College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China.
College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong Province, China.
Lipids. 2023 Sep;58(5):229-240. doi: 10.1002/lipd.12377. Epub 2023 Aug 7.
Alcoholic liver disease (ALD) is a significant risk factor in the global disease burden. The antioxidants vitamin C (Vc) and N-acetyl cysteine (NAC) have shown hepatoprotective effects in preventing and treating ALD. However, the correlation between the improved effect of antioxidants and lipid metabolism is still unclear. In this study, AML12 cells and C57BL/6 mice stimulated with alcohol were used to investigate the protective effects and potential mechanisms of two antioxidants (Vc and NAC) on alcoholic liver injury. Results showed that Vc and NAC attenuated intracellular lipid accumulation and oxidative damage induced by excessive alcohol exposure in hepatic AML12 cells. The in vivo results indicated that antioxidants ameliorated alcohol-induced changes in histopathology, reducing the levels of alcohol metabolizing factors and aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) contents, which demonstrated that antioxidants effectively mitigated liver injury in ALD mice. Further studies showed that antioxidants reversed the disruption of fatty acid (FA) synthesis and lipid transport induced by alcohol exposure, and restored phospholipid levels. Especially, Vc and NAC increased the endogenous antioxidant plasmenyl phosphatidylethanolamine (PlsEtn). Additionally, antioxidants ameliorated the alcohol-impaired mitochondrial function and inhibited excessive oxidative stress. In conclusion, antioxidants can regulate lipid metabolism and phospholipid homeostasis, which in turn inhibit oxidative stress and thereby exert protective effects against ALD.
酒精性肝病 (ALD) 是全球疾病负担的一个重要危险因素。抗氧化剂维生素 C (Vc) 和 N-乙酰半胱氨酸 (NAC) 在预防和治疗 ALD 方面显示出了肝保护作用。然而，抗氧化剂改善效果与脂质代谢之间的相关性仍不清楚。在这项研究中，使用酒精刺激的 AML12 细胞和 C57BL/6 小鼠来研究两种抗氧化剂 (Vc 和 NAC) 对酒精性肝损伤的保护作用及其潜在机制。结果表明，Vc 和 NAC 减轻了肝 AML12 细胞中过量酒精暴露引起的细胞内脂质积累和氧化损伤。体内结果表明，抗氧化剂改善了酒精引起的组织病理学变化，降低了酒精代谢因子和天冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶 (ALT)、甘油三酯 (TG) 和总胆固醇 (TC) 的水平，表明抗氧化剂有效减轻了 ALD 小鼠的肝损伤。进一步的研究表明，抗氧化剂逆转了酒精暴露引起的脂肪酸 (FA) 合成和脂质转运的破坏，并恢复了磷脂水平。特别是，Vc 和 NAC 增加了内源性抗氧化剂血浆磷脂酰乙醇胺 (PlsEtn)。此外，抗氧化剂改善了酒精损害的线粒体功能并抑制了过度的氧化应激。总之，抗氧化剂可以调节脂质代谢和磷脂稳态，从而抑制氧化应激，从而对 ALD 发挥保护作用。
