Evaluation of Pyrene Induced Cardiotoxicity Using Dual-Cardiotoxicity Evaluation Method

Pyrene (Pyr), a representative subtype of polycyclic aromatic hydrocarbons, is primarily generated during the incomplete combustion of organic matter. As an environmental pollutant, Pyr has been reported to exert adverse effects on various physiological systems. However, data regarding its cardiotoxicity remain limited. In this study, we investigated the acute cardiotoxic effects of Pyr using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were exposed to various doses of Pyr, and both cell viability and functional parameters were evaluated. Pyr did not affect cell viability under 30-minute and 2-hour exposure conditions regardless of dose. However, significant differences were observed in the dual-cardiotoxicity evaluation based on a microelectrode array, which allows simultaneous assessment of electrophysiological signals and contractility in CMs. Pyr decreased beat period and field potential duration in a dose-dependent manner, resembling the acute cardiotoxicity pattern of I_Kr and I_CaL channel blockers, and progressively reduced spike amplitude over time. Pyr also progressively reduced spike amplitude over time. Although a transient decrease in beat amplitude was observed at high dose, it recovered over time, while the excitation-contraction delay was reduced. Taken together, these findings demonstrate that Pyr can induce functional cardiotoxicity even under acute exposure and highlight the value of the established evaluation method for the development of safer alternative substances.