Ozone Aggravated the Toxicity of Fine Particulate Matter by Impairing Membrane Stability and Facilitating Particle Internalization

The combined pollution of fine particulate matter (PM_2.5) and ozone (O₃) is increasing synergistically on a global scale, posing a serious threat to human health. However, the joint toxicity and the underlying mechanisms associated with co-exposure to PM_2.5 and O₃ remain poorly understood. Through complementary in vivo animal models and in vitro cellular assays, the results demonstrate that although there was no synergistic cytotoxicity effect between PM_2.5 and O₃, the presence of O₃ significantly enhanced the genotoxicity of PM_2.5 by inducing severe DNA double-strand breaks. Furthermore, O₃ exposure significantly exacerbated the bioaccumulation of PM_2.5 by disturbing the cellular membrane integrity, thus leading to synergistic toxicity in bronchial cells and mouse lungs. Astaxanthin (AST) effectively antagonized the adverse effects of PM_2.5 and O₃ co-exposure by maintaining cell membrane integrity. These findings enhance our understanding of the pathophysiological mechanisms induced by co-exposure to PM_2.5 and O₃, and provide a promising therapeutic strategy for treating respiratory diseases caused by unavoidable exposure to these pollutants.