Novel therapeutic insights of Alpha lipoic acid: antioxidant, and steroidogenesis regulatory role in letrozole induced PCOS rat model

Oxidative stress is widely identified as a critical etiological player in several diseases, including PCOS as it is a multifaceted endocrinological disorder affecting females during their reproductive life. Alpha lipoic acid is widely known for its role as a potent antioxidant and energy metabolism regulator. However, its mechanistic pathway in regulating PCOS hasn’t been elucidated yet. For this aim, 24 adult female rats were allocated into 4 groups (n=6). The first group is the control group, the second group is the PCOS group that received letrozole orally (1mg/kg bwt) to induce PCOS, third and fourth groups are PCOS groups that were treated orally with alpha lipoic acid (ALA) (100 mg/kg bwt) and clomiphene citrate (CC) (2mg/kg bwt) respectively. After 35 days, intraovarian redox status was assessed via malondialdehyde (MDA) levels, catalase (CAT) enzymatic activity, and reduced glutathione (GSH) levels measurement. Also, serum metabolic profile and hormonal analysis were determined. Ovarian relative expression of CYP11A1, CYP17A1, and STAR genes involved in the steroidogenesis pathway was evaluated. Furthermore, ovarian histomorphometric analysis besides Caspase 3 (casp3) immune expression of granulosa cells was performed. ALA treatment revealed significant improvement in the intraovarian redox status, metabolic profile, hormonal analysis as well as relative gene expression of the steroidogenesis pathway. In addition, significant improvement in the ovarian histomorphometric analysis. Also, ALA treatment reduced granulosa cells' immune expression of casp 3. So, ALA is considered a promising adjunct therapy for PCOS owing to its antioxidant and steroidogenesis regulatory role.