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Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome
Sergey S Gutor1, Rodrigo I Salinas2, David S Nichols1
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
American Journal of Physiology. Lung Cellular and Molecular Physiology
|February 27, 2024
Summary
Repetitive sulfur dioxide (SO2) exposure in mice mimics post-deployment respiratory syndrome (PDRS) in soldiers, causing pulmonary vascular disease. Oxidative stress and isolevuglandins are key contributors, offering new therapeutic targets for veterans.
Area of Science:
- Environmental Health
- Pulmonary Medicine
- Toxicology
Background:
- Deployed soldiers exhibit higher respiratory symptoms, with some diagnosed with post-deployment respiratory syndrome (PDRS).
- Exposure to sulfur dioxide (SO2) is frequently reported by affected military personnel.
Purpose of the Study:
- To develop a mouse model of repetitive SO2 exposure that replicates PDRS.
- To investigate the mechanisms underlying SO2-induced pulmonary vascular pathology and disease.
Main Methods:
- Established a mouse model of repetitive SO2 exposure.
- Assessed lung pathology, pulmonary vascular remodeling, and mechanics.
- Investigated the role of oxidative stress, isolevuglandins (isoLGs), and Sirtuin-3 (Sirt3) in SO2-induced vascular changes.
- Evaluated the therapeutic potential of an isoLG scavenger (2-hydroxybenzylamine acetate, 2-HOBA) and Sirt3 modulation.
Main Results:
- Repetitive SO2 exposure induced PDRS-like features, including airway remodeling and pulmonary vascular (PV) disease.
- PV remodeling led to pulmonary hypertension and reduced exercise tolerance.
- SO2 exposure increased isoLG adducts and SOD2 acetylation; 2-HOBA treatment and Sirt3 overexpression attenuated PV remodeling.
Conclusions:
- Repetitive SO2 exposure recapitulates key aspects of PDRS in a mouse model.
- Oxidative stress, mediated by the ROS-isoLGs-Sirt3-SOD2 pathway, is a critical mechanism in SO2-induced PV remodeling.
- Findings provide insights into PDRS pathogenesis and suggest potential therapeutic strategies for affected veterans.
