Amelioration of arsenic-induced hepatic injury via sulfated glycosaminoglycan from swim bladder: Modulation of Nrf2 pathway and amino acid metabolism.

Arsenic, a known environmental pollutant with a carcinogenic risk, is associated with chronic liver toxicity. Prebiotic regulation represents an emerging dietary strategy to alleviate arsenic-induced hepatotoxicity; however, research in this area remains limited. This study employed sulfated swim bladder glycosaminoglycan (SBSG), a potential prebiotic, to assess its efficacy in mitigating arsenic-induced liver injury. In basic indicators, SBSG resisted oxidative stress by down-regulating AST, ALT, MDA, and MPO, up-regulating antioxidants (T-SOD, GSH, and GSH-px), and ameliorating histopathological damage. RT-qPCR analysis revealed that SBSG could regulate the Nrf2 signaling pathway and affect the expression of o genes related to ferroptosis and detoxification. The expression of protein further verified that SBSG could play an antioxidant and detoxifying role as an Nrf2 activator. Non-targeted metabolomics results demonstrated that SBSG primarily addresses metabolic disorders by up-regulating D-amino acid metabolism, ABC transporter, and alanine, aspartate and glutamate metabolism. Correlation analysis suggests that SBSG alleviates arsenic-induced liver oxidative damage through mechanisms linked to the Nrf2 pathway and amino acid metabolism. This study provided a research basis for expanding the dietary strategy to reduce arsenic induced toxicity.