P112 SUPPRESSION OF PROTEIN KINASE RNA-LIKE ENDOPLASMIC RETICULUM KINASE BY PROBIOTICS CIRCUMVENTS CARDIOVASCULAR RISK PROFILE IN EXPERIMENTALLY-INDUCED PCOS MODEL

Abstract

Background and Objective: The global cause of death attributable to cardiovascular diseases (CVD). including in women of reproductive age is alarming. Individuals with PCOS usually present CVD as a long-term life-threatening effect of PCOS. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) has been implicated in cardiomyopathy. However, its role in PCOS-induced CVD risk has not been established. Studies have shown that probiotics improves metabolic-related disorders. The present study was designed to investigate the role of PERK in CVD risk associated with PCOS in experimental rat model, and the therapeutic benefits of probiotics. Methods: Eight-week-old female Wistar rats were assigned into four groups (n=6). Polycystic ovarian syndrome was induced by uninterrupted administration of letrozole (1 mg/kg) for 21 days, thereafter, probiotics (2 x 107 CFU) was administered for 6 weeks. Gene expression, biochemical parameters and histological evaluations were performed with Western blot, ELISA, and H&E staining techniques Results: The present findings revealed that animals with PCOS were characterized with phenotypic features such as hyperandrogenemia and multiple cysts in the ovaries. In addition, PCOS rats manifested insulin resistance and increase in glucose regulatory protein (GRP78), together with increased levels of circulating corticosterone, cardiac triglyceride, inflammatory mediators (NF- kappaB/TNF-alpha), TGF-beta1, Caspase-6, and HDAC2, while a decrease in HIF-1alpha and NrF2 was observed when compared with control animals. These were accompanied by elevated expression of PERK. However, treatment with probiotics reversed these systemic, endocrine, metabolic and cardiac anomalies. Conclusion: The present study suggests that probiotics attenuates CVD risk profile in experimental PCOS rat model by suppression of PERK/HDAC2-dependent pathway.