BHA diet enhances the survival of mice exposed to phosgene: the effect of BHA on glutathione levels in the lung.
Phosgene-induced pulmonary edema formation has been under investigation for many years. One mechanism of protection may involve the use of antioxidants. Previously, it has been shown that butylated hydroxyanisole (BHA) treatment can enhance glutathione (GSH) levels. The present study focused on dietary supplementation in mice using BHA, a phenolic compound used in food preservation. Three groups of male CD-1 mice were studied: group 1, control animals fed with Purina rodent chow 5002; group 2, fed 0.75% BHA (w/w) in 5002; and group 3, fed 1.5% BHA (w/w) in 5002. Mice were fed for 22 days. On day 23 mice were exposed to 32 mg/m(3) phosgene for 20 min in a whole-body exposure chamber. Survival rate (SR) and odds ratio (OR) were determined at 12 and 24 h. In mice that died within 12 h, the lungs were removed immediately and lung wet weights (WW), dry weights (DW), lung wet weight/body weight ratio (LWW/BW), and lung tissue total glutathione (GSH) were assessed. For 12-h data, 6 mice from the 1.5% BHA group were sacrificed for lung tissue measurements. The SR for 0.75% BHA was 80% at 12 h and 55% at 24 h, compared with 36% and 23%, respectively, for controls. For 1.5% BHA, the 12- and 24-h SR were 100% and 92%, respectively. Odds ratios of 6.9 for 0.75% BHA and 46.6 for 1.5% BHA at 12 h and 4.0 and 42 for 0. 75% and 1.5% BHA, respectively, at 24 h were significantly (chi2) higher than control diet phosgene-exposed mice. Dietary pretreatment with 0.75% and 1.5% BHA significantly enhanced lung tissue GSH, 1.8-fold (p < or =.01) and 5.8-fold (p < or =.01), respectively, compared with phosgene-exposed control diet. Both BHA-supplemented diets significantly reduced WW. Only 1.5% BHA reduced DW, a measure of lung hyperaggregation. and LWW/BW compared with control diet. In air-exposed controls, BHA induced a dose-responsive decrease in WW, DW, LWW/BW ratio, and GSH. In conclusion, dietary pretreatment with BHA at the two dose levels reduced lung edema and lethality by enhancing lung tissue GSH in mice exposed to phosgene.
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Pharmacology Division, Neurotoxicology Branch, MCMR-UV-PN, U.S. Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Rd., Aberdeen Proving Ground, MD, 21010-5425, USA. alfred.sciuto@amedd.army.mil
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004032:Diet; D005978:Glutathione / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010705:Phosgene / Q000633:toxicity*
D000975:Antioxidants; D002619:Chemical Warfare Agents; D010705:Phosgene; D002083:Butylated Hydroxyanisole; D005978:Glutathione