#5878 protective effects of vitamin d on hyperandrogenemia-induced-acute kidney injury through the interaction with the ras/inos pathway

Abstract Background and Aims The onset and development of metabolic abnormalities are closely related to polycystic ovary syndrome (PCOS). It has not yet been determined whether PCOS contributes to kidney injury, and the mechanism underlying the condition is not fully understood. Treatment with vitamin D has been shown to have beneficial effects on women with PCOS and renal disease. This study investigated the hypothesis that vitamin D supplementation exerts renoprotective effects via regulating the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS) pathway Method Female Sprague-Dawley rats were randomly divided into five groups (n = 10): (a) control, (b) sham, (c) dehydroepiandrosterone (DHEA, 6 mg/100 g day-1 S.Q.), (d) DHEA + vitamin D (1000 IU/Kg; 3 days/week), and (e) vitamin D. Plasma, ovary, and kidney levels of angiotensin-converting enzyme (ACE) activity was determined using FAPGG-based colorimetric method. The amount of NO was measured by determining the concentrations of nitrite and nitrate end products in the plasma and tissue samples using the Griess method. Histopathological changes in the ovary and kidney were also evaluated. Results Plasma testosterone increased in DHEA-treated rats compared with controls, indicating a hyperandrogenic state. Further, hyperandrogenemia-induced-acute kidney injury increased the plasma, renal, and ovarian angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite and nitrate levels; these changes were reversed by vitamin D treatment. Conclusion Hyperandrogenemia causes systemic abnormalities through RAS imbalance and NO metabolism disturbances, followed by apparent destruction of renal and ovarian tissues. Vitamin D supplementation attenuated these hyperandrogenemia-associated acute kidney injuries, likely via interaction with the RAS/iNOS pathway.