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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Elsevier
2025-07-01
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| 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. |
| format | Article |
| id | doaj-art-56fb7d5c57f447fb8db8923ff92d453e |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| 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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