Co-exposure to cadmium and microplastics promotes liver fibrosis through the hemichannels -ATP-P2X7 pathway

Abstract

Abstract Background The widespread use of plastic products and the imperfection of plastic recycling systems have led to a continuous increase in microplastics (PS) in the environment. Microplastics have an adsorption effect and can act as carriers for other pollutants in the environment. Cadmium (Cd) is a heavy metal that interacts with microplastics. However, the potential toxicity of co-exposure of cadmium and microplastics to the body is not clear. This study focuses on the effects of co-exposure to cadmium and microplastics on liver fibrosis and its mechanism. Results In this study investigated, Cd+PS exposure increased superoxide anion production and promoted extracellular ATP release compared with exposure to Cd or PS alone. Cd+PS increased inflammatory cell infiltration, activated the P2X7-NLRP3 signaling pathway, and promoted inflammatory factor release. Cd+PS aggravated Cd- or PS-induced liver fibrosis and induced liver inflammation. In AML12/HSC-T6 cell in vitropoisoning model, exposure of AML12 cells to Cd+PS increased the opening of connexin hemichannels and promoted extracellular ATP release. Treatment of HSC-T6 cells with the supernatant of AML12 cells exposed to Cd+PS significantly promoted HSC-T6 cell activation. Treatment of HSC-T6 cells with different concentrations of ATP produced similar results. TAT-Gap19TFA, an inhibitor of connexin hemichannels, significantly inhibited the ATP release and activation of Cd+PS-treated HSC-T6 cells. Finally, the expression of the ATP receptor P2X7 was silenced in HSC-T6 cells, which significantly inhibited their activation. Conclusion Cadmium and microplastics have a synergistic toxic effect on the liver, destroy the microenvironment in the liver, and promote the development of liver fibrosis through the hemichannel-ATP-P2X7 signaling pathway. Our study reveals the impact of co-exposure to cadmium and microplastics on chronic liver diseases, providing a theoretical basis for disease prevention and treatment.