Abstract

Herbicides make up a vital group of agricultural pesticides and represent a potential menace to human health. Butachlor (But), a widely used chloroacetamide herbicide to control weeds in crop fields, can cause environmental and health problems when used excessively. BAZ2B as a component of the nucleolar remodeling complex inhibits cell proliferation and induces mitochondrial dyshomeostasis. Here, we aim to explore the potential molecular mechanisms by which But induces cardiotoxicity and the unique role of BAZ2B in it. In this study, we found that But caused cardiomyocyte structural injury and mitochondrial impairment. But also inhibited mitochondrial biogenesis and induced mitochondrial stress accompanied by mitochondrial unfolded protein response, ultimately resulting in mitochondrial dysfunction. Moreover, But inhibited cell proliferation and accelerated cellular senescence. Of note, But up-regulated the expression of BAZ2B and activated the cGAS-STING pathway. These findings show that regulating the BAZ2B-mediated cGAS-STING pathway is a potential therapeutic method for preventing herbicide-induced cardiotoxicity.