Selenomethionine Alleviates Alcohol-Induced Liver Injury by Inhibiting Ferroptosis.

Abstract

Background and aim: Selenomethionine (Se-Met) has been reported to reduce oxidative stress (OS) and hepatic injury; however, its role in alcoholic liver disease (ALD), particularly with ferroptosis, remains poorly understood.

Methods: Oxidative stress was induced using ethanol, and ferroptosis was inhibited with ferrostatin-1 (fer-1) in L-02 and LX2 cell lines, respectively. The effects of Se-Met on alcohol-induced hepatocyte damage were evaluated in vitro by examining cell viability, lipid peroxidation, and the level of key ferroptosis-associated markers. In vivo, the interaction between Se-Met and ferroptosis was examined via an ALD mouse model through analyses of liver histology, lipid peroxidation, liver function, and ferroptosis-related indices.

Results: In vitro and in vivo experiments indicated that both Se-Met and fer-1 have a significant protective role against alcohol-induced hepatocyte death and liver injury. Treatment with Se-Met or fer-1 can promote hepatocyte proliferation, ameliorate the typical symptoms of lipid peroxidation (e.g., glutathione depletion, superoxide dismutase enzyme activity, intracellular reactive oxygen species (ROS) level, malonaldehyde (MDA) content), and altered the expression of ferroptosis-related factors. Moreover, the findings indicated that the administration of Se-Met or fer-1 significantly ameliorated the pathological alterations and improved liver function indices associated with alcohol-induced liver damage in mice. These effects may collectively suppress the deleterious impact of ethanol on hepatic tissue.

Conclusion: This study concluded that the ferroptosis pathway regulated alcohol-induced hepatocyte injury. The administration of selenomethionine protects ALD by partially inhibiting the ferroptosis pathway, providing a novel therapeutic approach for ALD.