Investigating the role of cuproptosis on total oxidant status and PDHB gene expression in rat model of polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by a range of symptoms including hormonal imbalances, irregular menstrual cycles, and insulin resistance. It has been reported previously that PCOS is related to oxidative stress. In women with PCOS, increased levels of oxidative stress markers and decreased total antioxidant status have been observed. Recent researches highlight that copper levels may be altered in women with PCOS. Elevated serum copper has been observed in association with markers of metabolic syndrome, such as oxidative stress and inflammation. Role of cuproptosis in PCOS have been clarified by recent researches. Cuproptosis is a newly discovered type of regulated cell death characterized by reliance on copper levels, primarily interacting with mitochondrial processes. The process of cuproptosis is initiated when copper ions bind to lipoylated proteins in the tricarboxylic acid cycle. This culminates in a state of proteotoxic stress and ultimately results in cell death. This study focuses on investigating the effect of inhibition of cuproptosis on total oxidant status (TOS) and PDHB gene expression in PCOS model of Wistar rats. Methods: Twenty-five Female Wistar rats (approximately ۷–۸ weeks of age and ۱۷۰ grams of weight) were housed at controlled temperature of ۲۵±۲˚C in standard cages with ۵۵±۱۵% humidity and a ۱۲-h dark/light cycle. In this study we used estradiol valerate (EV) to induce PCOS and Tetrathiomolybdate (TTM) to inhibit cuproptosis. All rats were randomly assigned into ۵ following groups (۵ rats in each group); Control (rats did not receive any interventional substance), PCOS control (PCOS-induced by ۰.۴ mg/kg EV), ATTM۵ (PCOS-induced by ۰.۴ mg/kg EV and treated with ۵ mg/kg TTM), ATTM۱۰ (PCOS-induced by ۰.۴ mg/kg EV and treated with ۱۰ mg/kg TTM), ATTM۲۰ (PCOS-induced by ۰.۴ mg/kg EV and treated with ۲۰ mg/kg TTM). In order to induce PCOS.

کلیدواژه ها:

Polycystic ovary syndrome ، oxidative stress ، copper levels ، cuproptosis ، total oxidant status ، PDHB gene expression ، Wistar rats