Resveratrol attenuates hyperglycemia-mediated oxidative stress,proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin–nicotinamide-induced experimental diabetic rats

The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin–nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-α, IL-1β, IL-6, NF-κB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5 mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.     

Impact of d-pinitol on the attenuation of proinflammatory cytokines,hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats

Oxidative stress plays a crucial role in the progression and development of diabetes and its complications due to chronic hyperglycemia. The present study was aimed to investigate the kidney tissue protective nature of d-pinitol, a cyclitol present in soybean, by assessing the key markers of hyperglycemia-mediated oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of d-pinitol (50 mg/kg body weight/day) for 30 days to diabetic group of rats showed a significant elevation in the level of total protein and significant decline in the levels of blood urea, serum uric acid, creatinine and advanced glycation endproducts (AGEs) and kidney proinflammatory cytokines such as TNF-α, IL-1β, IL-6, NF-κB p65 subunit and nitrite. Further, d-pinitol administration elicited a significant attenuation in the activities of kidney enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and the levels of kidney non-enzymatic antioxidants such as vitamin E, vitamin C and reduced glutathione (GSH) in the diabetic group of rats, with a concomitant decline in the levels of kidney lipid peroxides, hydroperoxides and protein carbonyls. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of d-pinitol. Thus the present study demonstrated the renoprotective nature of d-pinitol by attenuating the hyperglycemia-mediated proinflammatory cytokines and antioxidant competence in kidney tissues of streptozotocin-induced diabetic rats.     

Influence of treatment of diabetic rats with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague-Dawley rats, normal and streptozotocin-induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, beta-carotene, pycnogenol + beta-carotene, or pycnogenol + beta-carotene + alpha-lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with beta-carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) beta-carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects.     

Effects of beta-carotene on oxidative stress in normal and diabetic rats

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.     

Antioxidant capacity responsible for a hypocholesterolemia is independent of dietary cholesterol in adult rats fed rice protein

Dietary cholesterol and aging are major risk factors to accelerate oxidation process for developing hypercholesterolemia. The major aim of this study is to elucidate the effects of rice protein on cholesterol level and oxidative stress in adult rats fed with and without cholesterol. After 2 weeks of feeding, hepatic and plasma contents of cholesterol, reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and protein carbonyl (PCO) were measured. In liver, total antioxidative capacity (T-AOC), activities of antioxidant enzymes (total superoxide dismutase, T-SOD; catalase, CAT), glutathione metabolizing enzyme activities and gene expression levels (γ-glutamylcysteine synthetase, γ-GCS; glutathione reductase, GR; glutathione peroxidase, GPx) were determined. Under cholesterol-free/enriched dietary condition, T-AOC, activities of T-SOD and CAT, glutathione metabolism related enzymes' activities and mRNA levels (γ-GCS, GR and GPx) were effectively stimulated by rice proteins as compared to caseins. Compared with caseins, rice proteins significantly increased hepatic and plasma GSH contents, whereas hepatic and plasma accumulations of MDA, PCO and GSSG were significantly reduced by rice protein-feedings. As a result, the marked reductions of cholesterol in the plasma and in the liver were observed in adult rats fed rice proteins with and without cholesterol. The present study demonstrates that the hypocholesterolemic effect of rice protein is attributable to inducing antioxidative response and depressing oxidative damage in adult rats fed cholesterol-free/enriched diets. Results suggest that the antioxidant capability involved in the hypocholesterolemic action exerted by rice protein is independent of dietary cholesterol during adult period.     

Characterization of Oxidative Stress in Various Tissues of Diabetic and Galactose-fed Rats

Rats fed a galactose-rich diet have been used for several years as a model for diabetes to study, particularly in the eye, the effects of excess blood hexoses. This study sought to determine the utility of galactosemia as a model for oxidative stress in extraocular tissues by examining biomarkers of oxidative stress in galactose-fed rats and experimentally-induced diabetic rats. Sprague-Dawley rats were divided into four groups: experimental control; streptozotocin-induced diabetic; insulin-treated diabetic; and galactose-fed. The rats were maintained on these regimens for 30 days, at which point the activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase, as well as levels of lipid peroxidation and reduced and oxidized glutathione were determined in heart, liver, and kidney. This study indicates that while there are some similarities between galactosemic and diabetic rats in these measured indices of oxidative stress (hepatic catalase activity levels and hepatic and renal levels of oxidized glutathione in both diabetic and galactosemic rats were significantly decreased when compared to normal), overall the galactosemic rat model is not closely parallel to the diabetic rat model in extra-ocular tissues. In addition, several effects of diabetes (increased hepatic glutathione peroxidase activity, increased superoxide dismutase activity in kidney and heart, decreased renal and increased cardiac catalase activity) were not mimicked in galactosemic rats, and glutathione concentration in both liver and heart was affected in opposite ways in diabetic rats and galactose- fed rats. Insulin treatment reversed/prevented the activity changes in renal and cardiac superoxide dismutase, renal and cardiac catalase, and hepatic glutathione peroxidase as well as the hepatic changes in lipid peroxidation and reduced and oxidized glutathione, and the increase in cardiac glutathione. Thus, prudence should be exercised in the use of experimentally galactosemic rats as a model for diabetes until the correspondence of the models has been more fully characterized.     

Hymenolepis diminuta: Activity of anti-oxidant enzymes in different parts of rat gastrointestinal tract

The aim of this study was to assess the intensity of oxidative stress by measuring levels of lipid peroxidation products in the duodenum, jejunum and colon of rats infected with Hymenolepis diminuta and evaluate the effectiveness of protection against oxidative stress by measuring the glutathione levels and activity of anti-oxidant enzymes: superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase.In exposed rats we observed a significant increase of lipid peroxidation products in the duodenum and jejunum. A significant decrease in superoxide dismutase activity in all the examined parts of the digestive tract was observed. Additionally, rats from 16 to 40 days post H. diminuta infection (dpi) had a decreased catalase activity in the colon, while at 60 dpi it increased. The glutathione peroxidase activity increased significantly in the colon at 60 dpi. The increase in glutathione reductase activity was observed in the colon in rats 60 dpi. There was a lack of changes in the levels of glutathione in the duodenum and a significant increase in its concentration in the jejunum and colon from 40 to 60 dpi and from 16 to 40 dpi, respectively. In this study we observed altered activity of anti-oxidant enzymes and glutathione level in experimental hymenolepidosis, as a consequence of oxidative stress. It may indicate a decrease in the efficiency of intestinal protection against oxidative stress induced by the presence of the parasite. The imbalance between oxidant and anti-oxidant processes may play a major role in pathology associated with hymenolepidosis.     

Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats

Using diabetes mellitus as a model of oxidative damage, this study investigated whether subacute treatment (10 mg/kg/day, intraperitoneally for 14 days) with the compound piperine would protect against diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively) content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Piperine treatment of normal rats enhanced hepatic GSSG concentration by 100% and decreased renal GSH concentration by 35% and renal glutathione reductase activity by 25% when compared to normal controls. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with piperine reversed the diabetic effects on GSSG concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation. Piperine treatment did not reverse the effects of diabetes on hepatic GSH concentrations, lipid peroxidation, or glutathione peroxidase or catalase activities; on renal superoxide dismutase activity; or on cardiac glutathione peroxidase or catalase activities. These data indicate that subacute treatment with piperine for 14 days is only partially effective as an antioxidant therapy in diabetes.     

Influence of treatment of diabetic rats with combinations of pycnogenol, β‐carotene,and α‐lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, β‐carotene, and α‐lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague‐Dawley rats, normal and streptozotocin‐induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, β‐carotene, pycnogenol + β‐carotene, or pycnogenol + β‐carotene + α‐lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with β‐carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) β‐carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:345–352, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20046     

6-Gingerol prevents cisplatin-induced acute renal failure in rats

BACKGROUND: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused by oxygen-centered free radicals may contribute to the pathogenesis of cisplatin-induced acute renal failure. 6-Gingerol is claimed to be a potent antioxidant. The present study was performed to explore the renoprotective potential of 6-gingerol on cisplatin-induced oxidative stress and renal dysfunction. METHODS: 6-Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. RESULTS: A single dose of cisplatin resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. 6-Gingerol treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. CONCLUSIONS: The present study demonstrates the renoprotective potential of 6-gingerol against cisplatin-induced oxidative stress and renal dysfunction in rats. Hence, 6-gingerol has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity.     

Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase

Background

Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN.

Methods

The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats.

Results

The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys.

Conclusions

Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats

Hyperglycemia-induced oxidative stress plays a vital role in the progression of diabetic nephropathy. The renoprotective nature of taurine has also been reported earlier; but little is known about the mechanism of this beneficial action. The present study has, therefore, been carried out to explore in detail the mechanism of the renoprotective effect of taurine under diabetic conditions. Diabetes was induced in rats by alloxan (single i.p. dose of 120?mg/kg body weight) administration. Taurine was administered orally for 3?weeks (1% w/v in drinking water) either from the day on which alloxan was injected or after the onset of diabetes. Alloxan-induced diabetic rats showed a significant increase in plasma glucose, enhanced the levels of renal damage markers, plasma creatinine, urea nitrogen and urinary albumin. Diabetic renal injury was associated with increased kidney weight to body weight ratio and glomerular hypertrophy. Moreover, it increased the productions of reactive oxygen species, enhanced lipid peroxidation and protein carbonylation in association with decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia enhanced the levels of proinflammatory cytokins (TNF-α, IL-6, IL-1β) and Na⁺–K⁺-ATPase activity with a concomitant reduction in NO content and eNOS expression in diabetic kidney. Investigation of the oxidative stress-responsive signaling cascades showed the upregulation of PKCα, PKCβ, PKCε and MAPkinases in the renal tissue of the diabetic animals. However, taurine administration decreased the elevated blood glucose and proinflammatory cytokine levels, reduced renal oxidative stress (via decrease in xanthine oxidase activity, AGEs formation and inhibition of p47phox/CYP2E1 pathways), improved renal function and protected renal tissue from alloxan-induced apoptosis via the regulation of Bcl-2 family and caspase-9/3 proteins. Taurine supplementation in regular diet could, therefore, be beneficial to regulate diabetes-associated renal complications.     

Early oxidative stress in the diabetic kidney: effect of DL-alpha-lipoic acid

Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The attempts to identify early markers of diabetes-induced renal oxidative injury resulted in contradictory findings. We characterized early oxidative stress in renal cortex of diabetic rats, and evaluated whether it can be prevented by the potent antioxidant, DL-alpha-lipoic acid. The experiments were performed on control rats and streptozotocin-diabetic rats treated with/without DL-alpha-lipoic acid (100 mg/kg i.p., for 3 weeks from induction of diabetes). Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats vs. controls (p <.01) and this increase was partially prevented by DL-alpha-lipoic acid. F(2) isoprostane concentrations (measured by GCMS) expressed per either mg protein or arachidonic acid content were not different in control and diabetic rats but were decreased several-fold with DL-alpha-lipoic acid treatment. Both GSH and ascorbate (AA) levels were decreased and GSSG/GSH and dehydroascorbate/AA ratios increased in diabetic rats vs. controls (p <.01 for all comparisons), and these changes were completely or partially (AA) prevented by DL-alpha-lipoic acid. Superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase, and NADH oxidase, but not catalase, were upregulated in diabetic rats vs. controls, and these activities, except glutathione peroxidase, were decreased by DL-alpha-lipoic acid. In conclusion, enhanced oxidative stress is present in rat renal cortex in early diabetes, and is prevented by DL-alpha-lipoic acid.     

Quercetin attenuates lindane induced oxidative stress in wistar rats

A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (γ-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane.     

Cold-stress-induced modulation of antioxidant defence: role of stressed conditions in tissue injury followed by protein oxidation and lipid peroxidation

The aim of this study was to determine the effects of cold stress on antioxidant enzyme activities and examine protein oxidation and lipid peroxidation in various tissues (brain, liver, kidney, heart and stomach). Twenty male Wistar rats (3 months old) weighing 220 ± 20 g were used. The rats were randomly divided into two groups of ten: the control group and the cold stress group. Cold stress was applied to the animals by maintaining them in a cold room (5 °C) for 15 min/day for 15 days. Blood samples were taken for measuring plasma corticosterone levels. Tissues were obtained from each rat for measuring the antioxidant enzyme activities, protein oxidation and lipid peroxidation. Corticosterone levels were increased in the cold stress group. Copper, zinc superoxide dismutase activities were increased in the brains, livers and kidneys, whereas they decreased in the hearts and stomachs of rats in the cold stress group. Catalase activities were increased in the brains, livers, kidneys and hearts, whereas they decreased in the stomachs of rats in the cold stress group. Selenium-dependent glutathione peroxidase activities were increased in the brain, liver, heart and stomach. Reduced glutathione levels were decreased, while levels of protein carbonyl, conjugated diene and thiobarbituric-acid-reactive substances were increased in all tissues of the cold stress group. These results lead us to conclude that cold stress can disrupt the balance in an oxidant/antioxidant system and cause oxidative damage to several tissues by altering the enzymatic and non-enzymatic antioxidant status, protein oxidation and lipid peroxidation.     

Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats

In view of the antioxidant properties of melatonin, the effects of melatonin on the oxidative-antioxidative status of tissues affected by diabetes, e.g. liver, heart and kidneys, were investigated in streptozotocin (STZ)-induced diabetic rats in the present study. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tissues were compared in three groups of 10 rats each (control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)). In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60 mg kg(-1) dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10 mg kg(-1) i.p. dose of melatonin per day. After 6 weeks, the rats in groups II and III had significantly lower body weights and higher blood glucose levels than the rats in group I (p < 0.001 and p < 0.001, respectively). MDA levels in the liver, kidney and heart of group II rats were higher than that of the control group (p < 0.01, p < 0.05, p < 0.01, respectively) and diabetic rats treated with melatonin (p < 0.05). The GSH, GSH-Px and SOD levels increased in diabetic rats. Treatment with melatonin changed them to near control values. Our results confirm that diabetes increases oxidative stress in many organs such as liver, kidney and heart and indicate the role of melatonin in combating the oxidative stress via its free radical-scavenging and antioxidant properties.     

Benfotiamine Enhances Antioxidant Defenses and Protects against Cisplatin‐Induced DNA Damage in Nephrotoxic Rats

The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin‐induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8‐hydroxy‐2'‐deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin‐induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:398‐405, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21501     

Ameliorative effect of 20-OH ecdysone on streptozotocin induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was to evaluate the effects of 20-OH ecdysone on hyperglycemia mediated oxidative stress in streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by single intraperitoneal injection of STZ (45 mg/kg b.w.) dissolved in 0.1 mol/L citrate buffer (pH 4.5). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of non-enzymic antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic rats. Moreover, hepatic markers (aspartate aminotransferase and alanine aminotransferase) and renal markers (urea, creatinine) were significantly increased in diabetic rats as compared to control rats. Upon treatment with 20-OH ecdysone to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that 20-OH ecdysone exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its hypoglycemic potential. The effect produced by the 20-OH ecdysone on various parameters was comparable to that of glibenclamide – an antidiabetic drug.     

Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats

Coenzyme Q10 is an endogenous lipid soluble antioxidant. Because oxidant stress may exacerbate some complications of diabetes mellitus, this study investigated the effects of subacute treatment with exogenous coenzyme Q10 (10 mg/kg/day, i.p. for 14 days) on tissue antioxidant defenses in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione contents, and activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited increased oxidative stress and disturbances in antioxidant defense when compared with normal controls. Treatment with the lipophilic compound coenzyme Q10 reversed diabetic effects on hepatic glutathione peroxidase activity, on renal superoxide dismutase activity, on cardiac lipid peroxidation, and on oxidized glutathione concentration in brain. However, treatment with coenzyme Q10 also exacerbated the increase in cardiac catalase activity, which was already elevated by diabetes, further decreased hepatic glutathione reductase activity, augmented the increase in hepatic lipid peroxidation, and further increased glutathione peroxidase activity in the heart and brain of diabetic animals. Subacute dosing with coenzyme Q10 ameliorated some of the diabetes-induced changes in oxidative stress. However, exacerbation of several diabetes-related effects was also observed.