Oxidative derangement in rat synaptosomes induced by hyperglycaemia: Restorative effect of dehydroepiandrosterone treatment

Central nervous system damage in diabetes is caused by both cerebral athero sclerosis and the detrimental effect of chronic hyperglycaemia on nervous t issue. Hyperglycaemia is the primer of a series of cascade reactions causin g overproduction of free radicals. There is increasing evidence that these reactive molecules contribute to neuronal tissue damage. Dehydroepiandroste rone (DHEA) has been reported to possess antioxidant properties. This study evaluates the oxidative status in the synaptosomal fraction isolated from the brain of streptozotocin-treated rats and the antioxidant effect of DHEA treatment on diabetic rats. Hydroxyl radical generation, hydrogen peroxide content, and the level of the reactive oxygen species was increased (P < 0 .05) in synaptosomes isolated from streptozotocin-treated rats. The derange ment of the oxidative status was confirmed by a low level of reduced glutat hione and alpha-tocopherol. DHEA treatment (4 mg per day for 3 weeks, per o s) protected the synaptosomes against oxidative damage: synaptosomes from d iabetic DHEA-created rats showed a significant decrease in reactive species (P < 0.05) and in the formation of end products of lipid peroxidation, eva luated in terms of fluorescent chromolipid (P < 0.01). Moreover, DHEA treat ment restored the unsaturated fatty acid content of the membrane and the re duced glutathione and alpha-tocopherol levels to normal levels and restored membrane NaK-ATPase activity close to control levels. The results demonstr ate that DHEA supplementation greatly reduces oxidative damage in synaptoso mes isolated from diabetic rats and suggest that this neurosteroid may part icipate in protecting the integrity of synaptic membranes against hyperglyc aemia-induced damage. BIOCHEM PHARMACOL 60;3:389-395, 2000. (C) 2000 Elsevi er Science Inc.