Microplastics induced inflammation and apoptosis via ferroptosis and the NF-κB pathway in carp.

Microplastics (MPs), a new class of pollutant that threatens aquatic biodiversity, are becoming increasingly prevalent around the world. Fish growth may be severely inhibited by microplastics, resulting in severe mortality. Exposure to microplastics increases the likelihood of intestinal injuries, but the underlying mechanisms remain equivocal. The objective of this study was to investigate the potential toxic mechanisms underlying microplastic-induced intestinal injury in fish and to assist researchers in identifying novel therapeutic targets. In this study, a model of carp exposed to microplastics was established successfully. Histological observation showed that exposure to polyethylene microplastics caused damage to the intestinal mucosal surface and a significant increase in goblet cells, which aggregated on the surface of the mucosa. The mucosal layer was observed to fall off. Lymphocytes in the intestinal wall proliferated and aggregated. TUNEL staining showed that apoptosis occurred in the group exposed to microplastics. The qPCR results showed that the expression of Ferroptosis apoptotic factors COX-2 and ACSL4 was upregulated, while the expression of TFRC, FIH1, SLC7A11, and GPX4 was downregulated. The NF-κB pathway (p-p65, IκBα), inflammatory cytokines (TNF-α, IL-8, IL-6) and apoptosis genes (Bax, Caspase3) were upregulated. Semi-quantitative detection of related proteins by Western blotting was consistent with the gene expression results. In addition, the ELISA assay showed that lipid peroxidation and inflammatory cytokines (TNF-α, IL-1β, IL-6) were increased in the microplastic exposed group. To conclude, lipid peroxidation induced by microplastics activates the NF-κB pathway and causes ferroptosis, ultimately resulting in intestinal damage and cellular apoptosis.