While ferroptosis is implicated in alcoholic liver disease, its precise mechanisms of action are not fully defined. This study aims to investigate the protective role of the ferroptosis inhibitor Ferrostatin-1 (Fer-1) against alcoholic liver injury, exploring its underlying mechanisms. Using mice models of acute and chronic ethanol exposure, we assessed the effects of Fer-1. We evaluated liver function, histopathological damage, and key molecular markers related to ferroptosis, metabolism, and inflammation. Fer-1 significantly improved liver function and alleviated tissue damage, including lipid accumulation and fibrosis. It enhanced antioxidant capacity and reduced iron overload, oxidative stress, and lipid peroxidation. Furthermore, Fer-1 improved dysregulated iron and lipid metabolism and attenuated inflammation. Notably, these protective effects appear to be independent of the Nrf2/HO-1 pathway, autophagy, and NLRP3 inflammasome. Fer-1 exerts multi-faceted protection against alcoholic liver injury by specifically inhibiting ferroptosis. It blocks the vicious cycle of alcohol-induced metabolic imbalances, oxidative stress, and inflammation, offering new potential strategies for treating alcoholic liver disease.
Yu et al. (Sun,) studied this question.