Dodecyldimethylamine oxide may induce lysosomal-associated cell death: Potential lipotoxicity

Dodecyldimethylamine oxide (DDAO) is one of the most commonly used chemicals in household products, including spray types. We identified the potential toxicity mechanism using human bronchial epithelial cells. After 6 h of exposure, DDAO decreased cell viability (non-apoptotic cell death) and formed numerous small artificial vacuoles in the cytoplasm. Cellular impedance decreased rapidly following exposure to DDAO, and condensation of the inner mitochondrial membrane, an increased level of cytochrome C, and a decrease in ATP production and mitochondrial volume were observed in DDAO-treated cells, affecting the level of second messengers. Impaired intracellular components, including lamellar bodies, were also found within the mitochondria or vacuoles. While the secretion of chemotactic cytokines decreased, the levels of IL-6, IL-11, MMP-1, and MMP-3 increased. Furthermore, DDAO enhanced the expression of the LAMP-2 protein and notably increased the volume of acidic compartments. More importantly, the expression of lipid metabolism-related genes was most affected following DDAO treatment. Considering that the volume of acidic compartments decreased rapidly at a concentration of 40 μg/mL, we suggest that DDAO may induce lysosomal-associated cell death (possible lipotoxicity) through structural damage to the cell (mitochondria) membrane, and that lysosomal membrane proteins may contribute to protecting cells from DDAO-induced impacts.