Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion.

Glutathione peroxidase and thioredoxin reductase are selenocysteine-dependent enzymes that protect against oxidative injury. This study examined the effects of dietary selenium on the activity of these two enzymes in rats, and investigated the ability of selenium to modulate myocardial function post ischemia-reperfusion. Male wistar rats were fed diets containing 0, 50, 240 and 1000 microg/kg sodium selenite for 5 weeks. Langendorff perfused hearts isolated from these rats were subjected to 22.5 min global ischemia and 45 min reperfusion, with functional recovery assessed. Liver samples were collected at the time of sacrifice, and heart and liver tissues assayed for thioredoxin reductase and glutathione peroxidase activity. Selenium deficiency reduced the activity of both glutathione peroxidase and thioredoxin reductase systemically. Hearts from selenium deficient animals were more susceptible to ischemia-reperfusion injury when compared to normal controls (38% recovery of rate pressure product (RPP) vs. 47% recovery of RPP). Selenium supplementation increased the endogenous activity of thioredoxin reductase and glutathione peroxidase and resulted in improved recovery of cardiac function post ischemia reperfusion (57% recovery of RPP). Endogenous activity of glutathione peroxidase and thioredoxin reductase is dependent on an adequate supply of the micronutrient selenium. Reduced activity of these antioxidant enzymes is associated with significant reductions in myocardial function post ischemia-reperfusion.     

Suppression of fatty acid synthase by dietary polyunsaturated fatty acids is mediated by fat itself,not by peroxidative mechanism

This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme.     

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.     

Role of Glutathione-Dependent Peroxidase in Regulation of Lipoperoxide Utilization in Malignant Tumors

Glutathione content, the activity of glutathione-dependent enzymes (glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and also SOD (superoxide dismutase) and catalase were studied in human malignant tumors (uterus, breast, and ovaries) and normal tissues. Glutathione level and the activity of glutathione-dependent enzymes were 2-3 times higher in the malignant tumors than in normal tissues. A negative correlation between the level of glutathione and glutathione-dependent enzymes (glutathione peroxidase and glutathione S-transferase) in tumors and the efficacy of postoperative chemotherapy may characterize the degree of tumor resistance to chemotherapy and therefore may have prognostic value. Low SOD and catalase activity and high activity of glutathione-dependent enzymes in tumors suggest that glutathione peroxidase and glutathione S-transferase play a major role in peroxide utilization in malignant tumors.     

Effects of paraquat on anti-oxidant system in rats

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.     

Chemopreventive effect of garlic powder diet in diethylnitrosamine-induced rat hepatocarcinogenesis

This study was conducted to examine the effects of dietary garlic powder at the different levels on preneoplastic foci formation and glutathione (GSH)-dependent detoxifying enzyme activities in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed with garlic powder supplemented diets (0, 0.5, 2.0 or 5.0%) for 11 weeks, and induced hepatocarcinogenesis by diethylnitrosamine (DEN) and two-thirds partial hepatectomy in medium-term bioassay system. The 2.0 and 5.0% garlic powder diets suppressed the formation of placental GSH S-transferase positive (GST-P(+)) foci in number (49.7 and 63.1% of DEN-treated control group, respectively) and area (44.2 and 63.9% of DEN-treated control group, respectively). Total GSH content in 2.0% garlic powder diet group was 1.2 fold higher than that in DEN-treated control group. GSH S-transferase activity of 2.0% garlic powder diet group was lower than that in DEN-treated control group, and GSH peroxidase (GPx) activity was significantly increased by garlic powder diets (83 and 164% of DEN-treated control group, respectively). GSH reductase activity, however, did not show a noticeable difference among groups. Therefore, the suppression of GST-P(+) foci formation by garlic powder diets could be partly affected by the increase of total GSH content and GPx activity.     

The effects of in vitro lipid peroxidation on the activity of rat liver microsomal glutathione S-transferase from rats supplemented or deficient in antioxidants

Glutathione S-transferases are a group of multifunctional isozymes that play a central role in the detoxification of hydrophobic xenobiotics with electrophilic centers (1). In this study we investigated the effects of in vitro lipid peroxidation on the activity of liver microsomal glutathione S-transferases from rats either supplemented or deficient in both vitamin E and selenium. Increased formation of malondialdehyde (MDA), a by-product of lipid peroxidation, was associated with a decreased activity of rat liver microsomal glutathione S-transferase. The inhibition of glutathione S-transferase occurred rapidly in microsomes from rats fed a diet deficient in both vitamin E and selenium (the B diet) but was delayed for 15 minutes in microsomes from rats fed the same diet but supplemented with these micro-nutrients (B+E+Se diet). Lipid peroxidation inhibits microsomal glutathione S-transferase and this inhibition is modulated by dietary antioxidants.     

Anticarcinogenic effect and modification of cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-initiated rat hepatocarcinogenesis

The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)- induced hepatocarcinogenesis and cytochrome P450 (CYP) enzymes in weaning male Sprague-Dawley rats by using the medium-term bioassay system of Ito et al. The rats were fed diets that contained 0, 0.5, 2.0 or 5.0% garlic powder for 8 weeks, beginning the diets with the intraperitoneal (i.p.) injection of DEN. The areas of placental glutathione S-transferase (GST-P) positive foci, an effective marker for DEN-initiated lesions, were significantly decreased in the rats that were fed garlic powder diets; the numbers were significantly decreased only in the 2.0 and 5.0% garlic-powder diets. The p-Nitrophenol hydroxylase (PNPH) activities and protein levels of CYP 2E1 in the hepatic microsomes of the rats that were fed the 2.0 and 5.0% garlic powder diet were much lower than those of the basal-diet groups. Pentoxyresorufin O-dealkylase (PROD) activity and CYP 2B1 protein level were not influenced by the garlic-powder diets and carcinogen treatment. Therefore, the suppression of CYP 2E1 by garlic in the diet might influence the formation of preneoplastic foci during hepatocarcinogenesis in rats that are initiated with DEN.     

The influence of hypomagnesemia on erythrocyte antioxidant enzyme defence system in mice

The effect of magnesium deficiency on antioxidant defence system was studied in RBC of mice suffering from hypomagnesemia. The animals were kept for 8, 15 and 22 days on magnesium-deficient diet with consequent reduction of magnesium level in plasma by 38% at the first 8 days and by 64% after 22 days of experiment. The activities of the most important antioxidant enzymes, catalase, glutathione peroxidase, superoxide dismutase, glutathione reductase, glutahione S-transferase were assayed in hemolysates. The level of reduced glutathione in erythrocytes was measured as well. Apart from catalase, the activities of antioxidant enzymes were decreasing. The activity of superoxide dismutase decreased gradually during the experiment and on the 15th and 22nd day of experiment was significantly (P<0,05) lowered by 30 and 32% respectively. The catalase activity was increased on each point of the experiment with the peak value up to 149% on 15th day, and by 32% on 22nd day. Glutathione peroxidase activity was insignificantly reduced. The reduction of Glutatione reductase and Glutathione S-transferase activities by 24 and 21%, respectively, were observed after 8 days of the experiment with a further downward tendency. The reduced glutathione was significantly depleted after 8 days by 33% and was kept on that level in the course of the study. These findings support previous reports on the hypomagnesemia – induced alteration in endogenous enzyme antioxidant defences and glutathione redox cycle of mice.     

Glutathione peroxidases and glutathione reductase activities during Bufo bufo development

Glutathione peroxidases and glutathione reductase activities are expressed from the early stage of Bufo bufo development. Selenium-dependent and selenium-independent glutathione peroxidase activities fluctuated independently. The activity of selenium-independent was found to be higher than that of selenium-dependent glutathione peroxidase through all stages of development. Glutathione reductase activity, after a slight fall from stage 4 to stage 7, constantly increased up to stage 25.     

Developmental study of rat brain glutathione peroxidase and glutathione reductase

Glutathione peroxidase and glutathione reductase activities were measured in whole rat brains at selected ages from birth to adulthood. On a wet weight basis glutathione peroxidase activity increased 70% during development and glutathione reductase activity increased 160%. On a protein basis glutathione peroxidase declined slightly in activity during the first two weeks of life and then maintained the 14-day activity into adulthood while glutathione reductase showed a 30% increase in activity. While less than the developmental changes in many enzymes involved in aerobic glycolysis or catecholamine metabolism, these increases do suggest a role in CNS metabolism.     

The effect of hypoxia on intermediary metabolism and oxidative status in gilthead sea bream (Sparus aurata) fed on diets supplemented with methionine and white tea

The present study evaluates the influence of previous nutritional status, fish fed on diets supplemented with tea and methionine, on acute hypoxia tolerance and subsequent recovery of Sparus aurata juveniles. Four isonitrogenous (45% of protein) and isolipidic (18% lipid) diets were formulated to contain 0.3% methionine, 2.9% white tea dry leaves or 2.9% of white tea dry leaves+0.3% methionine. An unsupplemented diet was used as control. Hepatic key enzymes of intermediary metabolism and antioxidant status, superoxide dismutase isoenzyme profile, glutathione (total, reduced and oxidized) and oxidative damage markers were determined under normoxia, hypoxia challenge and during normoxia recovery. Dietary white tea inclusion decreased plasma glucose levels under normoxia and seemed to induce an increase in anaerobic pathways as showed by enhanced liver lactate dehydrogenase activity. Hypoxia challenge reversed some of the responses induced by diet tea supplementation. Hypoxia decreased plasma glucose levels, increased glucose 6-P-dehydrogeanse activity, decreased superoxide dismutase activity (especially Mn-SOD and CuZn-SOD isoforms) and increased glutathione peroxidase activity in all dietary treatments. Catalase activity during hypoxia varied with dietary treatments and glutathione reductase was not modified. Antioxidant defenses were insufficient to avoid an oxidative stress condition under hypoxia, independently of dietary treatment. In general, pre-challenge values were recovered for almost all parameters within 6 h recovery time.     

Enzymatic antioxidant response of a labrid fish (Coris julis) liver to environmental caulerpenyne

Exposure of marine animals to certain toxic compounds can enhance reactive oxygen species production with subsequent damage to macromolecules and alterations in oxidant defenses levels. Caulerpenyne is the major metabolite synthesized by Caulerpa species, used as chemical defense affecting several cellular and molecular targets. We assessed the changes produced by the presence of Caulerpa spp. in the activities of antioxidant enzymes as well as lipid peroxidation levels in liver of the teleost Coris julis. Fish were captured at two stations with Caulerpa species-Caulerpa taxifolia and Caulerpa prolifera-and at a region with the seagrass Posidonia oceanica as negative control. Caulerpenyne concentration was significantly higher in C. prolifera than in C. taxifolia (p<0.05). Glutathione S-transferase, glutathione peroxidase and glutathione reductase activities were significantly higher in both Caulerpa stations compared to the P. oceanica (p<0.05). No statistical difference (p>0.05) existed in catalase activity between groups. Glutathione reductase activity is significantly higher in C. prolifera station than in C. taxifolia (p<0.05). Despite the variations in the antioxidant enzyme activities, there was no significant difference in malondialdehyde concentration. In conclusion, the production of caulerpenyne by Caulerpa species could induce an antioxidant adaptation in the liver of C. julis in order to prevent oxidative damage.     

Liver and muscle proteolytic activity in male growing rats fed a field bean (Vicia faba L.) diet

Total liver cathepsin A and D and gastrocnemius acid proteolytic activities have been evaluated in male growing rats fed ad libitum over periods of 15 and 30 days on 20%-protein diets containing either casein or raw field bean (Vicia faba L.) as protein sources. It has been found that, compared to the control casein-fed rats, those fed the legume diet exhibited a marked reduction (p less than 0.05) in the rate of growth and protein efficiency rate; liver proteolytic activity increased with ageing in the two dietary treatments and was found to be significantly higher (p less than 0.05) in the legume-fed rats. However, muscle proteolytic activity decreased with ageing and proved significantly increased (p less than 0.05) in the legume-fed rats.     

Effect of glutathione on choleragenic diarrhea and disorders of the antioxidant system of rat intestinal and liver cells

The effects of reduced glutathione on the development of choleragenic diarrhea and the activity of glutathione transferase (GT), glutathione peroxidase (GP-GTB and GP-H2O2), superoxide dismutase (SOD), glutathione reductase (GR) in the small intestine and liver of rats with experimentally ligated jejunal loop have been studied. Diarrhea syndrome was found to decrease markedly after glutathione administration in a dose of 1 g/kg bw. GR activity in the jejunum and liver of rats treated with toxin and the following glutathione administration rose by 210 and 186%, respectively, and then reached the control level. Glutathione transferase activity in the jejunum increased by 150% (P less than 0.05), remaining, however, lower than the control values. The activity of other enzymes tested was unchanged. Polyfunctional cellular activity of glutathione suggests that antidiarrhea effect should be considered as an element of pathogenetic therapy.     

Interaction Between Dietary Carbohydrate and Copper Nutriture on Lipid Peroxidation in Rat Tissues

The effects of the interactions between dietary carbohydrates and copper deficiency on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and their roles in peroxidative pathways were investigated. Weanling rats were fed diets deficient in copper and containing either 62% starch, fructose, or glucose. Decreased activity of SOD was noted in all rats fed the copper-deficient diets regardless of the nature of dietary carbohydrate. However, the decreased activity was more pronouced in rats fed fructose. Feeding the fructose diets decreased the activity of GSH-Px by 25 and 50% in the copper-supplemented and copper-deficient rats, respectively, compared to enzyme activities in rats fed similar diets containing either starch or glucose. The decreased SOD and GSH-Px activities in rats fed the fructose diet deficient in copper were associated with increased tissue per-oxidation and decreased hepatic adenosine triphosphate (ATP). When the fructose in the diet of copper-deficient rats was replaced with either starch or glucose, tissue SOD and GSH-Px activities were increased and these increases in enzyme activity were associated with a tendency toward reduced mitochondrial peroxidation when compared to the corre-sponding values for rats fed fructose throughout the experiment Dietary fructose aggrevated the symptoms associated with copper deficiency, but starch or glucose ameliorated them. The protective effects were more pronounced with starch than with glucose.     

Copper deficient rat heart can compensate for doxorubicin-induced oxidant stress

The hypothesis that copper (Cu) alters drug metabolizing enzymes and functions as an antioxidant nutrient in doxorubicin cardiotoxicity was tested. Male Sprague-Dawley rats were fed Cu adequate (⁺Cu; 5 mg Cu/kg of diet), marginally Cu deficient (MCu; 1.2 mg Cu/kg of diet), or severely Cu deficient (⁻Cu; 0.5 mg Cu/kg of diet) diets for 6 wk. Doxorubicin (1, 2, or 4 mg/kg body wt) or saline were administered intraperitoneally 1 time/wk for 4 wk. Compared to control hearts, Cu, Zn superoxide dismutase activity was decreased by 9% in MCu rats and by 21–40% in⁻Cu rats. Glutathione peroxidase activity was elevated 5–15% in⁻Cu rats. Doxorubicin administration increased heart Cu, Zn superoxide dismutase activity in⁺Cu and⁻Cu rats 18 h after the last of 4 injections, but not 18 h after 1 injection. There was no synergism between doxorubicin and Cu deficiency on lipid peroxidation, plasma creatine phosphokinase, cardiac hypertrophy, electrocardiographic abnormalities, or morphological changes. Heart glutathione S-transferase activity was decreased by Cu deficiency, and like Cu, Zn superoxide dismutase activity, returned to normal in⁻Cu rats given doxorubicin. Thus, the Cu deficient rat heart may be able to compensate for doxorubicin-induced oxidant stress by increasing the activity of Cu,Zn superoxide dismutase and glutathione S-transferase.     

Phenobarbital increases rat hepatic prostaglandin F2 alpha, glutathione S-transferase activity and oxidative stress

Eight-week-old female F344/N rats were fed 3.0 or 6.0% of calories (kcal%) as linoleate with or without 0.05% phenobarbital (PB) for 35 days. PB treatment increased glutathione S-transferase (GST) activity by 80% and prostaglandin (PG) F2 alpha levels 4-fold (p less than 0.05). PB decreased hepatic alpha-tocopherol significantly. Hepatic linoleate was decreased by PB in rats fed 6 kcal% but not 3 kcal% linoleate. Increased dietary linoleate had no significant effect on hepatic PGF2 alpha or alpha-tocopherol levels or GST activity. This study suggests that PB hepatotoxicity and tumor-promoting ability may be mediated, at least in part, by PGF2 alpha. PB's effect on PGF2 alpha could be a result of both GST-mediated prostaglandin synthesis and oxidative stress. The removal of significant amounts of hepatic alpha-tocopherol during oxidative stress induced by PB might diminish endogenous inhibition of hepatic PG synthesis by a-tocopherol.     

Changes in erythrocyte glutathione peroxidase and glutathione reductase in alloxan diabetes

Glutathione peroxidase and glutathione reductase activities were measured in erythrocytes from control, diabetic and insulin-treated diabetic rats. A significant decrease in the activity of glutathione peroxidase and an increase in the glutathione reductase activity were found with increase in the time of diabetes which may result in the alteration in the activity of the pentose phosphate pathway by the modulation of the levels of NADPH. Insulin administration reverses the change in the activity of glutathione peroxidase but does not reverse the glutathione reductase activity during diabetes. The overall changes may be due to changes in the levels of insulin, triiodothyronine and thyroxine.