Effect of phenobarbital and 3-methylcholanthrene on the early oxidative stress component induced by lindane in rat liver.

1. Lindane administered to untreated rats or rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC) increased liver lipid peroxidation, of the same magnitude in all groups. 2. PB pretreatment produced a 50% increase in lipid peroxidation (TBAR) by liver homogenates and microsomes, an effect accompanied by increases in cytochrome P-450, NADPH-cytochrome P-450 reductase, NADPH oxidase and microsomal superoxide anion production, MC pretreatment resulted in increases in liver cytochrome P-450 and NADPH oxidase only. 3. Pretreatment of rats with PB, but not MC or lindane, gave increases in glutathione peroxidase and reductase. 4. Pretreatment with PB, but not MC, increased liver GSH. Lindane decreased liver GSH to the same extent as PB plus lindane. 5. Biliary GSH, GSSG and bile flow were decreased by lindane to similar extents in all groups. 6. Lindane induced periportal necrosis with haemorrhagic foci in all groups. 7. Data presented indicate that the early lipid peroxidative response of liver to lindane was unchanged by PB- or MC-stimulated hepatic microsomal enzyme induction.     

Effect of phenobarbital and 3-methylcholanthrene on the early oxidative stress component induced by lindane in rat liver

1. Lindane administered to untreated rats or rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC) increased liver lipid peroxidation, of the same magnitude in all groups.

2. PB pretreatment produced a 50% increase in lipid peroxidation (TBAR) by liver homogenates and microsomes, an effect accompanied by increases in cytochrome P-450, NADPH-cytochrome P-450 reductase, NADPH oxidase and microsomal superoxide anion production, MC pretreatment resulted in increases in liver cytochrome P-450 and NADPH oxidase only.

3. Pretreatment of rats with PB, but not MC or lindane, gave increases in glutathione peroxidase and reductase.

4. Pretreatment with PB, but not MC, increased liver GSH. Lindane decreased liver GSH to the same extent as PB plus lindane.

5. Biliary GSH, GSSG and bile flow were decreased by lindane to similar extents in all groups.

6. Lindane induced periportal necrosis with haemorrhagic foci in all groups.

7. Data presented indicate that the early lipid peroxidative response of liver to lindane was unchanged by PB- or MC-stimulated hepatic microsomal enzyme induction.     

Dose-dependent study of the effects of acute lindane administration on rat liver superoxide anion production, antioxidant enzyme activities and lipid peroxidation

The administration of single i.p. doses of lindane (20, 40, 60 and 80 mg/kg) to rats produced a progressive increase in the liver microsomal content of cytochrome P-450 and in the rate of superoxide anion generation, as measured by adrenochrome formation. A dose-dependent increase in lipid peroxidation of liver homogenates, assessed by measuring thiobarbituric acid reactants, was also found. Lindane treatment did not alter the activity of liver glucose-6-phosphate dehydrogenase, glutathione reductase or glutathione peroxidase, while that of superoxide dismutase and catalase was significantly reduced. These changes were accompanied by a progressive liver steatosis. The collected metabolic data were interpreted in terms of a causal relationship between an increase in superoxide radical generation, secondary to cytochrome P-450 induction and a resulting increase in lipid peroxidation. The decrease in superoxide dismutase and catalase activities is likely to contribute to the increased levels of lipid peroxidation in view of their antioxidant properties.     

Induction of oxidative stress by lindane in epididymis of adult male rats

Lindane, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male rats. The mechanism of action of lindane on male reproductive system remains unclear. In the present study we have sought to investigate the effect of lindane on antioxidant parameters and sialic acid levels of caput, corpus and cauda epididymis of adult male rats. Lindane (1, 5, and 50mg/kg per day) was administered orally to adult male rats for 45 days. The animals were killed using anaesthic ether on the day following the last treatment. The body weight of the animals did not show significant change. However, the weights of caput, corpus and cauda epididymis decreased in lindane treated animals. Administration of lindane caused decrease in epididymal sperm count and motility. Sialic acid levels in the epididymis decreased significantly at 5 and 50mg/kg dosage of lindane treatment. Significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase along with increase in hydrogen peroxide generation and lipid peroxidation were observed in lindane treated animals. In conclusion, lindane induces oxidative stress by decreasing the activities of antioxidant enzymes and sialic acid levels in the epididymis thereby causing impaired sperm function.     

Lindane-Induced Oxidative Stress. I. Time Course of Changes in Hepatic Microsomal Parameters,Antioxidant Enzymes,Lipid Peroxidative Indices and Morphological Characteristics

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O^?₂) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment.

2. Hepatic superoxide dismutase (SOD) and catalase decreased 6h after lindane treatment and SOD/O^?₂ ratio progressively decreased during 4 to 24 h after lindane treatment.

3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time.

4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4–6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.     

Hepatoprotective Effect of Curcumin on Lindane-induced Oxidative Stress in Male Wistar Rats

Lindane, an organochlorine pesticide, is recognized as a major public health concern because of its potential toxic effects on human health. Its persistence in the body fluids may lead to continuous blood circulation, liver exposure and hepatotoxicity. The present study was undertaken to evaluate the possible protective role of curcumin on lindane-induced hepatotoxicity. Forty-two healthy adult male Wistar rats were divided into seven groups of six rats each. Group I was given dimethylsulfoxide. A single dose of lindane (60 mg/kg bw) was given to group II. Lindane (30 mg/kg bw) was given daily to group III for 14 days. Treatment with curcumin (100 and 200 mg/kg) was given to groups IV and V before (pretreatment) and to groups VI and VII after (post-treatment) 14 days exposure of lindane. Oxidative stress parameters and antioxidative enzymes were investigated in the liver of exposed and treated rats. A significant increase in lipid peroxidation, and decrease in glutathione level, Superoxide dismutase catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and NADPH quinine reductase activities was observed in liver of rats exposed to lindane. Curcumin (Pre- and post-treatment) nearly normalized all these parameters. Histological alterations were also observed in the liver tissue after lindane exposure. Treatment with curcumin significantly prevented the lindane-induced histological alterations. In conclusion, curcumin has protective effect over lindane-induced oxidative damage in rat liver.     

Lindane-induced oxidative stress. I. Time course of changes in hepatic microsomal parameters, antioxidant enzymes, lipid peroxidative indices and morphological characteristics

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.     

Effects of glycerol-induced acute renal failure on tissue glutathione and glutathione-dependent enzymes in the rat

The activities of tissue glutathione (reduced and oxidized) and glutathione-dependent enzymes such as glutathione S-transferase (GSH S-transferase), glutathione reductase (GSSG reductase) and glutathione peroxidase (GSH-Px) were determined for control and uremic rats. Acute renal failure (ARF) was produced by glycerol-water injection. Cytosolic and microsomal GSH S-transferase activity in the kidney was decreased by 38% and 15%, respectively. Hepatic microsomal GSH S-transferase was also decreased by 40% in uremic rats. GSH-Px activity was decreased by 51% in the cytosolic fraction and 33% in the microsomal fraction in the kidney, but was not affected in the liver and whole blood. GSSG reductase activity was also decreased by 48% in the cytosolic fraction in the kidney of uremic rats. In whole blood, however, GSSG reductase activity was increased by 12-fold (0.66 +/- 0.12 mumol NADPH oxidized/min/ml blood in the control; 8.03 +/- 3.29 mumol NADPH oxidized/min/ml blood in uremia). Although the total glutathione concentrations were not significantly affected, the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the liver and whole blood of uremic rats. In addition to the decreases in hepatic and renal GSH S-transferase activities, which is important in drug disposition, ARF caused decreases in GSSG reductase and GSH-Px activity, which are essential for the protection against lipid peroxidation.     

Rat hepatic microsomal metabolism of ethylenethiourea. Contributions of the flavin-containing monooxygenase and cytochrome P-450 isozymes

The contributions of the rat hepatic flavin-containing monooxygenase (FMO) and cytochrome P-450 isozymes (P-450) in the ethylenethiourea (ETU) mediated inactivation of P-450 isozymes and covalent binding of the compound to microsomal proteins were investigated. In vitro, ETU was found to inhibit P-450 marker activities in microsomes obtained from untreated (UT) and phenobarbital (PB), beta-naphthoflavone (BNF), and dexamethasone (DEX) pretreated rats. This inhibition was dependent on the presence of NADPH and was completely abolished by coincubation with glutathione (GSH). Heat treatment of microsomes prior to ETU-mediated P-450 inactivation led to diminished loss of P-450 marker activities in microsomes obtained from UT and PB-pretreated, but not BNF- or DEX-pretreated rats, suggesting FMO involvement in the inactivation of some P-450 isozymes. Covalent binding of [14C]ETU to microsomal proteins was found to be NADPH-dependent and enhanced with BNF or DEX pretreatment of rats. This binding was completely inhibited by coincubation with GSH. Heat treatment of microsomes and P-450 inactivation studies indicated a predominant role of FMO in the observed covalent binding. Addition of the sulfhydryl reagents dithiothreitol (DTT) or GSH after the incubation of microsomes, [14C]ETU, and NADPH resulted in the complete release of bound ETU, suggesting the reduction of disulfide bonds between oxidized ETU and protein sulfhydryls. Microsomal heme content was not decreased following incubation of microsomes with ETU and NADPH, and P-450 appeared to be converted to P-420.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure

Dimethoate, an organophosphate pesticide, is used in controlling the pests of a variety of crops. The study was carried out to understand the role of dimethoate in inducing oxidative stress leading to generation of free radicals and alterations in antioxidant enzymes and scavengers of oxygen free radicals. The effects of subchronic exposure of dimethoate in the production of oxidative stress were evaluated in male Wistar rats in the present study. Dimethoate was administered orally at doses 0.6, 6, and 30 mg/kg for 30 days in these rats. The results indicated an increase in levels of hepatic Cytochrome P450, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase in liver and brain at doses 6 and 30 mg/kg. There were no significant changes in the level of glucose-6-phosphate dehydrogenase activity except in liver at 30 mg/kg. A decrease in glutathione was observed at 30 and 6 mg/kg in both liver and brain. Glutathione-S-transferase increased at 30 and 6 mg/kg in liver and 30 mg/kg in brain. Erythrocyte acetylcholinesterase was inhibited at 30 and 6 mg/kg doses. Dose-dependent histopathological changes were seen in both liver and brain. This study concludes that oxidative stress due to dimethoate may be ascribed to induction of Cytochrome P450, inhibition of AChE and disturbance in activities of GSH and GST enzymes causing lipid peroxidation and histological and electron microscopic changes in liver and brain.     

Phenobarbital-induced cytosolic cytoprotective mechanisms that offset increases in NADPH cytochrome P450 reductase activity in menadione-mediated cytotoxicity

Hepatocytes isolated from phenobarbital (PB)-pretreated and naive male Sprague-Dawley rats were incubated with menadione under one of three oxygen conditions (0, 21, or 95% oxygen) for 3 hr. During this time, samples were drawn and assayed for lactate dehydrogenase release and trypan blue exclusion as indices of cytotoxicity. Neither parameter indicated any significant difference in menadione-induced cytotoxicity between naive and PB-pretreated hepatocytes. Likewise, no difference was observed between hepatocytes incubated in 21% versus 95% O2. Consistent with the oxyradical hypothesis of menadione-induced cytotoxicity, hepatocytes incubated under 0% O2 (95:5; N2:CO2) did not exhibit any menadione cytotoxicity. Hepatic microsomes prepared from PB-pretreated rats exhibited a threefold increase in NADPH cytochrome P450 reductase activity over those of controls. Menadione-stimulated superoxide (O2-) production was twofold higher in PB pretreated versus naive liver microsomes. However, PB pretreatment failed to produce an increase in O2- production in intact hepatocytes or in hepatocytes disrupted by sonication. The failure of PB pretreatment to increase menadione-induced cytotoxicity and superoxide production in either intact or sonicated hepatocytes suggests that a concomitant cytoprotective mechanism is induced as well. The data further indicate that the cytoprotective elements are located in a nonmicrosomal fraction of the cell. In support of this, we observed PB-induced increases in glutathione levels, glutathione reductase, and DT-diaphorase activities. These findings indicate that PB-induced enhancements of the hepatocellular cytoprotective mechanisms collectively compensate for the increased redox cycling mechanism, resulting in a mitigation of the anticipated increased hepatocellular cytotoxicity of menadione.     

苯巴比妥诱导下大鼠肝微粒体药酶活性与膜流动性变化的相关性

本文用ANS和DPH为荧光探剂,研究苯巴比妥(PB)诱导下大鼠肝微粒体膜脂区流动性与膜药酶活性变化的相关性。结果表明,经PB诱导后在增加肝微粒体蛋白质含量,P-450含量及NADPH-细胞色素C还原酶等酶活性的同时,肝微粒体膜流动性明显增大,且膜深层流动性的增大与膜氨基比林N-脱甲基酶、细胞色素C还原酶活性增加有明显的直线正相关。膜胆固醇/碑脂比值明显降低。此结果提示,肝微粒体膜流动性的适当增大与PB增加单胺氧化酶系统活性之间可能存在着某种联系。     

Mechanisms of lindane-induced hepatotoxicity: alterations of respiratory activity and sinusoidal glutathione efflux in the isolated perfused rat liver.

1. Lindane (25-60 mg/kg) at 24 h after dosage induced a dose-dependent increase in oxygen consumption by perfused rat livers, an effect not observed at early times (2-6 h) after administration. About 60% of the increase in liver oxygen uptake is suppressed by the antioxidant, desferrioxamine, indicating enhanced free radical activity induced by the insecticide. 2. The hepatic content of total GSH equivalents (GSH + 2GSSG) decreased 4 h after lindane treatment (60 mg/kg), together with significant diminution in net and fractional rates of sinusoidal GSH efflux, that returned to control values 24 h after treatment. 3. These data indicate that lindane resulted in marked changes in hepatic oxidative capacity and glutathione metabolism, which condition the production of oxidative stress in the liver at different times of intoxication.     

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 227mg/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 thepotential to regulate the activities of oxidative stress enzymes as well as essential hepatic elements.     

硒多糖、亚砷酸钠对大鼠肝微粒体酶和GSH-Px等的影响

研究了硒多糖、亚砷酸钠在体内、外对大鼠肝微粒体酶细胞色素Ｐ－４５０、ｂ５、ＮＡＤ（Ｐ）Ｈ－细胞色素Ｃ还原酶、谷胱甘肽硫转移酶（ＧＳＴ）的影响;并通过测定硒多糖、亚砷酸钠对肝谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）和脂质过氧化（ＬＰＯ）的影响,探讨了硒、砷相互作用的机理。结果表明：连续７天腹腔注射０．２ｍｇ／ｋｇ硒多糖,细胞色素Ｐ－４５０、ｂ５的含量、ＧＳＴ的活性降低（Ｐ＜０．０５）;硒多糖明显诱导ＧＳＨ－Ｐｘ的活性,降低脂质过氧化,拮抗亚砷酸钠对ＬＰＯ的作用。亚砷酸钠显著增强肝细胞脂质过氧化（Ｐ＜０．０５）,对ＧＳＨ－Ｐｘ和肝微粒体酶无明显影响     

Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosylated hemoglobin A(1c) concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.     

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.     

Mechanisms of lindane-induced hepatotoxicity: Alterations of respiratory activity and sinusoidal glutathione efflux in the isolated perfused rat liver

1. Lindane (25-60?mg/kg) at 24?h after dosage induced a dose-dependent increase in oxygen consumption by perfused rat livers, an effect not observed at early times (2-6?h) after administration. About 60% of the increase in liver oxygen uptake is suppressed by the antioxidant, desferrioxamine, indicating enhanced free radical activity induced by the insecticide.

2. The hepatic content of total GSH equivalents (GSH + 2GSSG) decreased 4?h after lindane treatment (60?mg/kg), together with significant diminution in net and fractional rates of sinusoidal GSH efflux, that returned to control values 24?h after treatment.

3. These data indicate that lindane resulted in marked changes in hepatic oxidative capacity and glutathione metabolism, which condition the production of oxidative stress in the liver at different times of intoxication.     

Cisplatin-induced changes in cytochrome P-450, lipid peroxidation and drug-metabolizing enzyme activities in rat kidney cortex

This study investigates the effects of 3 successive cisplatin administrations on rat kidney cytochrome P-450 and drug-metabolizing enzyme activities. Furthermore, because glutathione (GSH) and its related enzymatic system are involved in cellular detoxification processes, we examined the effects of cisplatin on lipid peroxidation, GSH levels, and GSH reductase and peroxidase activities. Cisplatin induced a decrease in cytochrome P-450, GSH, GSH S-transferase, GSH reductase and GSH peroxidase activities, and an increase in N-glucuronyl transferase, lipid peroxidation and oxidized glutathione (GSSG) in kidney cortical microsomes and cytosolic fractions. It is suggested that cisplatin nephrotoxicity could be explained by its affinity for SH-groups of several enzymes and SH-containing compounds. Among these, GSH and its related enzymatic system play a primary role. Moreover, cisplatin increases lipid peroxidation, which might participate in cisplatin nephrotoxicity.     

Protective effect of bezafibrate on streptozotocin-induced oxidative stress and toxicity in rats

The present study was aimed to find out the protective effect of bezafibrate on lipid peroxidation (LPO), activities of both enzymatic and non-enzymatic antioxidants and histopathological examination of pancreas in streptozotocin (STZ)-induced diabetic rats. Experimental diabetes was induced by a single dose of STZ (60mg/kg, i.p.) injection. The oxidative stress was measured by tissue LPO level, reduced glutathione (GSH) content and by enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in liver and pancreas. Biochemical observations were further substantiated with histological examination of pancreas. The increase in blood glucose, LPO level with reduction in GSH content and decreased enzymatic activities were the salient features observed in diabetic control rats. Administration of bezafibrate (30mg/kg day, p.o.) for 15 days caused a significant reduction in blood glucose and LPO level in STZ treated rats (group III) when compared with diabetic control rats (group II). Furthermore, bezafibrate treated diabetic rats (group III) showed significant increase in the activities of both enzymatic and non-enzymatic antioxidants when compared to diabetic control rats (group II). Degenerative changes of pancreatic beta-cells in STZ treated rats were minimized to near normal morphology by administration of bezafibrate as evident by histopathological examination. The results obtained clearly indicate the role of oxidative stress in the induction of diabetes and suggest a protective effect of bezafibrate in this animal model.