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In vitro Cell Culture Model for Toxic Inhaled Chemical Testing

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Ascorbate and deferoxamine administration after chlorine exposure decrease mortality and lung injury in mice.

Sotirios G Zarogiannis¹, Asta Jurkuvenaite, Solana Fernandez

¹Department of Anesthesiology, School of Medicine and Public Health, University of Alabama at Birmingham, 35294, USA.

American Journal of Respiratory Cell and Molecular Biology

|December 7, 2010

Summary

Antioxidants ascorbate and deferoxamine significantly reduced mortality and lung injury in mice exposed to chlorine gas. This treatment offers a potential therapeutic strategy for acute lung injury caused by chlorine inhalation.

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Area of Science:

Toxicology
Pulmonary Medicine
Pharmacology

Background:

Chlorine (Cl(2)) gas exposure is a significant occupational and environmental hazard.
Acute lung injury from chlorine gas inhalation currently lacks effective treatments.
Oxidative stress and inflammation play key roles in chlorine-induced lung damage.

Purpose of the Study:

To evaluate the efficacy of antioxidants, specifically ascorbate and deferoxamine, in mitigating mortality and lung injury following chlorine gas exposure.
To investigate the protective mechanisms of these antioxidants against chlorine-induced acute lung injury.

Main Methods:

C57BL/6 mice were exposed to 600 ppm of chlorine gas for 45 minutes.
Ascorbate and deferoxamine were administered via intramuscular injection and nose-only inhalation starting 1 hour post-exposure for 3 days.
Control groups received vehicle treatments (saline or water).
Outcomes assessed included mortality, bronchoalveolar lavage (BAL) fluid analysis (protein, cell counts, epithelial cells), and lipid peroxidation.

Main Results:

Mortality was reduced fourfold in the antioxidant treatment group compared to controls (22% vs. 78%, P = 0.007).
Surviving mice treated with antioxidants showed significantly lower protein concentrations, cell counts, and epithelial cells in BAL fluid.
Antioxidant treatment led to a threefold reduction in lipid peroxidation in BAL fluid.
Lung tissue ascorbate levels correlated inversely with BAL protein and inflammatory cell counts.

Conclusions:

Combined administration of ascorbate and deferoxamine effectively reduces mortality following chlorine gas exposure.
These antioxidants decrease lung injury by mitigating alveolar-capillary permeability, inflammation, epithelial cell damage, and lipid peroxidation.
This study highlights a promising therapeutic approach for acute lung injury induced by chlorine gas.