Journal article
Pulmonary Injury, Functional Impairment, and Transcriptomic Responses Following Phosphine Inhalation in Mice: Implications for Therapeutic Development
Chemical research in toxicology
09/28/2026
DOI: 10.1021/acs.chemrestox.6c00223
Abstract
Phosphine (PH3) is a highly lethal gas that is widely used as an agricultural fumigant. Human exposure occurs through inhalation of accidentally released gas or phosphide-containing pesticides. Its high lethality, combined with its ready accessibility, makes it a chemical threat agent. Although its toxic mechanism remains unclear, PH3 is known to induce oxidative stress, leading to cell death. With no available antidote, this study examines the pulmonary effects of acute PH3 inhalation exposure in order to support future treatment strategies and identifies key biological pathways affected in the lungs and hearts. Female mice were exposed acutely to one of three PH3 doses in a dynamic whole-body exposure chamber. Following exposure, respiratory function, total protein levels in bronchoalveolar lavage fluid (BALF), and lung pathology were evaluated. Bulk RNA sequencing of PH3-exposed lungs and hearts was performed, and differentially expressed genes (DEGs) in tissues from exposed versus nonexposed mice were analyzed. Animals exposed to high PH3 doses experienced a significant decrease in respiratory rate and had to be euthanized within 5 h postexposure. There was a significant increase in total protein and cell counts in BALF of PH3-exposed mice at the medium and high doses, and histopathological evaluation of lungs showed foci of hypercellularity and scattered vessels filled with platelet aggregates and neutrophils, indicative of early pulmonary thrombi formation. Gene expression analysis revealed upregulation of genes involved in protein synthesis, inflammation, cell cycle, and apoptosis. The MAPK, IL-17, and atherosclerosis pathways were among the most impacted pathways in lung and heart tissues. Fos, Fosb, Jun, and Junb were significantly upregulated following exposure; all of them are components of the AP-1 protein complex, a potentially key element in inducing injuries subsequent to PH3 exposure and therefore a promising therapeutic target.
Details
- Title: Subtitle
- Pulmonary Injury, Functional Impairment, and Transcriptomic Responses Following Phosphine Inhalation in Mice: Implications for Therapeutic Development
- Creators
- Esraa Mohamed - University of IowaAndrea Adamcakova-Dodd - University of IowaXuefang Jing - University of IowaDavid K. Meyerholz - University of IowaMohammad Al-Natour - University of IowaPeter S. Thorne - University of IowaAliasger K. Salem - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology
- DOI
- 10.1021/acs.chemrestox.6c00223
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Publisher
- American Chemical Society
- Grant note
- National Institute of Environmental Health Sciences: P30 ES005605 Environmental Health Sciences Research Center, University of Iowa: NA
This project was supported by NIH R21 ES032937 and the University of Iowa Environmental Health Sciences Research Center, NIH P30 ES005605. We acknowledge the support of the Comparative Pathology Core of the Precision Medicine Center for Cystic Fibrosis (NIH P30 DK054759) at the University of Iowa for providing technical and professional expertise.
- Language
- English
- Electronic publication date
- 09/28/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Occupational and Environmental Health; Research Administration; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9985240974402771
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