The protective role of α-lipoic acid in hypothyroidism-related ovarian damage

Abstract

This study aimed to investigate the potential protective effects of α-lipoic acid on ovarian tissue damage provoked by propylthiouracil (PTU)-induced hypothyroidism in rats, focusing on oxidative stress, hormonal changes, and Phosphoinositide 3-kinase / Protein kinase B (PI3K/AKT) signaling pathway activity. Twenty-eight female Sprague–Dawley rats (10–12 weeks, 340–360 g) were randomly divided into four groups (n = 7 each): Control, Hp, Hp + α-lipoic acid, and α-lipoic acid. Hypothyroidism was induced by adding 0.05% PTU to drinking water for 8 weeks. α-lipoic acid (100 mg/kg/day) was administered orally. At the end of the experiment, serum and ovarian tissues were collected for biochemical, histological, and immunohistochemical analyses. Serum thyroid hormones, gonadotropins, TAS, TOS, GRP78, PI3K, and AKT1 levels were measured. Ovarian follicle counts, histopathological changes, and immunohistochemical expression of GRP78, PI3K, and AKT1 were evaluated. PTU administration significantly decreased serum T3, T4, TAS, LH, PI3K, and AKT1 levels while increasing TSH, FSH, TOS, and GRP78 levels compared to the control group (p < 0.001). Histological analysis revealed follicular atresia, granulosa cell degeneration, inflammation, and edema in the Hp group. In contrast, α-lipoic acid treatment attenuated oxidative stress, improved folliculogenesis, reduced histopathological damage, and reversed PTU-induced hypothyroidism alterations in PI3K/AKT1 signaling and GRP78 expression (p < 0.05). α-lipoic acid exerts protective effects against PTU-induced hypothyroidism-related ovarian damage through its antioxidative properties and regulation of PI3K/AKT signaling. These findings suggest that α-lipoic acid may serve as a potential therapeutic agent in preserving ovarian function under hypothyroid conditions.