Flaxseed Oil Alleviates PFOS-Induced Liver Injury\nby Regulating Hepatic Cholesterol Metabolism

Perfluorooctanesulfonate\n(PFOS) is a widespread, persistent environmental\npollutant that exerts apparent liver toxicity. Flaxseed oil (FO),\na dietary oil rich in α-linolenic acid, has been demonstrated\nto possess a diverse array of health benefits. However, whether FO\nprotects against PFOS-induced liver injury and its underlying mechanisms\nremain unclear. C57/BL6 mice were orally treated with different concentrations\nof FO alone or in combination with 10 mg/kg of PFOS for 28 consecutive\ndays. Blood and liver tissues were collected for proteomic, histopathological,\nbiochemical, immunohistochemical, and molecular examinations. Results\ndemonstrated that FO supplementation reduced PFOS-induced liver injury,\nas evidenced by a decrease in histopathological changes, serum transaminase\n(ALT and AST) levels, levels of oxidative stress, and inflammatory\ncytokine (TNF-α, IL-1β, and IL-6) levels. Proteomic analyses\nshowed that differentially expressed proteins were enriched in cholesterol\nmetabolic pathways when comparing the PFOS group to the FO supplementation\ngroups. The expression of cholesterol metabolism-related proteins\nwas also subsequently measured, revealing that FO supplementation\ndecreased the protein expressions of SREBP2, HMGCR, and LDLR while\nincreasing the expression of CYP7A1. This study demonstrates that\nFO can alleviate PFOS-induced hepatotoxicity by regulating hepatic\ncholesterol metabolism, indicating that FO may serve as an effective\ndietary intervention for preventing liver injury caused by PFOS.