MCPA-Na exposure in aquatic systems: disruption of pathways and increased susceptibility to infection in fish

MCPA-Na (2-methyl-4-chlorophenoxyacetic acid) is a selective herbicide widely used in agricultural cultivation. Despite monitoring indicating risks to aquatic life, the specific organ effects and pathogen susceptibility are unclear. Therefore, we constructed a "compound-core target-signaling pathway" network using network toxicology methods, and the results showed that MCPA-Na interacted with multiple organs of loach (including intestine, liver, kidney, heart, gills, skin and blood). STRING and Cytoscape software were used to screen the core targets: PPAR (Peroxisome proliferator-activated receptor), ACE (angiotensin converting enzyme), REN (Renin), and CA9 (carbonic anhydrase). KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the core targets of each tissue were significantly enriched in the renin-angiotensin system, NF-κB signaling pathway, adherens junctions and cholinergic synapses. The relationship between the toxicology and molecular markers of MCPA-Na was further explored by using animal experiments, and the susceptibility of Misgurnus anguillicaudatus (loach) to opportunistic pathogens after toxic exposure was simulated by using opportunistic pathogen challenge Aeromonas hydrophila (A. hydrophila). It was found that the compound induced oxidative stress and triggered intestinal inflammation and promoted apoptosis. These processes undermine the intestinal barrier and increase the susceptibility of loach to the A. hydrophila, thereby exacerbating the challenge of aquaculture food safety.