Resveratrol-pretreated ADSC-CM alleviates liver oxidative damage in mice by mediating the Sirt1/Nrf2 axis

Chronic liver injury is a prevalent pathological condition. Adipose-derived stem cell-conditioned medium (CM) has demonstrated efficacy in attenuating liver injury. Resveratrol (Res) pretreatment enhances the therapeutic effect of ADSCs, but whether it can enhance the protective effect of CM against CCl₄-induced liver injury is unknown. Therefore, we investigated the effects of CM and Res-pretreated adipose-derived stem cell-conditioned medium (R-CM) on liver structure, fibrosis, proliferation, oxidative stress, and mitochondrial pathway apoptosis in CCl₄-injured mice and further explored the underlying regulatory mechanism of the antioxidant effects of Res on CM. These findings indicated that R-CM was more effective than CM in mitigating CCl₄-induced liver injury, fibrosis, oxidative stress, and apoptosis. Moreover, we found that Res enhances the antioxidant capacity of CM by mediating the Sirt1/Nrf2 axis. Overall, our study demonstrated that CM derived from ADSCs could alleviate CCl₄-induced hepatic oxidative stress, and we found that Res could increase the antioxidant capacity of CM, which is closely related to the regulation of the Sirt1/Nrf2 pathway.