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

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 NO2. Employing air-liquid interface incubation technique to develop in vit...

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Main Authors: Xiangyu Ding, Jiaying Xie, Sili Chen, Bingyun Zhang, Tao Zheng, Yitong Guo, Boheng Liang, Tongxing Shi, Qiaoyuan Yang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S014765132500689X
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author Xiangyu Ding
Jiaying Xie
Sili Chen
Bingyun Zhang
Tao Zheng
Yitong Guo
Boheng Liang
Tongxing Shi
Qiaoyuan Yang
author_facet Xiangyu Ding
Jiaying Xie
Sili Chen
Bingyun Zhang
Tao Zheng
Yitong Guo
Boheng Liang
Tongxing Shi
Qiaoyuan Yang
author_sort Xiangyu Ding
collection DOAJ
description 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 NO2. Employing air-liquid interface incubation technique to develop in vitro models, we discovered that exposure to 10 ppm NO2 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 NO2 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 NO2. 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 NO2-induced toxicity. Furthermore, the silencing of STEAP3, a gene significantly associated with ferroptosis, mitigated the effects of NO2 exposure. Collectively, our findings indicated that elevated NO2 levels in Guangzhou and NO2-induced toxicity may be linked to STEAP3-mediated ferroptosis. This discovery is anticipated to offer novel perspectives on the hazards of NO2.
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publisher Elsevier
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spelling doaj-art-56fb7d5c57f447fb8db8923ff92d453e2025-08-20T03:24:33ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0129911835310.1016/j.ecoenv.2025.118353Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivoXiangyu Ding0Jiaying Xie1Sili Chen2Bingyun Zhang3Tao Zheng4Yitong Guo5Boheng Liang6Tongxing Shi7Qiaoyuan Yang8Department of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, ChinaGuangzhou Center for Disease Control and Prevention, Guangzhou 510440, ChinaGuangzhou Center for Disease Control and Prevention, Guangzhou 510440, ChinaDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China; Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Correspondence to: Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao Town, Panyu District, Guangzhou 511436, China.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 NO2. Employing air-liquid interface incubation technique to develop in vitro models, we discovered that exposure to 10 ppm NO2 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 NO2 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 NO2. 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 NO2-induced toxicity. Furthermore, the silencing of STEAP3, a gene significantly associated with ferroptosis, mitigated the effects of NO2 exposure. Collectively, our findings indicated that elevated NO2 levels in Guangzhou and NO2-induced toxicity may be linked to STEAP3-mediated ferroptosis. This discovery is anticipated to offer novel perspectives on the hazards of NO2.http://www.sciencedirect.com/science/article/pii/S014765132500689XAir pollutionNO2Health effectsAir–liquid interface (ALI)Ferroptosis
spellingShingle Xiangyu Ding
Jiaying Xie
Sili Chen
Bingyun Zhang
Tao Zheng
Yitong Guo
Boheng Liang
Tongxing Shi
Qiaoyuan Yang
Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
Ecotoxicology and Environmental Safety
Air pollution
NO2
Health effects
Air–liquid interface (ALI)
Ferroptosis
title Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
title_full Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
title_fullStr Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
title_full_unstemmed Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
title_short Evaluation of atmospheric pollutant NO2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
title_sort evaluation of atmospheric pollutant no2 on respiratory toxicity associated with ferroptosis in vitro and in vivo
topic Air pollution
NO2
Health effects
Air–liquid interface (ALI)
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S014765132500689X
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