Hydramethylnon-induced autophagy and apoptosis in human bronchial epithelial cells by homeostatic changes

Household chemicals are commonly used products worldwide; however, their effects on human respiratory health are poorly understood. In this study, we aimed to investigate the effects of hydramethylnon (HDM), an insecticide frequently found in household products, on human bronchial epithelial cells (BEAS-2B) using in vitro experiments. The cells were exposed to varying concentrations of HDM (range, 1-4 µg/mL) for 24 h, followed by the evaluation of cell viability, apoptotic markers, metabolite levels, and antioxidant levels. The results showed that HDM exposure significantly increased oxidative stress by elevating the levels of reactive oxygen species, leading to the autophagosome accumulation and impaired autophagic flux (manifested by increased LC3B and p62 levels) and apoptosis (detected by increased cleaved caspase-3 and Bax/Bcl-2 levels and cytochrome c release). Flow cytometry confirmed that dose-dependent apoptotic cell death was further enhanced by chloroquine, an autophagy inhibitor. HDM exposure also resulted in a dose-dependent decrease in the messenger RNA levels of antioxidant enzymes, including catalase and glutathione peroxidase, and notable disruptions in sulfur-containing metabolites, including decreased levels of S-adenosylmethionine, S-adenosylhomocysteine, taurine, and glutathione. These metabolic perturbations were significantly aggravated by autophagy inhibition, suggesting autophagy-lysosome pathway plays a protective role against HDM-induced oxidative damage. These results suggest that HDM exposure poses substantial risks to human respiratory health through the oxidative stress-mediated disruption of antioxidant defense systems and metabolic pathways, ultimately impaired autophagic flux and mitochondria-mediated apoptosis in bronchial epithelial cells. This study highlights the need for improved safety guidelines and risk assessments of human inhalation exposure to household insecticides, particularly HDM.