Abstract

Glufosinate ammonium (GLA) residues in water threaten aquatic organisms and pose ecological risks to aquaculture. Current understanding of the molecular mechanisms driving GLA-induced hepatotoxicity in aquatic species remains incomplete, with effective intervention strategies still lacking. This study aims to elucidate the molecular mechanisms underlying hepatotoxicity GLA in grass carp, and to evaluate the intervention effects of activating the cholinergic anti-inflammatory pathway (CAP). Herein, the toxicokinetic characteristics revealed that GLA is highly hydrophilicity and suitable intestinal transmembrane ability. GLA exposure cause liver structure damage in grass carp, manifested as diffuse hydropic degeneration, cytoplasmic pallor, inflammatory cell infiltration and hepatocyte apoptosis. Integration of network toxicology and transcriptomics analysis show suggest that GLA-induced hepatitis can synergistically disrupt amino acid and glutathione metabolic homeostasis through the core genes cystathionine-gamma lyase and phosphoribosyl transferase domain containing 1. In vitro and in vivo experiments have confirmed that activating CAP can reverse GLA induced liver inflammatory damage, inhibit mitochondrial damage and cellular autophagy. In summary, activation of CAP can mitigate GLA-induced hepatotoxicity in grass carp through the suppression of inflammatory responses and mitochondrial dysfunction. This study elucidates the toxic mechanism of GLA on aquatic organisms, providing a theoretical basis for the risk prevention and control of GLA pollution in freshwater aquaculture.