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oai:figshare.com:article/34018402 2026-09-28T20:11:34Z category_1 category_4 category_7 category_8 category_12 category_13 category_14 category_16 category_272 category_873 category_46 category_734 category_64 portal_63 item_type_6 month_year_09_2026

Pulmonary Injury, Functional Impairment, and Transcriptomic Responses Following Phosphine Inhalation in Mice: Implications for Therapeutic Development Esraa Mohamed (9768227) Andrea Adamcakova-Dodd (69390) Xuefang Jing (6002321) David K. Meyerholz (8468712) Mohammad Al-Natour (25133221) Peter S. Thorne (27275) Aliasger K. Salem (428760) Biophysics Biochemistry Medicine Microbiology Cell Biology Genetics Molecular Biology Physiology Environmental Sciences not elsewhere classified Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer therapeutic development phosphine scattered vessels filled promising therapeutic target potentially key element inducing injuries subsequent induce oxidative stress highly lethal gas chemical threat agent bulk rna sequencing bronchoalveolar lavage fluid accidentally released gas differentially expressed genes 1 protein complex human exposure occurs body exposure chamber total protein levels lungs showed foci 3 </ sub total protein junb </ jun </ protein synthesis genes involved following exposure widely used study examines significant increase significant decrease respiratory rate respiratory function ready accessibility pulmonary injury pulmonary effects platelet aggregates impacted pathways histopathological evaluation high lethality functional impairment exposed acutely dynamic whole containing pesticides cell death cell cycle cell counts available antidote atherosclerosis pathways 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. <i>Fos, Fosb, Jun</i>, and <i>Junb</i> 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. 2026-09-28T00:00:00Z Text Journal contribution 10.1021/acs.chemrestox.6c00223.s001 https://figshare.com/articles/journal_contribution/Pulmonary_Injury_Functional_Impairment_and_Transcriptomic_Responses_Following_Phosphine_Inhalation_in_Mice_Implications_for_Therapeutic_Development/34018402 CC BY-NC 4.0