Chlorfenapyr Induces Cardiotoxicity by Downregulating Dap3 to Induce Mitochondrial Damage

Abstract

Background: Chlorfenapyr (Chlo) is a pyrrole-based insecticide. It has proven effective in controlling a range of pests. This study examined the impact of Chlo on myocardial mitochondrial injury in mice and the underlying mechanisms involved. Methods: C57BL/6 mice were categorized into groups of saline, doxorubicin (DOX), and low, medium, and high doses of Chlo. The cardiac function of the mice in each group was evaluated using cardiac biomarkers. Hematoxylin and eosin (HE) staining was employed to observe changes in the myocardial tissue, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect cardiomyocyte apoptosis. Proteins associated with mitochondrial damage were identified by western blotting. Furthermore, cardiomyocytes were isolated and divided into the Dimethyl sulfoxide (DMSO) group, medium and low Chlo groups, DOX group, and Chlo group. Transmission electron microscopy (TEM) was utilized to investigate the mitochondria, and the mitochondrial membrane potential was analyzed using a JC-1 kit. Lactate dehydrogenase (LDH) and reactive oxygen species (ROS) secretion were quantified to evaluate oxidative stress. Results: The results indicate that Chlo can impair cardiac function in vivo (p < 0.01). Chlo leads to a marked decrease in the mitochondrial membrane potential, resulting in mitochondrial damage (p < 0.05). In cardiomyocytes, Chlo significantly downregulates death-associated protein 3 (Dap3) expression (p < 0.01). However, overexpression of Dap3 effectively mitigated the oxidative stress, apoptosis, and mitochondrial damage induced by Chlo in cardiomyocytes (p < 0.05). Conclusions: Overall, high concentrations of Chlo trigger cardiotoxicity by downregulating Dap3, leading to mitochondrial damage.