Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats.

Abstract

High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers. The aim of this study was to investigate the effect of alpha-lipoic acid (LA) on oxidant-antioxidant balance in rats fed on a high-fructose diet that showed characteristic features of insulin resistance. Male Wistar rats weighing 150-170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high-fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells were assayed. Levels of non-enzymic antioxidants alpha-tocopherol, ascorbic acid and reduced glutathione were determined in plasma. The levels of lipid peroxides, diene conjugates and thiobarbituric acid-reactive substances were significantly higher in fructose-fed rats. Inadequate antioxidant system was observed in high-fructose-fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose-fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices. Increased lipid peroxidation and deficient antioxidant system are observed in high-fructose-fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.