Involvement of progesterone receptors in ascorbic acid-mediated protection against ischemia-reperfusion-induced acute kidney injury.

BACKGROUND:Ascorbic acid (AA) is an established antioxidant and has been used for treatment of various disorders. Recent reports suggest that administration of AA increases the level of steroids such as progesterone in the body. The present study investigated the protective role of progesterone against ischemia-reperfusion-induced acute kidney injury (AKI) and possible involvement of progesterone receptors in AA-mediated renoprotection in rats. MATERIALS AND METHODS:The male rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The rats were treated with progesterone (5 and 10 mg/kg, intraperitoneally) and AA (500 mg/kg, intraperitoneally for 1, 2, and 5 d) before AKI. In separate groups, mifepristone, the progesterone receptor antagonist was administered to rats before progesterone (10 mg/kg) and AA treatment (5 d). Various parameters including creatinine clearance, serum urea, uric acid, potassium level, fractional excretion of sodium, lactate dehydrogenase, and microproteinuria were used to assess kidney injury. Moreover, renal tissues were subjected to quantification of oxidative stress and evaluation of histopathologic changes. RESULTS:The exogenous administration of progesterone afforded protection against AKI in a dose-dependent manner that was abolished by mifepristone. The administration of AA for 1, 2, and 5 d induced significant increase in serum progesterone levels and afforded protection against AKI. The antioxidant and renoprotective effect of AA was abolished by prior treatment with mifepristone. CONCLUSIONS:It is concluded that exogenous administration of progesterone exerts significant antioxidant and renoprotective effect. Moreover, the progesterone receptors find their explicit involvement in AA-mediated renoprotection against ischemia-reperfusion-induced AKI in rats.

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