Endocrine Abstracts

Background: Polycystic ovarian syndrome (PCOS) is a multifactorial condition with metabolic-related complication, including chronic renal disorder, which is the leading cause of renal transplant globally. HDAC inhibitors (HDACi) have been suggested to protect renal function against biological assaults. Nonetheless, the current study investigated the restorative role of HDACi, butyrate in experimental PCOS-induced renal disorder.

Materials and methods: Female Wistar rats (8-week-old) were divided into four groups; control, letrozole (LET), butyrate-treated and LET+butyrate-treated groups. To induce PCOS, 1 mg/kg of letrozole was given (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate was administered for 6 weeks.

Results: Rats with PCOS revealed disruption in glucose homeostasis (hyperinsulinemia and impaired glucose tolerance and insulin resistance) and presented with the phenotypes of PCOS (hyperandrogenism, multiple ovarian cysts and elevated LH/FSH ratio). Increased plasma and renal triglycerides and inflammatory (TNF-α/SDF-1/NF-kB) markers was observed with elevated levels of TGFβ-1, renal lipid (MDA) and redox imbalance (GGT, Nrf2, HIF-1α). Interestingly, animals with PCOS reported a significant increase in body weight as well as renal mass. Whereas, heightened levels of renal function markers (urea, creatinine, urea/creatinine ratio and creatinine kinase) indicating renal dysfunction, which subsequently led to renal apoptosis (Caspase-6) with increased HDAC2 levels. Notwithstanding, administration of butyrate averted the alterations.

Conclusion: The present investigation demonstrates that PCOS is characterized with reno-metabolic dysfunction, which is accompanied by an elevated level of HDAC2 with corresponding reduction in anti-oxidant capacity and increased lipid peroxidation. Furthermore, the study in addition suggests that butyrate restores renal function in PCOS by suppressing HDAC2 activity.

Keywords: Butyrate, Caspase-6, HDAC2, Renal, PCOS.