Proteomics-Based Exploration of the Hepatoprotective Mechanism of α-Lipoic Acid in Rats with Iron Overload-Induced Liver Injury

作者：Shuxia Jiang, Yujia Shu, Shihui Guo, Yingdong Ni, Ruqian Zhao, Hongli Shan, Wenqiang Ma · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26104774 · 被引用次数：5 · 研究领域：Biochemical Acid Research Studies、Metabolism and Genetic Disorders、Alcoholism and Thiamine Deficiency

Excessive iron accumulation poses a significant threat to liver health, primarily through oxidative stress and autophagy dysregulation. α-Lipoic acid (ALA), a natural antioxidant with hepatoprotective properties, may alleviate iron-induced liver damage, but its underlying mechanisms are not fully understood. This study utilized male Sprague Dawley rats and BRL-3A cells to explore the protective effects of ALA against iron overload in vivo and in vitro, respectively. ALA treatment significantly reduced hepatic iron accumulation, improved liver morphology, and alleviated iron-induced ultrastructural damage in rats. ALA also improved liver function markers in plasma, including alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), and the AST/ALT ratio. Furthermore, ALA mitigated iron-induced oxidative stress by lowering hepatic reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the antioxidant enzyme activities of glutathione peroxidase (GSH-Px) and catalase (CAT). In BRL-3A cells, ALA improved cell viability, decreased intracellular ROS, and reduced iron levels. Proteomics analysis indicates that NAD(P)H: quinone oxidoreductase 1 (NQO1) may play a critical role in the protective effects of ALA against iron overload-induced hepatic damage in rats. Mechanistically, ALA upregulated NQO1 expression while downregulating autophagy-related proteins, including light chain 3B (LC3B), lysosomal-associated membrane protein 1 (LAMP1), a...