Exposure to Polypropylene Microplastics Causes Cardiomyocyte Apoptosis Through Oxidative Stress and Activation of the <scp>MAPK</scp>‐Nrf2 Signaling Pathway

Microplastics are a growing concern as pollutants that impact both public health and the environment. However, the toxic effects of polypropylene microplastics (PP-MPs) are not well understood. This study aimed to investigate the effects of PP-MPs on cardiotoxicity and its underlying mechanisms. The cardiotoxicity of exposure to different amounts of PP-MPs were investigated in both ICR mice and H9C2 cells. Our results demonstrated that sub-chronic exposure to 5 and 50 mg/L PP-MPs led to myocardial structural damage, apoptosis, and fibrosis in mice cardiomyocytes. Flow cytometry analysis revealed that PP-MPs could decrease mitochondrial membrane potential and induce apoptosis in H9C2 cells. Western blotting revealed decreased expression of Bcl-2, poly(ADP-ribose) polymerase (PARP) and caspase 3 and increased expression of Bax, cleaved-PARP, and cleaved-caspase 3 in PP-MPs-treated cardiac tissue and H9C2 cells. These results confirmed the apoptotic effects induced by PP-MPs. Moreover, PP-MPs treatment triggered oxidative stress, as evidenced by the increased levels of malondialdehyde; reduction in glutathione peroxidase, superoxide dismutase, and catalase activities in mice cardiac tissues; and increased reactive oxygen species levels in H9C2 cells. Finally, western blotting demonstrated that exposure to PP-MPs significantly reduced the expression levels of Nrf2 and p-ERK proteins associated with MAPK-Nrf2 pathway in both cardiac tissue and H9C2 cells. Overall, our findings indicate that PP-MPs can induce cardiomyocyte apoptosis through MAPK-Nrf2 signaling pathway, which is triggered by oxidative stress. This study provides a foundation for determining the effects of PP-MPs on cardiotoxicity and their underlying mechanisms.