Attenuation of plasma dyslipidemia and oxidative damage by dietary caloric restriction in streptozotocin-induced diabetic rats.

Oxidative stress has been proposed as the pathogenic mechanism linking insulin resistance with endothelial dysfunction during diabetes. The present study investigated the attenuation of plasma dyslipidemia and oxidative damage by caloric restriction in experimental diabetes. Forty male Wistar rats were divided into ad libitum and calorie-restricted groups. The calorie-restricted group was subjected to 30% caloric restriction for 63 days before induction of diabetes to 50% of both groups. Caloric restriction significantly (p<0.01) reduced the body weights, reactive oxygen species (ROS), catalase, total cholesterol levels and non-significantly reduced SOD activities in non-diabetic and diabetic rats. Caloric restriction was also found to improve blood glucose levels, glycated hemoglobin, malondialdehyde, triglyceride, oxidized glutathione and reduced glutathione levels and significantly (p<0.05) increased GPx and GR activities in the experimental animals. The non-diabetic rats fed ad libitum had the most significant increases in body weight which could be due to dyslipidemia. These results indicate that dietary caloric restriction attenuates the oxidative damage and dyslipidemia exacerbated during diabetes as evidenced by the significant reduction in their body weights, ROS, total cholesterol levels and the increases in GPx activity and redox status.

Caloric restriction inhibits up-regulation of inflammatory cytokines and TNF-alpha, and activates IL-10 and haptoglobin in the plasma of streptozotocin-induced diabetic rats.

Diabetes mellitus is a significant risk factor for cardiovascular diseases, and low-grade systemic inflammation, mediated by oxidative stress, may play a central role. Caloric restriction (CR) has been reported to be effective in reducing oxidative stress during diabetes and moderating the expression of some markers of inflammation that are up-regulated during aging. Forty male Wistar rats were randomly divided into four groups: nondiabetic feeding ad libitum and under CR, and diabetic feeding ad libitum and under CR. The animals were subjected to 30% CR and ad libitum feeding for 9 weeks before the induction of diabetes by intraperitoneal injection with 35 mg/kg body weight streptozotocin. The inflammatory cytokines [interleukin (IL)-1beta, IL-4 and IL-6] and tumor necrosis factor alpha up-regulated in diabetes were found to be significantly depressed by CR, whereas the antiinflammatory mediators, haptoglobin and IL-10 levels, were increased. These results indicated that CR could prevent diabetic complications through suppression of inflammatory responses.

Dietary caloric restriction improves the redox status at the onset of diabetes in hepatocytes of streptozotocin-induced diabetic rats.

Enhanced production of free radicals and oxidative stress induced by hyperglycemia play a central role in the pathogenesis of diabetes and its complications. This study assessed the attenuation by dietary caloric restriction on the oxidative and lipid peroxidative effects of diabetes in the liver through reduction in body and organ weights and concomitant metabolic changes. Three-month-old male Wistar rats were subjected to ad libitum feeding and 30% caloric restriction for 9 weeks before induction of diabetes by intraperitoneal injection of 35 mg/kg body weight streptozotocin. The animals were sacrificed 2 weeks after streptozotocin treatment depicting the onset of diabetes. Caloric restriction significantly reduced the organ weights (p<0.01), malondialdehyde (p<0.01) and catalase activity (p<0.01), but significantly increased glutathione reductase activity (p<0.01), and GSH/GSSG ratios (p<0.05). Caloric restriction also non-significantly reduced reactive oxygen species, superoxide dismutase and oxidized glutathione but increased glutathione peroxidase activity and reduced glutathione levels in the diabetic rats. Our data indicate a decrease in lipid peroxidation, improvement in the antioxidant defense systems and restoration of the redox status in the liver by caloric restriction. Therefore, this could provide a non-invasive antioxidant therapy early in diabetes to prevent the development of the complications associated with the disease.

Modulation of the flux patterns in carbohydrate metabolism in the livers of streptozoticin-induced diabetic rats by dietary caloric restriction.

Carbohydrate metabolism is impaired in diabetes. The resultant hyperglycemia could cause tremendous changes in the metabolic activities of the liver. We therefore designed this study to investigate the effects of caloric restriction, which has been shown to improve blood glucose homeostasis, on carbohydrate metabolism in the livers of non-diabetic and streptozotocin-induced diabetic rats. Forty male Wistar rats were divided into two groups of caloric restricted (CR) and ad libitum (AL) fed rats. The caloric restricted animals were subjected to 30% caloric restriction. Feeding experiments were conducted for 9 weeks before the induction of diabetes in 50% of the groups. Caloric restriction was found to significantly decrease glycogen (p<0.001), hepatic glucose (p<0.01), phosphofructokinase (p<0.05), glucokinase (p<0.05), aldose reductase (p<0.05), and sorbitol dehydrogenase (p<0.05) and significantly increase hexokinase (p<0.001), glucose-6-phosphate dehydrogenase (p<0.05), and glucose-6-phosphatase activities (p<0.05) in diabetic and non-diabetic rats. From our results, it is suggested that alteration of the metabolic pathways involved in glucose metabolism in the liver could be one of the various ways in which CR attenuates hyperglycemic effects in diabetes.

Ameliorative effects of dietary caloric restriction on oxidative stress and inflammation in the brain of streptozotocin-induced diabetic rats.

BACKGROUND: There is a strong association between oxidative stress and inflammation in the pathologies of diabetes. Recent evidence suggests that these phenomena could impair brain function. We investigated the potential role of dietary caloric restriction in ameliorating the effects of both oxidative stress and inflammation in the brain of streptozotocin-induced type 2 diabetic rats. METHODS: Forty male Wistar rats were subjected to 30% caloric restriction (20 animals) and ad libitum feeding (20 animals) for 9 weeks before the induction of diabetes in 20 animals (10 from each group) by intraperitoneal injection of 35 mg/kg body weight streptozotocin. RESULTS: Caloric restriction was able to significantly (p>0.05) reduce triglyceride, ROS, IL6, TNF-alpha and body weights in diabetic rats. However, no significant differences were obtained in the antioxidant enzyme (SOD, CAT and GPx) activities except in GPx where caloric restriction increased the levels in both non-diabetic and diabetic rats. CONCLUSION: Caloric restriction was found to ameliorate the oxidative and inflammatory effects of diabetes in the brain. Non-diabetic rats feeding ad libitum were found to have increased levels of oxidative stress and inflammatory biomarkers and these could, in part, be due to their increased body weights.

The effects of dietary caloric restriction on antioxidant status and lipid peroxidation in mild and severe streptozotocin-induced diabetic rats.

BACKGROUND: Dietary caloric restriction (CR) without malnutrition is effective in the control of diabetes mellitus by stabilizing glucose homeostasis and enhancing glycemic control. Mild and severe streptozotocin-induced diabetic and non-diabetic rats were subjected to caloric restriction and ad libitum feeding to evaluate their effects on oxidative stress and lipid profile in the plasma of experimental animals. METHODS: Mild and severe diabetes were induced in Male Wistar rats by intraperitoneal injection of 35 and 65 mg/kg streptozotocin respectively. The experimental animals were subjected to 40% caloric restriction and ad libitum feeding for 9 weeks. RESULTS: CR was effective in significantly reducing body weight, blood glucose, HbA IC and TG concentrations (all p < 0.001) in mild diabetic rats and non-significantly improving the plasma HDL-cholesterol concentrations. However, CR did not produce any significant effect on the antioxidant enzyme activities and MDA concentrations in all the groups nor in any of the parameters measured in non-diabetic rats except their overall weight change. There were significant (p < 0.001) decreases in body weight and non-significant fluctuating results in HbA IC and HDL-cholesterol in severe diabetic animals. CONCLUSIONS: These results demonstrate that caloric restriction is most effective in mild than in non-diabetic or severe diabetic animals.

Modification of renal oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with extracts from Gongronema latifolium leaves.

BACKGROUND: Gongronema latifolium is a tropical plant traditionally used in controlling weight gain in lactating women, as well as diabetic and overall health management. In this experiment, the aqueous and ethanolic extracts were tested to evaluate their effect on renal oxidative stress and lipid peroxidation in non-diabetic and streptozotocin-induced diabetic rats. METHODS: Diabetes was induced in male Wistar rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) (65 mg/kg). The rats were divided into non-diabetic (18) and STZ-induced diabetic (18) rats, and both groups subdivided according to their treatments: aqueous extract (100 mg/kg), ethanolic extract (100 mg/kg) and control (saline solution). Aqueous and ethanolic extracts were administered by gavage in 12-h cycles over a 14-day period. RESULTS: The results indicated that the ethanolic extract significantly normalized catalase (CAT) activity (p<0.01), increased glutathione peroxidase (GPx) activity (p<0.05), and reduced reactive oxygen species (ROS) concentrations (p<0.001). It also nonsignificantly normalized superoxide dismutase (SOD) activity, increased GSH/GSSG ratio and reduced malondialdehyde (MDA) concentrations in the diabetic kidney. The aqueous extract had no effect on the superoxide dismutase activity in the diabetic animals and caused a nonsignificant increase in catalase activity. CONCLUSIONS: The ethanolic extract appeared to be more effective in reducing oxidative stress, lipid peroxidation, and increasing the GSH/GSSG ratio, thus confirming the ethnopharmacological use of G. latifolium in ameliorating the oxidative stress found in diabetics and indicating promise of possible use in lessening morbidity in affected individuals.