Metformin mitigates cisplatin-induced premature ovarian insufficiency via Sirt1/Nrf2 activation

Premature ovarian insufficiency (POI) occurs in young women who receive chemotherapy, with cisplatin being the known culprit. Cisplatin-induced ovarian damage associated with POI results from oxidative stress. Metformin, a widely prescribed drug for type 2 diabetes, plays an important role in the mitigation of oxidative stress. However, the precise mechanism through which metformin protects against cisplatin-induced POI remains unclear. Hence, this study aimed to investigate the protective effects of metformin against cisplatin-induced granulosa cell (GCs) damage and explore the underlying anti-oxidative stress mechanisms.

In this study, an in vitro POI model was established using cisplatin-treated human GCs. Metformin pretreatment was used to assess the effects of metformin on damaged GCs. Cell viability and hormone levels were measured using CCK8 and enzyme-linked immunosorbent assay, respectively. The mechanisms of oxidative stress repair by metformin were evaluated using flow cytometry, western blot analysis, and quantitative real-time polymerase chain reaction.

Metformin pretreatment significantly enhanced GC viability, reduced apoptosis, decreased reactive oxygen species levels, improved mitochondrial function, and increased superoxide dismutase activity. Additionally, metformin upregulated the expression of Bcl-2, Sirt1, and Nrf2, while downregulating Bax, indicating its protective role through the activation of the Sirt1/Nrf2 signaling pathway.

Metformin may serve as a promising therapeutic agent to prevent POI by mitigating oxidative stress and apoptosis.