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Free Radic Biol Med ; 31(8): 935-42, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11595378

RESUMO

Oxidative stress plays a crucial role in the pathogenesis of chronic diabetic complications. Normoglycemic and streptozotocin-diabetic rats were treated with dehydroepiandrosterone (DHEA) (4 mg/d per rat) for 3 weeks. At the end of treatment, hydroxynonenal, hydroperoxyeicosatetraenoic acids and antioxidant levels, as well as Na/K-ATPase activity and membrane fatty acids composition were evaluated in kidney homogenates. Chronic hyperglycemia caused a marked increase of both hydroxynonenal and lipoxygenase pathway products and a drop in both GSH levels and membrane Na/K-ATPase activity. DHEA treatment restored the antioxidant levels to close to the control value and considerably reduced hydroxynonenal and hydroperoxyeicosatetraenoic acid levels. Moreover, DHEA counteracted the detrimental effect of hyperglycemia on membrane function: the drop of Na/K-ATPase activity in diabetic animals was significantly inhibited by DHEA treatment. These results show that DHEA reduces 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 treatment might delay the progression of diabetic kidney disease.


Assuntos
Desidroepiandrosterona/farmacologia , Nefropatias Diabéticas/prevenção & controle , Eicosanoides/metabolismo , Hiperglicemia/metabolismo , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Ácidos Araquidônicos/metabolismo , Desidroepiandrosterona/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Eicosanoides/antagonistas & inibidores , Ácidos Graxos/metabolismo , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Hiperglicemia/induzido quimicamente , Masculino , Lipídeos de Membrana/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Estreptozocina
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