Microcystis aeruginosa-driven acute toxicity compromises immune-metabolic regulation and hepatocyte integrity in grass carp.

Harmful Microcystis aeruginosa blooms represent a major risk to aquaculture sustainability. The present study mainly examined M. aeruginosa-induced liver injury in grass carp and the associated cytotoxic effects observed in L8824 cells. Histological analysis revealed dose-dependent hepatic injury in grass carp, manifested by vacuolar degeneration, inflammatory infiltration, and architectural disorganization. Metabolomic analysis revealed that M. aeruginosa exposure induced marked hepatic metabolic remodeling, primarily involving glyoxylate and dicarboxylate metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism, accompanied by altered levels of representative metabolites such as glutaric acid, Hepoxilin B3, and D-galactose-related metabolites. Additionally, correlation analysis revealed coordinated transcriptional-metabolic alterations, with IL-4 positively associated with 4-guanidinobutanoic acid, IL-12 inversely associated with muramic acid, and apoptosis-related genes negatively associated with D-ornithine and Hepoxilin B3. Notably, in vitro analyses showed that exposure to M. aeruginosa led to a concentration- and time-dependent reduction in L8824 cell viability and an increase in late apoptosis. Concomitantly, elevated ROS levels, attenuated antioxidant enzyme activities, and mitochondrial membrane potential collapse were observed, pointing to oxidative apoptosis driven by mitochondrial dysfunction. In summary, M. aeruginosa triggers liver injury in grass carp by driving oxidative stress, inflammation, apoptosis, and metabolic imbalance.