Evolution of oxidative stress parameters and response to oral vitamins E and C in streptozotocin-induced diabetic rats

Abstract

Type I diabetes in humans and streptozotocin (STZ)-induced diabetes in rats has been associated with oxidative stress, but antioxidant therapy has given contradictory results, in part related to the absence of common conditions used to evaluate in-vivo antioxidant properties. This prompted the study of an experimental model of antioxidant therapy in STZ-treated rats. Adult female rats received STZ (50 mgkg −1 ) and were studied 7 or 14 days later. Adipose tissue weight progressively decreased with the time of treatment, whereas plasma triglycerides increased at 7 days, before returning to control values at 14 days after STZ treatment. STZ diabetic rats had increased plasma thiobarbituric acid reacting substances and a-tocopherol levels, but the latter variable was decreased when corrected for total lipids. STZ diabetic rats showed a higher GSSG/GSH ratio at Day 14 and lower GSH + GSSG at Day 7 in liver. To evaluate the effect of short-term antioxidant therapy, rats received 5 doses of vitamins C and E over 3 days before being killed on Day 14. Treatment with antioxidants decreased plasma lactic acid and thiobarbituric acid reacting substances, as well as urine 8-isoprostane, and decreased plasma uric acid in controls. Vitamins increased the plasma a-tocopherol/lipids ratio only in control rats, although the plasma and liver a-tocopherol concentration increased in both groups. STZ diabetic rats showed moderate oxidative stress and treatment with antioxidant vitamins caused a significant change in a selected group of oxidative stress markers, which reflected an improvement in some of the complications associated with this disease. The present experimental conditions can be used as a sensitive experimental model to study the responsiveness of diabetes to other antioxidant interventions.

Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes

“…However, it was reported previously that in primary cultures of rat hippocampal neurons, VC accumulation inhibited the glucose transport inside the cytoplasm independently of this competition (Patel et al 2001). The lactate production inhibition by VC is in agreement with a study that described a lactic acid plasma concentration decrease in rats with streptozotocin-induced diabetes by a VC/E treatment (Ruperez et al 2008). On the other hand, no statistical effects of VC were observed on the percentage of glucose carbon released as lactate, suggesting that VC did not participate in the aerobic/ anaerobic metabolism of rat adipocytes over a 72-h culture treatment.…”

Fat intake leads to differential response of rat adipocytes to glucose, insulin and ascorbic acid

“…Indeed, it is known that the dehydroascorbic acid (the oxidized form of VC that is transported inside cells) could compete with glucose for GLUT-1 and GLUT-4 transporters 35,36 . The drastic inhibition in lactate production by this vitamin, which was observed in adipocytes from both types, is in accordance with a study describing a lactic acid plasma concentration reduction of dietary feeds by a vitamin C/E treatment in diabetic rats 37 , and again, with a previous report that was performed in adipocytes from lean animals 19 . The present work suggests that the effect of this vitamin is independent of the dietary origin of the cells.…”

Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin

“…Moreover, glycogenolysis (mobilization of glycogen) and lypolysis (triacylglycerol hydrolysis in the adipose tissue) might also contribute to the reduction in weight gain by diabetic rats (Sekar et al 2005). Adipose tissue weight and hepatic glycogen content decreased in the experimental STZinduced diabetes in rats (Ruperez et al 2008). The body weight was restored in the presence of vitamin E in STZ-induced diabetic rats, demonstrating its antidiabetogenic effect.The capacity of vitamin E to protect against the body weight loss could be attributed to its ability to reduce hyperglycaemia.…”