Intravenous Exposure to Amino-polystyrene Induces Excessive Autophagy and Apoptosis in Myocardium Through ROS Driven PI3K/AKT/mTOR Axis.

摘要

Polystyrene (PS) is a pervasive plastic whose threat to human health is growing, yet its cardiotoxicity, particularly under clinically relevant exposure scenarios, remains poorly understood. This study addresses this critical gap by modeling intravenous exposure to nanopolystyrene, simulating clinical situations where plastic-derived medical devices directly contact blood. We established an in vitro model using human AC16 cardiomyocytes and an in vivo model via tail vein injection in Balb/c mice to compare the effects of amino-modified (PS-NH₂), carboxyl-modified (PS-COOH), and unmodified (PS-Bare) polystyrene nanoparticles. Our findings demonstrate that PS-NH₂, in contrast to PS-COOH and PS-Bare, induces significant cardiotoxicity. This toxicity was initiated by a substantial increase in reactive oxygen species (ROS), which subsequently suppressed the PI3K/AKT/mTOR signaling axis. This inhibition led to the excessive activation of autophagy and the induction of apoptosis in cardiomyocytes. In vivo, PS-NH₂ exposure caused severe pathological changes in mouse hearts, confirming its potent cardiotoxicity, characterized by inflammation, an impaired oxidative-antioxidant balance, and adverse cardiac remodeling. Notably, these detrimental effects were substantially reversed by the ROS scavenger N-acetylcysteine (NAC) or ginsenoside Rb1. In conclusion, our study reveals that Polystyrene positively charged amino-modified during degradation is the key to its cardiotoxicity, operating through a ROS-driven PI3K/AKT/mTOR pathway. These findings underscore the potential risks associated with specific surface modifications of nanoplastics and provide crucial insights for developing therapeutic strategies against plastic-induced cardiac injury.