Alleviating Effect and Potential Mechanisms of Selenium Supplementation on Chronic Liver Injury Induced by Oxidized Soybean Oil

ABSTRACT Lipid oxidation can induce liver oxidative stress and lipotoxic damage, while selenium (Se) possesses detoxification, antioxidation, immunity, and liver protection functions. However, the effects of Se and oxidized lipids on liver oxidative stress and lipid metabolism, along with the underlying mechanisms, remain underexplored. This study aimed to investigate the protective effects of Se against liver injury induced by oxidized soybean oil (OSO) in mice. C57BL/6J mice (n = 60) were randomly divided into Control (0.2 mg/kg Se+7% fresh soybean oil), OSO (0.2 mg/kg Se+7% OSO), and OSO+Se (1.0 mg/kg Se+7% OSO) groups for 10 weeks. The results showed that Se supplementation mitigated the morphological structure and functional impairment, inflammation, and oxidative stress of the liver caused by OSO, and improved changes to the liver fatty acid profile and lipid metabolism disorders. It also reversed the OSO‐induced imbalance of liver polyunsaturated fatty acid metabolites and inhibited OSO‐induced activation of the PI3K‐AKT pathway. Se may activate the Nrf2 pathway and inhibit the PI3K‐AKT pathway to improve inflammation, oxidative stress, and fatty acid metabolism disorders, thereby reducing liver injury. These findings highlight the nutritional relevance of Se as a potential therapeutic agent for preventing liver damage from oxidized lipids.