Effect of dietary treatment with n-propyl gallate or vitamin E on the survival of mice exposed to phosgene

Authors

  • A. M. Sciuto,

    Corresponding author
    1. US Army Medical Research Institute of Chemical Defense, Pharmacology Division, Neurotoxicology Branch, Aberdeen Proving Ground, MD, USA
    • Pharmacology Division, Neurotoxicology Branch, MCMR-UV-PN, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010-5400, USA.
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  • T. S. Moran

    1. US Army Medical Research Institute of Chemical Defense, Pharmacology Division, Neurotoxicology Branch, Aberdeen Proving Ground, MD, USA
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  • This article is a U.S. government work and is in the public domain in the U.S.A.

Abstract

Phosgene, widely used in industrial processes, can cause life-threatening pulmonary edema and acute lung injury. One mechanism of protection against phosgene-induced lung injury may involve the use of antioxidants. The present study focused on dietary supplementation in mice using n-propyl gallate (nPG)—a gallate acid ester compound used infood preservation—and vitamin E. Five groups of male mice were studied: group 1, control-fed with Purina® rodent chow 5002; group 2, fed 0.75% nPG (w/w) in 5002; group 3, fed 1.5% nPG (w/w) in 5002; group 4 fed 1% (w/w) vitamin E in 5002; and group 5, fed 2% (w/w) vitamin E also in 5002. Mice were fed for 23 days. On day 23 mice were exposed to 32 mg m−3 (8 ppm) phosgene for 20 min (640 mg · min m−3) in a whole-body exposure chamber. Survival rates were determined at 12 and 24 h. In mice that died within 12 h, the lungs were removed and lung wet weights, dry weights, wet/dry weight ratios, lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and glutathione (GSH) were assessed. Vitamin E had no positive effect on any outcome measured. There was no significant difference between 1.5% nPG and any parameter measured or survival rate compared with 5002 + phosgene. However, dietary treatment with 0.75% nPG significantly increased survival rate (P ⩽ 0.002) and lowered TBARS (P ⩽ 0.05) compared with 5002 + phosgene at 12 h after exposure. Mice fed 0.75% nPG had a lower wet/dry wt ratio compared with those fed 1.5% nPG and a significantly increased lung tissue GSH 36%, compared with the 5002 + phosgene group. In conclusion, dietary treatment with a low level of the antioxidant nPG protected mice by decreasing lipid peroxidation and increasing lung tissue GSH. The higher level of nPG and both levels of vitamin E diets were ineffective, suggesting that a ceiling threshold level of antioxidants in lung tissue is required for survival against phosgene-induced lung injury. Published in 2001 by John Wiley & Sons, Ltd.

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