ArticleToxicological sciences : an official journal of the Society of Toxicology2015
NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Phosgene-Induced acute lung injury: Approaches for mechanism-based treatment strategies.Frontiers in immunology · 2022Pooled it
- Innovative myeloid ecotropic viral integration site 1-engineered exosome platform combating oxidative stress and inflammation in acute pulmonary damage.Bioengineering & translational medicine · 2026Article
- Sulforaphane attenuates phosgene-induced acute lung injury via the Nrf2-HO-1/NQO1 pathway.Journal of thoracic disease · 2024Article
- Metabolomics combined with network pharmacology reveals anti-asthmatic effects ofChinese herbal medicines · 2024Article
- Countermeasures against Pulmonary Threat Agents.The Journal of pharmacology and experimental therapeutics · 2024Review
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- Review of Inhalation Health Risks Involving Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) Used as Disinfectants in Household Humidifiers.Journal of Korean medical science · 2022Review
- Mechanism of Phosgene-Induced Acute Lung Injury and Treatment Strategy.International journal of molecular sciences · 2021Review
- Transient receptor potential channels in pulmonary chemical injuries and as countermeasure targets.Annals of the New York Academy of Sciences · 2020Article
- Disease-modifying treatment of chemical threat agent-induced acute lung injury.Annals of the New York Academy of Sciences · 2020Review
- Development of an acute, short-term exposure model for phosgene.Toxicology mechanisms and methods · 2019Article
- Phosgene inhalation causes hemolysis and acute lung injury.Toxicology letters · 2019Article
- Keratinocyte Growth Factor-2 Is Protective in Oleic Acid-Induced Acute Lung Injury in Rats.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.Military medicine · 2018Article
- Nitrite-induced acute kidney injury with secondary hyperparathyroidism: Case report and literature review.Medicine · 2018Review
- Phosgene-induced acute lung injury (ALI): differences from chlorine-induced ALI and attempts to translate toxicology to clinical medicine.Clinical and translational medicine · 2017Review
- An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness.Annals of the American Thoracic Society · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2 expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice, mediated partially through downregulation of surfactant protein B (SP-B) expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled phosgene produced increases in bronchoalveolar lavage fluid protein, histologic lung injury, and lung NOS-2 expression at 24 h. Administration of the selective NOS-2 inhibitor 1400 W via inhalation, but not via systemic delivery, significantly attenuated phosgene-induced ALI and preserved epithelial barrier integrity. Furthermore, aerosolized 1400 W augmented expression of SP-B and prevented downregulation of tight junction protein zonula occludens 1 (ZO-1), both critical for maintenance of normal lung physiology and barrier integrity. We also demonstrate for the first time that NOS-2-derived nitric oxide downregulates the ZO-1 expression at the transcriptional level in human lung epithelial cells, providing a novel target for ameliorating vascular leak in ALI. Our data demonstrate that lung NOS-2 plays a critical role in the development of phosgene-induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel therapeutic strategy for its treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.