SODIUM ACETATE AND EPLERENONE RESTORE RENAL GLUTATHIONE AND ADENOSINE CONTENT OF RATS EXPOSED TO TESTOSTERONE DURING LATE GESTATION

Abstract

Objective: The kidney plays a critical role in human health and any alteration to its normal function can lead to severe morbidity and mortality. Prenatal exposure to elevated testosterone level has been linked to several disorders particularly kidney disorders by acting undoubtedly through androgen receptor (AR) whereas the involvement of mineralocorticoid receptor (MR) is unclear. The renal effect of sodium acetate (SAc) during late gestational testosterone exposure is not well known. We therefore hypothesized that SAc or MR blockade would protect the kidney of testosterone-exposed pregnant rats against glutathione and adenosine depletion. Design and method: Twenty-five pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SAc (200 mg/kg; p.o), androgen receptor (AR) blocker, flutamide (Flu; 7.5 mg/kg; p.o) or (MR) blocker, eplerenone (Eple; 0.5 mg/kg) between gestational days 14 and 19. Results: The results showed that in the kidney of rats exposed to gestational testosterone, there were decreased kidney glutathione and adenosine, increased uric acid (UA), xanthine oxidase (XO), malondialdehyde (MDA), lactate dehydrogenase, free fatty acids and decreased nitric oxide (NO). There was also elevated plasma urea and creatinine. However, SAc and Eple comparably reversed all these testosterone-induced effects on the kidney. Conclusions: The findings in the present study demonstrate that testosterone exposure during late gestation caused defective renal antioxidant defense that is mediated by AR and MR. The study also provides evidence that sodium acetate protects the kidneys of gestational testosterone-exposed rats against defective antioxidant defense in like manner as MR or AR antagonist.