Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
Xiangyu Ding, Jiaying Xie, Sili Chen, Bingyun Zhang, Tao Zheng, Yitong Guo, Boheng Liang, Tongxing Shi, Qiaoyuan Yang
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 .