Dehydroepiandrosterone protects tissues of streptozotocin-treated rats against oxidative stress

Chronic hyperglycemia in diabetes determines the overproduction of free rad icals, and evidence is increasing that these contribute to the development of diabetic complications. It has recently been reported that dehydroepiand rosterone possesses antioxidant properties; this study evaluates whether, a dministered daily for three weeks per os, it may provide antioxidant protec tion in tissues of rats with streptozotocin-induced diabetes. Lipid peroxid ation was evaluated on liver, brain and kidney homogenates from diabetic an imals, measuring both steady-state concentrations of thiobarbituric acid re active substances and fluorescent chromolipids. Hyperglycemic rats had high er thiobarbituric acid reactive substances formation and fluorescent chromo lipids levels than controls. Dehydroepiandrosterone-treatment (4 mg/day for 3 weeks) protected tissues against lipid peroxidation: liver, kidney and b rain homogenates from dehydroepiandrosterone-treated animals showed a signi ficant decrease of both thiobarbituric acid reactive substances and fluores cent chromolipids formation. The effect of dehydroepiandrosterone on the ce llular antioxidant defenses was also investigated, as impaired antioxidant enzyme activities were considered proof of oxygen-dependent toxicity. Tn ki dney and liver homogenates, dehydroepiandrosterone treatment restored to ne ar-control values the cytosolic level of reduced glutathione, as well as th e enzymatic activities of superoxide-dismutase, glutathione-peroxidase, cat alase. In the brain, only an increase of catalase activity was evident (p < .05), which reverted with dehydroepiandrosterone treatment. The results de monstrate that DHEA treatment clearly reduces oxidative stress products in the tissues of streptozotocin-treated rats. (C) 1999 Elsevier Science Inc.