Resveratrol-loaded liposomes regulate mitochondrial oxidative stress through the HIGD1A/NF-κB/SOD2 signaling pathway to improve chemotherapy-induced ovarian injury.

BACKGROUND

Chemotherapy-induced ovarian damage poses a serious threat to female fertility and reproductive health, but effective and specific intervention methods remain lacking.

METHODS

Resveratrol liposomes was prepared using the thin-film evaporation-high-pressure homogenization method, and its particle size, PDI, zeta potential, and encapsulation efficiency were characterized. A CTX-induced ovarian injury model was established, with mice randomly divided into five groups: control group, model group, positive group, free resveratrol group, and resveratrol liposomes treatment group. Ovarian function and mechanisms were evaluated through HE staining, hormone assays, oxidative stress indicators, mitochondrial membrane potential detection, western blot, immunohistochemistry, and TUNEL staining.

RESULTS

The study found that Res-Lipo treatment significantly improved ovarian tissue morphology, reversed the decrease in serum AMH and increase in FSH caused by CTX. Additionally, resveratrol liposomes specifically upregulated the expression of HIGD1A protein in ovarian tissue, inhibited the phosphorylation and nuclear translocation of NF-κB p65, while also elevating SOD2 protein levels. Consequently, it markedly enhanced ovarian antioxidant enzyme activity, reduced oxidative stress, improved mitochondrial membrane potential, and decreased ovarian granulosa cell apoptosis.

CONCLUSION

This study confirms that resveratrol liposomes can effectively alleviate chemotherapy-induced ovarian mitochondrial oxidative stress damage and dysfunction by activating HIGD1A, inhibiting NF-κB overactivation, and upregulating SOD2 expression.