Coenzyme Q and Selenium Co-Supplementation Alleviate Methionine Choline-Deficient Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.

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.

Methods: 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.

Results: 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.

Conclusions: 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.