O53 RENOMETABOLIC DISORDER IN EXPERIMENTAL RAT MODEL OF PCOS IS REVERSED VIA INHIBITION OF PYRUVATE DEHYDROGENASE KINASE 4

Abstract

Background and Objective: Chronic Kidney disorders is a global public health problem, including in women with polycystic ovarian syndrome (PCOS), and is characterized by renal fibrosis, nephrotoxicity and glomerulonephritis, which increases the possibility of renal failure and organ transplant. Pyruvate dehydrogenase kinase 4 (PDK4) has been implicated in mitochondria dysfunction, contributing to metabolic dysregulation in different organs, including kidney. Studies have shown the metabolic regulatory impact of probiotics in human and experimental models. Hence, the present study investigated the therapeutic potential of probiotics on renometabolic disorders associated with experimental PCOS model. The study in addition elucidates the probable involvement of PDK4 in PCOS-associated renometabolic disorders. Methods: Eight-week-old nulliparous female Wistar rats were randomly allotted into four groups (n=6). Letrozole (1 mg/kg) was used to induce PCOS for 3 weeks. Thereafter, probiotics (2 x 107 CFU) was administered for 6 weeks, uninterruptedly. Biochemical parameters, histological analysis, immunohistochemistry and gene expression were carried out with appropriate methods. Results Experimental PCOS rats were characterized with elevated circulating testosterone and the presence of multiple ovarian cysts. In addition, rat with PCOS also manifested insulin resistance, increased plasma urea and creatinine levels, increased renal Gamma glutamyltransferase (GGT), MDA, NF-kappa B, TNF-alpha, TGF-beta 1, caspase-6, HDAC2, while a decrease in G6PD, GSH, renal NO and eNOS, when compared with animals in the control rats. These were associated with elevated level of PDK4 in the renal tissue. However, administration of probiotics ameliorates these renal/metabolic abnormalities. Conclusion: Altogether, the results from the present study revealed that probiotics ameliorates renal dysfunction in PCOS via downregulation of PDK4.