Ozone induced pulmonary injury and respiratory dysfunction: Evidence, underlying mechanism and target investigation

Ground-level ozone (O₃) is a potent respiratory toxicant with accumulating data demonstrating respiratory harm in humans. However, its mechanistic impact on respiratory health and potential therapeutic target has not yet been fully illuminated. Here, we investigated the toxic mode of short-term ozone insult in mice lungs, excavated underlying mediators using integrated proteomic-metabolomic analysis, and assessed the interventive efficacy of taurine supplementation against ozone-elicited lung injury. Results showed that O₃ exposure dose-dependently impaired respiratory function and histology. Integrated proteomics and metabolomics analyses highlighted the crucial role of ferroptosis, cysteine and methionine metabolism, and alanine, aspartate and glutamate metabolism in O₃-eclited lung injury. Especially, ferroptosis was activated in the lungs of mice by O₃, as evidenced by the increased TFRC, ACSL4, and HO-1, and decreased FTH, FTL, and SLC7A11, indicating iron overload and lipid peroxidation. Ozone stimuli markedly reduced taurine and perturbed taurine and hypotaurine metabolism. More importantly, taurine supplementation could greatly improve respiratory health, including mitigating O₃-induced respiratory dysfunction, pulmonary histological damage, and inflammation, while inhibiting ferroptosis as its mediating effect. Taken together, the findings identify ferroptosis as a pivotal regulator linking O₃ exposure to lung injury and highlight the beneficial role of taurine in preventing O₃-induced respiratory deficits.