Network-based investigation of norfloxacin-induced nasal immune-related inflammatory responses in carp (Cyprinus carpio) and its cross-species implications for olfactory immune disturbance.

Abstract

Norfloxacin (NOR), a widely used fluoroquinolone antibiotic, has raised environmental concerns due to its persistent presence in aquatic ecosystems. This study integrates a common carp (Cyprinus carpio) model, network toxicology, and molecular docking to investigate the potential mechanisms of NOR-induced nasal inflammation. Common carp were exposed to environmentally relevant NOR concentrations, and histopathological, biochemical, and molecular analyses were conducted. Results revealed significant olfactory epithelial damage, including increased mucin secretion, oxidative stress, and apoptosis. Network toxicology analysis identified key target genes, including TNF, GSK3B, NFKB1, and HIF1A, associated with NOR-induced inflammatory responses. Molecular docking confirmed strong binding affinities between NOR and these targets, suggesting potential cross-species toxicity mechanisms. The predictions made by the ECOSAR software indicate that the toxicity of NOR degradation products is generally higher than that of the parent compound. This study highlights the immunotoxic and inflammatory effects of NOR on fish olfactory tissues and suggests implications for human health. The findings provide insights into the environmental risk assessment of fluoroquinolone antibiotics and underscore the necessity for stricter regulations on their use in aquaculture.