Choi Hyewon, Choi Jiwon, Go Yula, Chung Jayong
Department of Food & Nutrition, Kyung Hee University, Seoul 02447, Republic of Korea.
Nutrients. 2025 Jan 9;17(2):229. doi: 10.3390/nu17020229.
BACKGROUND/OBJECTIVES: The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and Se in ameliorating MASH induced by a methionine choline-deficient (MCD) diet in mice.
C57BL/6J male mice were fed either a methionine choline-sufficient (MCS) or MCD diet and treated with vehicle, CoQ (100 mg/kg), Se (158 μg/kg), or their combination (CoQ + Se) for 4 weeks.
The MCD diet significantly increased hepatic steatosis, inflammation, and fibrosis compared to MCS controls. Treatment with CoQ and Se, particularly in combination, markedly reduced the MAFLD activity score, hepatic inflammation, and fibrosis. Combined supplementation of CoQ and Se significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels and hepatic TG and cholesterol concentrations. CoQ and Se effectively mitigated hepatic oxidative stress by enhancing catalase and superoxide dismutase activities, increasing glutathione peroxidase (GPX) activity, and restoring the GSH/GSSG ratio. Lipid peroxidation markers, such as malondialdehyde and 4-hydroxynonenal, were significantly reduced. Furthermore, the expression of ferroptosis-related markers, including acyl-CoA synthetase long-chain family member 4, arachidonate 12-lipoxygenase, and hepatic non-heme iron content, was significantly downregulated, while GPX4 expression was upregulated by combined CoQ and Se treatment.
CoQ and Se synergistically alleviate MASH progression by reducing oxidative stress and lipid peroxidation, which may contribute to the suppression of ferroptosis. Combined CoQ and Se supplementation demonstrates therapeutic potential for managing MASH and related liver injury.
背景/目的：代谢功能障碍相关脂肪性肝炎（MASH）的发病机制与氧化应激增加和脂质过氧化密切相关。辅酶Q（CoQ）和硒（Se）是公认的具有抗氧化作用、可抵御氧化损伤的物质。本研究旨在探讨CoQ和Se对改善蛋氨酸胆碱缺乏（MCD）饮食诱导的小鼠MASH的作用。
将C57BL/6J雄性小鼠分为两组，分别给予蛋氨酸胆碱充足（MCS）饮食或MCD饮食，并给予溶剂对照、CoQ（100 mg/kg）、Se（158 μg/kg）或它们的组合（CoQ + Se）处理4周。
与MCS对照组相比，MCD饮食显著增加了肝脏脂肪变性、炎症和纤维化。CoQ和Se处理，尤其是联合处理，显著降低了MAFLD活动评分、肝脏炎症和纤维化。联合补充CoQ和Se显著降低了血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平以及肝脏甘油三酯和胆固醇浓度。CoQ和Se通过增强过氧化氢酶和超氧化物歧化酶活性、提高谷胱甘肽过氧化物酶（GPX）活性以及恢复谷胱甘肽/氧化型谷胱甘肽比值，有效减轻了肝脏氧化应激。丙二醛和4-羟基壬烯醛等脂质过氧化标志物显著降低。此外，CoQ和Se联合处理显著下调了铁死亡相关标志物的表达，包括酰基辅酶A合成酶长链家族成员4、花生四烯酸12-脂氧合酶和肝脏非血红素铁含量，同时上调了GPX4的表达。
CoQ和Se通过降低氧化应激和脂质过氧化协同减轻MASH进展，这可能有助于抑制铁死亡。联合补充CoQ和Se显示出治疗MASH及相关肝损伤的潜力。
