Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated with dehydroepiandrosterone

Oxidative stress plays a crucial role in the pathogenesis of chronic diabet ic complications. Normoglycemic and streptozotocin-diabetic rats were treat ed with dehydroepiandrosterone (DHEA) (4 mg/d per rat) for 3 weeks. At the end of treatment, hydroxynonenal, hydroperoxyeicosatetraenoic acids and ant ioxidant levels, as well as Na/K-ATPase activity and membrane fatty acids c omposition were evaluated in kidney homogenates. Chronic hyperglycemia caus ed a marked increase of both hydroxynonenal and lipoxygenase pathway produc ts and a drop in both GSH levels and membrane Na/K-ATPase activity. DHEA tr eatment restored the antioxidant levels to close to the control value and c onsiderably reduced hydroxynonenal and hydroperoxyeicosatetraenoic acid lev els. Moreover, DHEA counteracted the detrimental effect of hyperglycemia on membrane function: the drop of Na/K-ATPase activity in diabetic animals wa s significantly inhibited by DHEA treatment. These results show that DHEA r educes oxidative stress and the consequent increase of lipoxygenase pathway products induced by experimental diabetes in rat kidney; they also suggest that, by reducing the inflammatory response to oxidative stress, DHEA trea tment might delay the progression of diabetic kidney disease. (C) 2001 Else vier Science Inc.