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.
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Acknowledgements
This work was supported by Yunnan Provincial Clinical Medicine Center for Digestive System Diseases (2024YNLCYXZX0111), and Yunnan Fundamental Research Projects (202301AU070167). Yunnan Labreal Biotechnology Co.,Ltd provided the research materials for the animal experiment. Although the animal experiment was performed on a private company’s platform, the company did not participate in writing, reviewing, and publishing this manuscript. No economic interests were revealed. We are grateful to Hui Li and the experimental animal team of the Yunnan Labreal Biotechnology Co.,Ltd for providing technical support in constructing the mice model for this work.
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Conceptualization, Y.L.; methodology, Y.L. and S.Z.; Investigation, Z.H., W.Y., X.L., Z.X., and L.Y.; Software Z.H., W.Y., and Z.A.; Writing—original draft, Y.L. and Z.H.; Writing—review & editing, S.Z.; Funding acquisition, Y.L.; Supervision, S.Z.
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Yu, L., Zhang, H., Wang, Y. et al. Ferrostatin 1 exerts multifaceted hepatic protection against alcoholic liver injury by inhibiting ferroptosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39849-x
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DOI: https://doi.org/10.1038/s41598-026-39849-x
