Metabolomics study on dibenz[a,h]anthracene exposure-induced pulmonary injury in rats after intratracheal instillation

Abstract Background Northern residents predominantly rely on coal-fired heating during winter, leading to severe air pollution. Polycyclic aromatic hydrocarbons (PAHs) adsorbed on atmospheric particulate matter pose significant health risks. Among PAHs, dibenz[a,h]anthracene (DahA), though present at lower environmental concentrations compared to other PAHs, exhibits a carcinogenic potency that is 10 or more times greater than benzo[a]pyrene (BaP), underscoring its potential harm. Despite reports on DahA's multiple toxic effects, its impact on metabolic networks remains poorly understood. Methods Based on the respiratory volume of adult rats and the concentration of PM2.5-bound DahA in heavily polluted cities of northern China, adult Sprague-Dawley rats were treated with DahA (0.07 μg/kg and 0.2 μg/kg) twice weekly for four weeks via intratracheal instillation. Metabolomic profiling of serum was performed using rapid resolution liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (RRLC/Q-TOF-MS) to elucidate metabolic disruptions caused by DahA exposure. Results DahA exposure induced significant oxidative stress and inflammatory responses in rats, accompanied by notable alterations in the serum metabolome. A total of 11 metabolites were found to be decreased, and 2 metabolites were increased, with disruptions observed in folate biosynthesis, glycerophospholipid metabolism, and nitrogen metabolism pathways. Additionally, metabolic dysregulation may interfere with the tricarboxylic acid cycle and compromise nucleotide homeostasis. Conclusion These findings enhance our understanding of the toxicological effects of DahA exposure and its role in lung damage. The results suggest that metabolic disturbances caused by DahA may contribute to the exacerbation of respiratory diseases associated with particulate matter-bound PAH pollution during the heating season in cold regions.