Ferrostatin 1 exerts multifaceted hepatic protection against alcoholic liver injury by inhibiting ferroptosis.

Abstract

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.