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Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated with dehydroepiandrosterone
M Aragno1, S Parola, E Brignardello
1Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy.
Abstract:
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.
Insights
Dehydroepiandrosterone (DHEA) reduces oxidative stress and kidney damage in diabetic rats. This suggests DHEA may help slow the progression of diabetic kidney disease by mitigating inflammation.
Area of Science:
- Biochemistry
- Endocrinology
- Nephrology
Background:
- Oxidative stress is a key factor in diabetic complications.
- Chronic hyperglycemia damages kidney tissues and impairs membrane function.
Purpose of the Study:
- To investigate the effects of dehydroepiandrosterone (DHEA) on oxidative stress in experimental diabetic nephropathy.
- To evaluate DHEA's impact on kidney antioxidant levels, lipid peroxidation, and Na/K-ATPase activity.
Main Methods:
- Normoglycemic and streptozotocin-diabetic rats were treated with DHEA for 3 weeks.
- Kidney homogenates were analyzed for hydroxynonenal, hydroperoxyeicosatetraenoic acids, GSH, Na/K-ATPase activity, and fatty acid composition.
Main Results:
- Diabetes increased oxidative stress markers (hydroxynonenal, lipoxygenase products) and decreased GSH and Na/K-ATPase activity.
- DHEA treatment normalized antioxidant levels and significantly reduced oxidative stress markers.
- DHEA counteracted the hyperglycemia-induced decline in Na/K-ATPase activity.
Conclusions:
- DHEA effectively reduces oxidative stress and lipoxygenase pathway product increase in diabetic rat kidneys.
- DHEA treatment may delay diabetic kidney disease progression by reducing inflammation associated with oxidative stress.