Work

Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo

Year: 2025

Type: article

Abstract: Air pollution is indeed a pressing global public health issue that warrants comprehensive attention. Our research, conducted from 2015 to 2019, revealed significant air pollution in Guangzhou, with particularly high levels of NO 2 . Employing air-liquid interface incubation technique to develop in vitro models, we discovered that exposure to 10 ppm NO 2 could lead to cell death, oxidative stress, inflammation, and DNA damage. Concurrently, we utilized a dynamic oral-nasal inhalation exposure system to establish acute animal models, observing that short-term NO 2 exposure in mice resulted in pathological lung damage, oxidative stress, inflammation, and DNA damage. Mechanistically, transcriptome sequencing revealed an enrichment of ferroptosis in cells exposed to NO 2 . Mitochondrial damage, iron accumulation, and the differential expression of genes related to ferroptosis, as observed in both in vitro and in vivo studies, collectively suggest that ferroptosis contributed to NO 2 -induced toxicity. Furthermore, the silencing of STEAP3 , a gene significantly associated with ferroptosis, mitigated the effects of NO 2 exposure. Collectively, our findings indicated that elevated NO 2 levels in Guangzhou and NO 2 -induced toxicity may be linked to STEAP3 -mediated ferroptosis. This discovery is anticipated to offer novel perspectives on the hazards of NO 2 .

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.118353