body weight seen in progesterone-treated rats, and also during pregnancy, may be a result of suppression of unbound oestradiol concentrations to levels similar to those occurring during dioestrus.     

The response of rat liver lipid peroxidation, antioxidant enzyme activities and glutathione concentration to the thyroid hormone.

1. In liver microsomes from hyperthyroid rats NADPH-dependent lipid peroxidation induces a hydroperoxide formation 56% higher than that in euthyroid ones. 2. The addition of 5 microM Fe2+ (or Fe3+) strongly decreases the hydroperoxide level in favour of that of TBA-reactive substances. Higher iron concentrations (30 microM) have no significant effect. 3. In hepatocytes from hyperthyroid rats CCl4-induced lipid peroxidation produces an amount of TBA-reactive substances four times higher than that in those from euthyroid rats. 4. In the liver of hyperthyroid rats a GSH concentration decrease (by about 35%) is found while the opposite occurs in the blood of the same animals where GSH increases 2.5 times. 5. It is shown that in the liver of hyperthyroid rats, besides higher lipid peroxidation, a more active defense mechanism is operating since both glutathione peroxidase and glutathione reductase specific activities are higher than in euthyroid rats.     

Ontogenic changes in metabolism and transport of glutathione in the rat

Changes in the level of glutathione (GSH), the turnover rate, and gamma-glutamyltransferase (GGT) activity were examined in newborn, weanling, and adult male Wistar rats, the objective being to elucidate the mechanisms which control the hepatic GSH level during maturation as well as under conditions of different degrees of protein ingestion. The hepatic GGT activity in the newborn rats was high at birth, decreased within a few days to 1 to 2% of the initial level, and remained unchanged thereafter, when these rats were fed a normal diet after 3 weeks of age. In contrast, the hepatic GSH level increased 3-4-fold while total GGT activity in the kidney increased 6-8-fold. When weanling rats were fed a low protein diet (containing 10% soy protein) for 3 weeks, the hepatic GSH level decreased markedly while the GGT activity increased 5-6-fold. The turnover rate of hepatic GSH also increased, as determined by the use of buthionine sulfoximine, a specific inhibitor of GSH synthesis; a value of 2.1 h was obtained in comparison with 3.5 h for that of rats fed the normal laboratory chow (CRF-1). On the other hand, feeding adult rats on the low protein diet resulted in a marked decrease in hepatic GSH level with no effect on either hepatic or renal GGT activity. These results together with other observations may suggest that GSH translocated out of liver cells in the newborn rats is degraded mainly by these cells, while the tripeptide secreted by hepatocytes of adult rats is metabolized predominantly in extrahepatic tissues, such as the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)     

gamma-Butyrobetaine hydroxylase and the protective role of glutathione peroxidase

The selenoenzyme glutathione peroxidase in the presence of GSH effectively replaced catalase in the in vitro assay for gamma-butyrobetaine hydroxylase. Quantitatively, glutathione peroxidase was an order of magnitude more efficient than catalase, with maximal activity at less than 0.1 microM glutathione peroxidase in a standard reaction. Glutathione peroxidase prevented the loss of gamma-butyrobetaine hydroxylase during preliminary incubation with ferrous ions but without other substrates as well as in the course of the reaction. Regardless of whether glutathione peroxidase or catalase was present in the assay, the ascorbate concentrations needed to achieve half-maximal rates were similar (about 1 mM). Phosphate stimulated the rate of L-carnitine synthesis. Ferrous ion saturation indicated a pronounced effect of phosphate on the maximal velocity of the enzyme-catalyzed reaction, but its mechanism of action remains to be elucidated. Based on the subcellular distribution of gamma-butyrobetaine hydroxylase, catalase, and glutathione peroxidase, the role of glutathione peroxidase assumes importance. However, initial studies indicated that the assayable activity of liver gamma-butyrobetaine hydroxylase and L-carnitine concentrations in liver, blood plasma, and muscle were not significantly altered in selenium-deficient rats.     

Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats

Oxidative stress may contribute to epileptogenicity in genetic models of epilepsy. To address this, we examined the enzymatic activity of cytosolic Cu/Zn superoxide dismutase (SOD-1), mitochondrial Mn superoxide dismutase (SOD-2), and glutathione peroxidase (GPx) in the developing hippocampus of genetically epilepsy-prone rats (GEPR-9s). We also measured changes in the GSH/GSSG ratio, lipid peroxidation, and protein oxidation at post-natal days (PD) 7, 30, and 90, respectively. Compared with control Sprague-Dawley (SD) rats, GEPR-9s showed similar SOD-1 and SOD-2 activity but lower GPx activity. Epilepsy-prone rats also showed lower GSH/GSSG ratios than controls, and more lipid peroxidation (as measured by malondialdehyde levels) and protein oxidation (as measured by carbonyl levels). Treatment with kainic acid (KA) resulted in more pronounced seizures, less GPx activity, and lower GSH/GSSG ratios in GEPR-9s than in controls, but KA did not significantly affect SOD-1 or SOD-2 activity, suggesting that GEPR-9s do not compensate for reduced GPx activity by increasing SOD. Moreover, KA treatment resulted in significantly a lower GSH/GSSG ratio and GPx-like immunoreactivity and higher malondialdehyde and carbonyl levels in GEPR-9s than in controls. These findings were more evident in GEPR-9s at PD 90 than at PD 30, indicating that oxidative stress is age-dependent. Double-labeling immunocytochemical analysis demonstrated co-localization of GPx-immunoreactive glia-like cells and reactive astrocytes, as labeled by glial fibrillary acidic protein (GFAP). This suggests that mobilization of astroglial cells for synthesis of GPx protein is a response to KA insult, intended to decrease the neurotoxicity induced by peroxides. These responses were more pronounced in control SD rats than in GEPR-9s. Our results suggest that impairment of the GPx (including glutathione)-mediated antioxidant system contributed to epileptogenesis in GEPR-9s.     

Oxidized glutathione fermentation using Saccharomyces cerevisiae engineered for glutathione metabolism

Glutathione is a valuable tripeptide that is widely used in the pharmaceutical, food, and cosmetic industries. Intracellular glutathione exists in two forms, reduced glutathione (GSH) and oxidized glutathione (GSSG). Most of the glutathione produced by fermentation using yeast is in the GSH form because intracellular GSH concentration is higher than GSSG concentration. However, the stability of GSSG is higher than GSH, which makes GSSG more advantageous for industrial production and storage after extraction. In this study, an oxidized glutathione fermentation method using Saccharomyces cerevisiae was developed by following three metabolic engineering steps. First, over-expression of the glutathione peroxidase 3 (GPX3) gene increased the GSSG content better than over-expression of other identified peroxidase (GPX1 or GPX2) genes. Second, the increase in GSSG brought about by GPX3 over-expression was enhanced by the over-expression of the GSH1/GSH2 genes because of an increase in the total glutathione (GSH + GSSG) content. Finally, after deleting the glutathione reductase (GLR1) gene, the resulting GPX3/GSH1/GSH2 over-expressing ΔGLR1 strain yielded 7.3-fold more GSSG compared with the parental strain without a decrease in cell growth. Furthermore, use of this strain also resulted in an enhancement of up to 1.6-fold of the total glutathione content compared with the GSH1/GSH2 over-expressing strain. These results indicate that the increase in the oxidized glutathione content helps to improve the stability and total productivity of glutathione.     

The influence of dietary selenium and vitamin E on glutathione peroxidase and glutathione in the rat

The effect of dietary selenium (Se) and vitamin E supplementation on tissue reduced glutathione (GSH) and glutathione peroxidase activity has been studied in the rat. Increasing Se intake by 0.4 ppm gave significantly higher enzyme levels in all tissues studied, an effect not influenced by vitamin E intake. Further increasing Se to 4 ppm gave higher enzyme levels in red blood cells only, while in liver was there was a significant decrease in enzyme activity probably reflecting Se hepatotoxicity. In the absence of Se supplements increasing dietary vitamin E to 100 mg/kg diet significantly increased enzyme activity but this effect was modified by simultaneous Se supplementation.Se intake had no effect on GSH levels. Rats on high vitamin E intake 500 mg/kg had a significantly higher tissue GSH level. Dietary Se had a sparing effect on vitamin E, rats supplemented with Se having significantly raised plasma vitamin E levels.These results confirm the role of selenium in glutathione peroxidase and also show that vitamin E influences the activity of the enzyme.     

Schistosoma mansoni: influence of the female parasite on glutathione biosynthesis in the male

The glutathione (GSH) content of male Schistosoma mansoni increases in the absence of the female. This phenomenon, originally observed in vitro, also occurs within the host. At the time of recovery from mice, the GSH content of males from single-sex infections was 1.7-fold higher than that of paired males from mixed sex infections (P less than 0.01). The effect of mating status on male GSH biosynthetic and turnover rates was examined to determine the basis for increased GSH content in unpaired males. GSH turnover rates, measured when GSH biosynthesis was inhibited by greater than 95% with 5.0 mM DL-buthionine-SR-sulfoximine, were indistinguishable between unpaired and paired males with a first-order rate constant of 0.018 hr-1. In contrast, incorporation of L-[35S]cysteine into GSH revealed that GSH biosynthesis was 5-fold higher in unpaired than in paired males. Transport of L-cystine into male schistosomes, the presumed rate-limiting step in GSH biosynthesis, was unaffected by mating status. The GSH content increased when males were incubated in medium that had previously contained females or when separated from females by a microporous membrane. Males paired to 50% ethanol-fixed females had unchanged GSH content in vitro. It appears that male GSH biosynthesis may be regulated by a response stimulated by the female's physical presence in the gynechophoral canal and not by a soluble factor released from the female.     

Effects of gonadectomy and steroid treatment on renal prostaglandin 9-ketoreductase activity in the rat

The effect of gonadectomy and treatment with sex-steroids on renal prostaglandin 9-ketoreductase activity in 10-11 week old male and female rats was determined. Rats were gonadectomized or subjected to sham operation at 3 weeks of age. During week 7, rats were injected s.c. twice over a 6-day interval with vehicle (peanut oil, 0.5 ml X kg-1) or with depot forms of testosterone (5 mg X kg-1), estradiol (0.02 mg X kg-1), progesterone (5 mg X kg-1), or estradiol and progesterone combined. Renal prostaglandin 9-ketoreductase activity was about 50% higher in female rats than in males. Gonadectomy decreased 9-ketoreductase activity in females, but not in males, and eliminated the gender difference in enzyme activity. Treatment with estradiol elevated 9-ketoreductase activity in males and females, while treatment with testosterone or progesterone was without effect. Progesterone did, however, antagonize the elevation in 9-ketoreductase activity produced by estradiol.     

Inhibition of glutathione disulfide reductase by glutathione

Rat-liver glutathione disulfide reductase is significantly inhibited by physiological concentrations of the product, glutathione. GSH is a noncompetitive inhibitor against GSSG and an uncompetitive inhibitor against NADPH at saturating concentrations of the fixed substrate. In both cases, the inhibition by GSH is parabolic, consistent with the requirement for 2 eq. of GSH in the reverse reaction. The inhibition of GSSG reduction by physiological levels of the product, GSH, would result in a significantly more oxidizing intracellular environment than would be realized in the absence of inhibition. Considering inhibition by the high intracellular concentration of GSH, the steady-state concentration of GSSG required to maintain a basal glutathione peroxidase flux of 300 nmol/min/g in rat liver is estimated at 8-9 microM, about 1000-fold higher than the concentration of GSSG predicted from the equilibrium constant for glutathione reductase. The kinetic properties of glutathione reductase also provide a rationale for the increased glutathione (GSSG) efflux observed when cells are exposed to oxidative stress. The resulting decrease in intracellular GSH relieves the noncompetitive inhibition of glutathione reductase and results in an increased capacity (Vmax) and decreased Km for GSSG.     

Age- and sex-related differences in lipid peroxidation of mouse cardiac and skeletal muscles

1. The purpose of the present study was to characterize age- and sex-related changes in lipid peroxidation capacities and enzymatic antioxidants of cardiac and skeletal muscles in NMRI-mice (Mus musculus). 2. Lipid peroxidation rates (unstimulated and enzymatic/iron-stimulated) strongly decreased in skeletal muscle during ageing. 3. Unstimulated lipid peroxidation rate but not that of stimulated, also decreased in cardiac muscle. 4. The total level of Fe2+/ascorbate-stimulated non-enzymatic lipid peroxidation was not, however, affected by ageing. 5. The activity of catalase slightly increased in cardiac muscle and that of glutathione peroxidase in skeletal muscle during ageing. 6. Unstimulated lipid peroxidation rate was significantly higher in the skeletal muscle of male than female mice. 7. Correspondingly, the Fe2+/ascorbate-stimulated lipid peroxidation capacities of microsomal and mitochondrial fractions of skeletal muscle were significantly higher in male mice. 8. The activity of glutathione peroxidase as well as the concentration of lipofuscin were higher in the cardiac muscles of female than male mice.     

摄入异烟肼对家蚕幼虫体内谷胱甘肽氧化还原循环和谷胱甘肽S-转移酶活性的影响

为了建立家蚕Bombyx mori的药物筛选和毒性评价模型, 以剂量为2 000 mg/kg的抗结核模药异烟肼饲喂家蚕5龄第3天幼虫后检测其中肠和脂肪体的抗氧化解毒相关代谢的变化。结果表明： 雌蚕中肠组织中, 总谷胱甘肽(GSH+2GSSG)、 还原型谷胱甘肽(reduced glutathione, GSH)和氧化型谷胱甘肽(oxidized glutathione, GSSG)含量均呈现迅速上升再缓慢下降趋势; 谷胱甘肽S 转移酶(glutathione S-transferase, GST)活性升高到较大值后逐渐降低; GSH/GSSG的比值下降表明, 在72 min后中肠组织向氧化态转移。脂肪体组织中, 总谷胱甘肽、 GSH和GSSG含量变化均呈现迅速下降再迅速上升的趋势; GST活性达到最大值后逐渐降低后趋于平稳; GSH/GSSG比值升高表明, 在72 min后脂肪体组织向还原态转移。无论雌蚕还是雄蚕, 总谷胱甘肽、 GSH和GSSG含量以及GST活性均是脂肪体高于中肠。雌蚕的总谷胱甘肽含量、 GSH和GSSG含量高于雄蚕, 但雄蚕的GST活性高于雌性。结果说明, 摄入异烟肼引起了家蚕幼虫体内谷胱甘肽氧化还原状态的改变和酶活性的变化, 在这个过程中脂肪体起主要解毒代谢作用。     

Influence of estrogen on glutathione levels and glutathione-metabolizing enzymes in uteri and R3230AC mammary tumors of rats

The glutathione content and the activities of several enzymes in its metabolism, glutathione reductase, glutathione peroxidase and γ-glutamyl transpeptidase, were assayed in uteri obtained from estrogen-treated rats and in R3230AC mammary adenocarcinomas obtained from ovariectomized, intact and estrogen-treated hosts. Normal mammary glands, obtained 10–12 days post-partum, were also examined for these parameters.A daily pharmacological dose of 0.4 μg of estradiol-17β induced a maximal increase in uterine weight and in reduced glutathione (GSH); higher doses of estrogen did not significantly increase either of these parameters. Levels of oxidized glutathione (GSSG) were comparable in both estrogen-treated and untreated rats. The time course of the estrogen-induced uterotrophic response was associated with increases in glutathione reductase, glutathione peroxidase and γ-glutamyl transpeptidase activities with the increased GSH level preceding the increase in uterine weight. Compared to neoplasms from intact or ovariectomized animals, tumors from estrogen-treated hosts exhibited significant decreases in levels of GSSG and GSH, as well as in glutathione reductase and glutathione peroxidase activities, but demonstrated a significant elevation of γ-glutamyl transpeptidase activity. Normal glands from lactating rats had decreased GSH levels, lower activities of glutathione reductase and glutathione peroxidase, but elevated γ-glutamyl transpeptidase activity versus tumors from intact rats. Tumors from estrogen-treated rats more closely resembled mammary glands during lactation. The divergent growth responses elicited by estrogen in the uterus and mammary tumor are correlated with the observed changes in GSH levels and enzymes involved in glutathione metabolism.     

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.     

Age-related changes in the activity of antioxidant and redox enzymes in rats

Cellular defense system, including glutathione, glutathione-related enzymes, and antioxidant and redox enzymes, may play crucial roles in the aging of aerobic organisms. To understand the physiological roles of these factors in the aging process, their levels were compared in the livers and brains of 5-week- and 9-month-old rats. GST activity was higher in livers and brains of 9-month-old rats than in those of 5-week-old rats, and brain catalase activity was about 2-fold higher. However, it was unchanged in the livers of the 9-month-old rats. gamma-Glutamylcysteine synthetase activity was about 2-fold higher in the brains of the older rats but again not in their livers. In contrast glutathione synthetase activity appeared to be lower in the livers of the older rats while GSH content did not change with age in livers and brains. Glutathione peroxidase activity was higher in 9-month-old rat brains, but lower in 9-month-old rat livers, while superoxide dismutase activity was higher in both tissues in the older rats. The activities of two redox enzymes, thiol-transferase and thioredoxin reductase, did not change with age, nor did that of glutathione reductase. These results indicate that levels of different cellular defense systems vary with age in an irregular manner.     

Microsomal glutathione-dependent protection against lipid peroxidation acts through a factor other than glutathione peroxidase and glutathione S-transferase in rat liver

Ascorbate-Fe3+-induced and NADPH-induced lipid peroxidation of rat liver microsomes were inhibited by glutathione (GSH). This inhibition was due to microsomal GSH-dependent factor. This factor was heat labile, and storage of microsomes at 4 degrees C for 1 week diminished the activity. GSH could not be substituted by other sulfhydryl compounds tested. Deoxycholate (1 mM) and bromosulfophthalein (0.1 mM) inhibited GSH-dependent protection but did not inhibit microsomal GSH peroxidase activity. Iodoacetate (10 mM) inhibited GSH-dependent protection but did not inhibit microsomal GSH S-transferase. N-Ethylmaleimide (0.1 mM) and oxidized glutathione (10 mM) inhibited GSH-dependent protection but activated microsomal GSH S-transferase activity. These results indicate the existence of a heat-labile, microsomal GSH-dependent protective factor against lipid peroxidation that acts through a factor other than GSH-peroxidase and GSH S-transferase.