Combined effects of polyvinyl chloride or polypropylene microplastics with cadmium on the intestine of zebrafish at environmentally relevant concentrations

Cadmium (Cd) is a common additive in polyvinyl chloride (PVC) and polypropylene (PP) plastics. Aquatic organisms were inevitably co-exposed to PVC/PP microplastics (MPs) and Cd, but their combined toxicity is still unknown. In this study, adult zebrafish were exposed to 200 μg/L MPs (PVC or PP) and 10 μg/L Cd alone or in combination for 28 days to investigate their toxicity and mechanisms. Results showed that combined exposure with PVC/PP enhanced the Cd accumulation in the zebrafish intestine. Subsequently, toxicology analyses showed that both PVC and PP possessed synergistic toxicity with Cd, manifested by the exfoliation and necrosis of intestinal epithelial cells, and increased levels of interleukin-1β (IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA). PP exhibited a stronger synergistic effect than PVC. Integration of non-targeted metabolomics and 16S rRNA gene sequencing revealed that combined exposure to PVC and Cd induced intestine toxicity mainly through bile acid (BA) biosynthesis, fructose (Fru) and mannose (Man) metabolism, and pentose phosphate pathway (PPP). The combined exposure of PP and Cd induced toxicity through the arginine (Arg) and glutathione (GSH) metabolisms. Meanwhile, combined exposure of PVC/PP and Cd increased the abundance of intestinal Proteobacteria and pathogen Vibrio, and decreased the abundance of Gemmobacter. These changes indrectly promoted the synergistic toxicity of PVC/PP and Cd through metabolites, such as indole-3-pyruvate (IPyA), chenodeoxycholic acid (CDCA), and cholic acid (CA). These findings highlighted that more attention should be paid to the toxicity of chemicals at environmentally relevant concentrations, particularly those co-existing with MPs.