Tanshinone ⅡA alleviates cisplatin-induced ovarian damage in mice by inhibiting ferroptosis

AimTo explore the protective effect of tanshinone ⅡA (Tan) on cisplatin-induced ovarian function damage in mice and to reveal the underlying mechanism.MethodsThirty female C57BL/6 mice were randomly and evenly allocated into the control group, model group, and Tan intervention group. The model was established by continuously intraperitoneal injection of cisplatin (2 mg·kg-1) for four weeks. The Tan intervention group received intragastric administration of Tan (25 mg·kg-1) 1 h before cisplatin injection. The estrous cycle, ovarian morphology, follicle count, serum hormone (E2, FSH) levels and ferroptosis indicators (iron ions, 4-HNE, MDA, SOD) in ovarian tissues of mice were evaluated. The expression profiles of ferroptosis-related molecules (Tfrc, Nrf2, GPX4, SLC7A11) in ovarian tissues were detected.ResultsCompared with the control group, the ovarian function of mice in the model group was significantly impaired. Compared with the model group, the ovarian atrophy, ovarian index, and estrous cycle of the Tan intervention group were improved; the number of growing follicles increased, and the number of atretic follicles decreased; serum E2 increased, FSH decreased; the contents of iron ions, 4-HNE, and MDA in ovarian tissue decreased, and the SOD activity increased; Tfrc expression was down-regulated, and the expressions of Nrf2, GPX4, and SLC7A11 were up-regulated.ConclusionsTan alleviates cisplatin-induced ovarian functional impairment and hormonal imbalance in mice, potentially through activation of the Nrf2 signaling pathway, upregulation of GPX4 and SLC7A11 expression, and inhibition of ferroptosis.