Protective effects of zinc on oxidative stress enzymes in liver of protein-deficient rats

Persons afflicted with protein malnutrition are generally deficient in a variety of essential micronutrients like zinc, copper, iron, and selenium, which in turn affects number of metabolic processes in the body. To evaluate the protective effects of zinc on the enzymes involved in oxidative stress induced in liver of protein-deficient rats, the current study was designed. Zinc sulfate at a dose level of 227 mg/L zinc in drinking water was administered to female Sprague-Dawley normal control as well as protein-deficient rats for a total duration of 8 weeks. The effects of zinc treatment in conditions of protein deficiency were studied on rat liver antioxidant enzymes, which included catalase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), glutathione reduced (GSH), and glutathione-S-transferase (GST). Protein deficiency in normal rats resulted in a significant increase in hepatic activities of catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase and the levels of lipid peroxidation. A significant inhibition in the levels of reduced glutathione and the enzyme activity of superoxide dismutase has been observed after protein deficiency in normal rats. Interestingly, Zn treatment to protein-deficient animals lowered already raised activity catalase, glutathione peroxidase, and glutathione-S-transferase and levels of lipid peroxidation to significant levels when compared to protein-deficient animals. Also, Zn treatment to the protein-deficient animals resulted in a significant elevation in the levels of GSH and SOD activity as compared to their respective controls, thereby indicating its effectiveness in regulating their levels in adverse conditions. It has also been observed that concentrations of zinc, copper, iron, and selenium were found to be decreased significantly in protein-deficient animals. However, the levels of these elements came back to within normal limits when zinc was administrated to protein-deficient rats. This study concludes that zinc has the potential to regulate the activities of oxidative stress enzymes as well as essential hepatic elements.     

Hepatoprotective Role of Zinc in Lead-Treated,Protein-Deficient Rats

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.     

Hepatoprotective role of zinc in lead-treated, protein-deficient rats

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.     

Effect of alpha-tocopherol on lipid peroxidation in isoproterenol induced myocardial infarction in rats

The effect of alpha-tocopherol pretreatment on lipid peroxidation and antioxidant status in isoproterenol induced myocardial infarction was studied in rats. Isoproterenol administered rats showed a significant increase in lipid peroxides in serum, heart and aorta. A significant increase in serum iron level with a significant decrease in iron binding capacity was also observed. The levels of antioxidants such as ceruloplasmin, glutathione and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase decreased significantly in isoproterenol administered rats when compared to control. The activity of Na+K+ATPase decreased significantly and the activity of Ca2+ATPase increased significantly in heart and aorta of isoproterenol administered rats. alpha-tocopherol pretreated rats maintained the levels of antioxidants, membrane bound enzymes and activities of antioxidant enzymes near normal, on isoproterenol administration, thus establishing its effect as an antioxidant.     

Chemopreventive potential of zinc in experimentally induced colon carcinogenesis

The present study was performed to evaluate the efficacy of zinc treatment on colonic antioxidant defense system and histoarchitecture in 1,2-dimethylhydrazine- (DMH) induced colon carcinogenesis in male Sprague-Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH+zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. Increased tumor incidence, tumor size and number of aberrant crypt foci (ACF) were accompanied by a decrease in lipid peroxidation, glutathione-S-transferase, superoxide dismutase (SOD) and catalase. On the contrary, significantly increased levels of reduced glutathione (GSH) and glutathione reductase (GR) were observed in DMH treated rats. Administration of zinc to DMH treated rats significantly decreased the tumor incidence, tumor size and aberrant crypt foci number with simultaneous enhancement of lipid peroxidation, SOD, catalase and glutathione-S-transferase. Further, the levels of GSH and GR were also decreased following zinc supplementation to DMH treated rats. Well-differentiated signs of dysplasia were evident in colonic tissue sections by DMH administration alone. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of neoplasia. EDXRF studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats induced by DMH.     

Prolonged phenobarbital pretreatment abolishes the early oxidative stress component induced in the liver by acute lindane intoxication

Lindane administration to rats (60 mg/kg b.w.) led to an enhancement in the oxidative stress status of the liver at 4 h after treatment, characterized by increases in hepatic thiobarbituric acid reactants (TBARS) formation and chemiluminescence, reduced glutathione (GSH) depletion, and diminution in the biliary content and release of GSH. These changes were observed in the absence of changes in either microsomal functions (cytochrome P450 content, NADPH-dependent superoxide radical production, and NADPH-cytochrome P450 reductase or NADPH oxidase activities) or in oxidative stress-related enzymatic activities (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione-S-transferases), over control values. Phenobarbital (PB) administration (0.1% in drinking water; 15 days) elicited an enhancement in liver microsomal functions, lipid peroxidation, and GSH content, without changes in oxidative stress-related enzymatic activities, except for the elevation in those of glutathione reductase and glutathione-S-transferase, compared to control rats. Lindane given to PB-pretreated rats did not alter liver microsomal functions, lipid peroxidation, glutathione status, or oxidative stress-related enzymatic activities, as compared to PB-pretreated animals. In addition, lindane induced periportal necrosis with hemorrhagic foci in untreated rats, but not in PB-pretreated animals. It is concluded that the early oxidative stress response of the liver to lindane and hepatic injury are suppressed by PB pretreatment via induction of microsomal enzymes in all zones of the hepatic acinus. reserved.     

Fenvalerate induced hepatic oxidative stress in selenium- and/or iodine-deficient rats

Considering the potential adverse effects of selenium and iodine deficiencies, and frequency of intensive but improper use of insecticides, this study was designed to evaluate the effects of a pyrethroid insecticide, fenvalerate, on the oxidant/antioxidant status of liver using a rat model of iodine and/or selenium deficiency. The study was conducted on eight groups of 3-week old Wistar rats. Iodine and/or selenium deficiency was introduced by feeding the animals with a diet containing <0.005 mg selenium/kg and/or supplying with 1% sodium perchlorate containing drinking water for a period of 7 weeks. Fenvalerate exposure (100 mg/kg/d, i.p., for the last 7 days) in normal rats increased hepatic glutathione peroxidase activity and lipid peroxidation, decreased glutathione content, but did not change the activities of catalase or any of the superoxide dismutase forms; in iodine-deficient animals caused only the elevation of lipid peroxidation; in selenium-deficient animals and in combined iodine/selenium deficiency decreased glutathione peroxidase, increased catalase activities and lipid peroxidation, and decreased all the forms of superoxide dismutase activity only in combined deficiency. These results suggested that fenvalerate is an oxidant stress inducer in rat liver, and its potential effects on pro-oxidant/antioxidant balance may also be important for human populations, particularly with iodine and/or selenium deficiencies.     

Hepatoprotective effect of rhinax on antitubercular drug-induced hepato-toxicity in rats

Rhinax, a polyherbal formulation, exhibited hepatoprotective function when tested against antitubercular drug-induced hepatotoxicity in rats. Suppression of GSH and antioxidant enzymes "superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), gultathionle peroxidase (GPx) and glutathione S-transferase (GST) were noticed in the liver of antitubercular chemotherapeutic agents (namely isoniazid, rifampicin and pyrazinamide) treated animals accompanied with an increase in cytochrome P-450 contents and increased production of lipid peroxidation. Rhinax afforded hepatoprotection by inhibiting lipid peroxidation and, as a result, the animals showed improved antioxidant status.     

Effect of sub-chronic selenium toxicosis on lipid peroxidation,glutathione redox cycle and antioxidant enzymes in calves

The present investigation reports the effect of sodium selenite-induced sub-chronic toxicity in crossbred cow calves on various antioxidant enzymes. Sodium selenite (0.25 mg/kg for 16 w) resulted in characteristic signs of sub-chronic selenosis, ie alopecia, cracking and enlargement of hooves, interdigital lesions, ring formation on the coronet region, and gangrene at tip of the tail. The sodium selenite resulted in significant rise of blood selenium levels and concurrent increase in erythrocytic glutathione peroxidase (GPx) activity. Blood selenium levels and GPx activity had a high positive correlation (r = 0.97). Blood glutathione levels were lowered from 211.1 +/- 13.4 to 95.56 +/- 11.8 microg/ml. Selenosis caused oxidative stress as evidenced by a 3-fold increase in lipid peroxidation: activities of glutathione-S-transferase, glutathione reductase, superoxide dismutase and catalase were significantly increased. These findings support the hypothesis that the pro-oxidant attributes of selenium play important roles in its toxicity.     

Effects of chronic ethanol administration on free radical defence in rat myocardium.

Cellular protection against free radical reactions was measured in myocardium from ethanol-fed rats using ethanol administration in drinking water as a model of moderate alcohol intoxication. The activities of Cu,Zn-superoxide dismutase (SOD) and glutathione-S-transferase were higher in ethanol-fed rats than in controls, whereas Mn-SOD, catalase and glutathione peroxidase activities were not altered by ethanol treatment. Myocardial zinc was higher and selenium concentration lower in ethanol-fed rats than in controls. Ethanol consumption, which failed to modify the myocardial vitamin E level, did not result in increased lipid peroxidation, but decreased cytosolic and membraneous protein thiols.     

Effect of zinc on hepatic lipid peroxidation and antioxidative enzymes in ethanol-fed rats

A 3-ml aliquot of 30% ethanol was fed daily to normal as well as zinc-treated (227 mg l(-1)) rats for periods of 2, 4 and 8 weeks. A highly significant increase in the levels of hepatic lipid peroxidation was observed in ethanol-fed rats after 4 and 8 weeks of treatment. On the other hand, the levels of lipid peroxidation came down significantly following ethanol feeding to zinc-treated rats. The activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) in liver were elevated significantly after ethanol administration to rats for durations of 2, 4 and 8 weeks. Interestingly, zinc treatment to rats given ethanol was able to bring down the elevated levels of SOD, catalase and GPx to within normal limits, However, zinc administration alone did not cause any significant alteration in the activities of these antioxidative enzymes.     

Effect of acute and chronic administration of sodium valproate on lipid peroxidation and antioxidant system in rat liver

Changes in glutathione and lipid peroxide levels as well as in the activities of superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferase have been studied in rats after acute and chronic sodium valproate treatments. Glutathione levels were decreased only after acute sodium valproate treatment. Neither acute nor chronic treatment influenced lipid peroxidation but induced glutathione-S-transferase activity significantly. On the other hand, no alterations in glutathione peroxidase and superoxide dismutase activities were found, except slight induction of catalase activity after acute administration of sodium valproate. These results indicate that sodium valproate treatment did not induce oxidative stress in the liver.     

The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats

The antioxidant effect of pterostilbene on streptozotocin-nicotinamide-induced diabetic rats has been assessed. The activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was significantly decreased in liver and kidney of diabetic animals when compared with normal control. There were significant improvements in these activities after treatment with pterostilbene at a dose of 40 mg kg(-1) for six weeks. The increased levels of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in liver and kidney of diabetic rats were also normalized by treatment with pterostilbene. Chronic treatment of pterostilbene remarkably reduced the pathological changes observed in liver and kidney of diabetic rats. These results indicated the antioxidant property of pterostilbene.     

Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency

The effect on antioxidant defense system of liver and kidney of sub-acute i.p. exposure to sodium arsenite (3.33 mg/kg b.w. per day) for 14 days was studied in male Wistar rats fed on an adequate (18%) or a low (6%) protein diet. Following arsenic treatment, liver showed significantly enhanced concentration of glutathione and increased activities of glutathione reductase and glutathione-S-transferase on either of the dietary protein levels. Liver glutathione peroxidase and glucose-6-phosphate dehydrogenase activities increased significantly on an adequate protein diet while glutathione peroxidase activity decreased significantly on a low-protein diet. Lipid peroxidation and superoxide dismutase activity of liver remained unaltered on either of the dietary protein levels. On the other hand, kidney of arsenic-treated rats receiving either of the dietary protein levels showed significantly increased lipid peroxidation and decreased superoxide dismutase and catalase activities. Kidney glutathione content and glutathione reductase activity remained unaltered while glutathione peroxidase activity increased and glutathione-S-transferase activity decreased significantly on a low-protein diet following exposure to arsenic. On an adequate protein diet glucose-6-phosphate dehydrogenase activity in kidney, however, became significantly elevated following arsenic treatment. In Wistar rats, after 14 days of treatment with 3.33 mg As/kg b.w. i.p. the kidney seemed to be more sensitive to arsenic, and liver appears to be protected more by some of the antioxidant components, such as, glutathione, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. It appears that low-protein diet influences the response of some of the cellular protective components against arsenic insult but does not lead to unique findings.     

Brain Lipid Peroxidation and Antioxidant Status After Acute Methacrylonitrile Intoxication

The status of brain antioxidant enzymes and glutathione in methacrylonitrile (MeAN)-intoxicated Wistar rats was correlated with the levels of lipid peroxidation products. Optimum changes were observed 30 min and 60 min after oral administration of MeAN at dosages of 50 mg/kg body weight per day (0.25 LD₅₀) and 100 mg/kg body weight per day (0.5 LD₅₀). An increase in lipid peroxidation products, decrease in the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), and decrease in reduced glutathione (GSH) were observed. These studies suggest that the membrane lipid peroxidation observed in MeAN intoxication is related, in part, to a compromised antioxidant defense system.     

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of Superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.     

Cardioprotective effects of Sesbania grandiflora in cigarette smoke-exposed rats

Cigarette smoke is a major risk factor of coronary heart disease, myocardial infarction, and cardiac death. It has been reported to contain large amounts of oxidants. This study was undertaken to evaluate the cardioprotective effects of Sesbania grandiflora (S. grandiflora) against cigarette smoke-induced oxidative damage in rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day orally) for a period of 3 weeks. Lactate dehydrogenase activity in serum and cardiac lipid peroxidation product level were significantly increased while the activities of cardiac superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase then the levels of reduced glutathione, vitamin C, and vitamin E were significantly decreased in rats exposed to cigarette smoke. Besides, copper level was elevated, whereas zinc, manganese, and selenium levels were significantly diminished in the heart of rats exposed to cigarette smoke. Treatment with SGAS restored the antioxidant status and retained the levels of micronutrients. These results suggest that chronic cigarette smoke exposure increases the oxidative stress, thereby disquieting the cardiac defense system and S. grandiflora protects the heart from the oxidative damage through its antioxidant potential.     

Effect of Acute and Chronic Administration of Sodium Valproate on Lipid Peroxidation and Antioxidant System in Rat Liver

Abstract Changes in glutathione and lipid peroxide levels as well as in the activities of superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferase have been studied in rats after acute and chronic sodium valproate treatments. Glutathione levels were decreased only after acute sodium valproate treatment. Neither acute nor chronic treatment influenced lipid peroxidation but induced glutathione-S-transferase activity significantly. On the other hand, no alterations in glutathione peroxidase and superoxide dismutase activities were found, except slight induction of catalase activity after acute administration of sodium valproate. These results indicate that sodium valproate treatment did not induce oxidative stress in the liver.     

In vitro effect of methanol on folate-deficient rat hepatocytes

Methanol is primarily metabolized by oxidation to formaldehyde and then to formic acid. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports the in vitro antioxidant effect of vitamin E on isolated hepatocytes of folic acid deficient rats rendered so as to emulate a human hepatocyte model. These hepatocytes were treated with 320 microM of methanol per million cells and incubated for 30 min. The microsomal fraction of these hepatocytes showed a decreased level of superoxide dismutase (SOD), with increase in lipid peroxidation (LPO) shown by increase in recorded levels of malondialdehyde (MDA). Catalase activity was shown to be increased. Levels of reduced glutathione (GSH) were decreased and the activity of glutathione peroxidase (GSH-Px) and of glutathione reductase (GSSG-R) were not altered. The hepatocytes of folate deficient rats pretreated with vitamin E, when subjected to methanol treatment, showed no significant change in SOD levels and a significant decrease in MDA levels. The catalase activity in this group of animals showed a highly significant decrease. These animals had normal levels of GSH, while a significant fall in GSH-Px and GSSG-R levels were observed. These results suggest that Vitamin E exerts a protective effect on hepatocytes by acting as a free radical scavenger, proving its usefulness in treating methanol toxicity.     

Counteraction by glutathione and selenium of the prooxidant effect of alloxan in erythrocytes in vitro

Alloxan produces reactive oxygen species which cause injury to the insulin-producing β-cells of the pancreas. The action of alloxan in the production of free radicals was studied in vitro using rat erythrocytes. Alloxan increased lipid peroxidation (LPO) and decreased the activities of the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in the erythrocytes. Treatment with glutathione (GSH) and/or selenium along with alloxan was able to decrease LPO and increase the activities of the antioxidant enzymes in the erythrocytes. The results suggest that GSH and selenium both counteract the prooxidant effect of alloxan in rat erythrocytes.