PS-B06-1: LOW DOSE SPIRONOLACTONE ALLEVIATES CARDIO-RENAL DISORDER IN EXPERIMENTAL PCOS RAT MODEL BY REDUCTION OF BAX/INFLAMMASOME IMMUNOHISTOCHEMICAL EXPRESSION

Abstract

Objectives: Polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic disorders among women of reproductive age. It has been associated with cardio-renal disturbance. In fact, cardiovascular disease and chronic kidney disease remain the major cause of disease burden worldwide. Mineralocorticoid receptor activation has been demonstrated in various pathological conditions, including cardiovascular and renal dysfunction. Spironolactone is a mineralocorticoid receptor blocker that regulates metabolic-related functions. However, the impact of spironolactone (LSPL), on PCOS associated cardio-renal disorder is unknown. Therefore, the present study hypothesized that LSPL would ameliorate cardio-renal disorders in experimental PCOS animal. Materials and Methods: Female Wistar rats that were eight-week-old were allotted into three groups. The control group received vehicle (distilled water; p.o.), LET-treated group designated as PCOS group received letrozole (1 mg/kg; p.o.), while PCOS+LSPL received a combination of letrozole and LSPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterrupted. Results: The experimental PCOS rats were characterized with insulin resistance as well as, elevated testosterone and LH/FSH with a significant increase in cardiac and renal lipid profile, oxidative stress, inflammatory biomarkers (NF-kappaB and TNF-alpha), LDH and lactate content, and decrease in cardiac and renal antioxidant system (GPX and GSH) compared with the control rats. There was also a significant increase in cardiac GGT but not renal GGT activity in PCOS animals. In addition, immunohistochemical assessment of cardiac and renal tissue showed severe expression of inflammasome and moderate expression of BAX in animals with PCOS. Nevertheless, these perturbations were attenuated following the administration of LSPL. Conclusion: Collectively, the present results suggests that low dose spironolactone attenuates PCOS-associated cardio-renal disorders by reduction of oxidative stress and BAX/Inflammasome expression.