In vitro toxic synergistic effects of exogenous pollutants-trimethylamine and its metabolites on human respiratory tract cells

Abstract The wide presence of volatile organic amines in atmosphere has been clarified to relate to adverse effects on human respiratory health. However, toxic effects of them on human respiratory tract and their metabiotic mechanism of in vivo transformation have not been elucidated yet. Herein, cell viability and production of reactive oxygen species (ROSs) were first investigated during acute exposure of trimethylamine (TMA) to bronchial epithelial cells (16HBE), along with identification of toxic metabolites and metabolic mechanisms of TMA from headspace atmosphere and cell culture. Results showed that cell activity decreased and ROS production increased with raising exposure TMA concentration. Toxic effect may be induced not only by TMA itself, but also more likely by its cellular metabolites. Increased dimethylamine identified in headspace atmosphere and cell solution was the main metabolite of TMA, and methylamine was also confirmed to be a further metabolite. In addition, TMA can also be oxygenated to generate N,N-dimethylformamide and N,N'-Bis(2-hydroxyethyl)-1,2-ethanediaminium by N-formylation or hydroxylation, which was considered to be the participation of cytochrome P450 (CYP) enzymes. Overall, we can conclude that respiratory tract cells may produce more toxic metabolites during exposure of toxic organic amines, which together further induce cellular oxidative stress and necrosis. Hence, the environment and health impact of metabolites as well as original parent atmospheric organic amines should be paid more attention in further researches and disease risk assessments.