Astaxanthin Alleviates Lead-Induced Toxicity by Restoring Hepatic and Gut-Liver Axis Homeostasis Through Multi-Dimensional Metabolic and Antioxidative Pathways

This study explores the hepatoprotective and systemic protective effects of astaxanthin (ATX) against lead-induced toxicity in a mouse model, emphasizing its regulatory roles in oxidative stress, inflammation, metabolism, and gut-liver axis homeostasis. Supplementation with ATX in various doses significantly alleviated lead-induced physiological and biochemical disruptions, including weight loss, hepatic and renal damage, and metabolic imbalances. Metabolomic and transcriptomic analyses revealed that ATX functioned crucially in restoring redox homeostasis, regulating lipid, amino acid, and nucleotide metabolism, and activating critical pathways such as Nrf2/ARE, PPAR, and S1P, thereby enhancing antioxidative, anti-inflammatory, and detoxification capacities. ATX also modulated gut microbiota by promoting beneficial bacterial populations, suppressing harmful strains, and increasing short-chain fatty acid production, effectively restoring gut-liver axis balance. These findings demonstrate that ATX confers comprehensive protection against lead toxicity via multi-dimensional regulatory mechanisms, highlighting ATX as a promising therapeutic agent for heavy metal poisoning. Further research is warranted to validate clinical applications of ATX and evaluate its long-term safety.