Posttreatment with ETYA protects against phosgene-induced lung injury by amplifying the glutathione to lipid peroxidation ratio.
Exposure to phosgene has been shown to cause severe and life-threatening pulmonary edema. There is evidence that successful treatment of phosgene-induced acute lung injury may be related to increased antioxidant activity. Acetylenic acids such as 5,8,11, 14-eicosatetraynoic acid (ETYA) have been shown to be effective in preventing pulmonary edema formation (PEF). In phosgene-exposed guinea pigs, we examined the effects of ETYA on PEF. Lipid peroxidation (thiobarbituric acid-reactive substance, TBARS) and total glutathione (GSH) were measured in lung tissue from isolated, buffer-perfused guinea pig lungs at 180 min after start of exposure. Guinea pigs were challenged with 175 mg/m(3) (44 ppm) phosgene for 10 min (1750 mg( small middle dot)min/m(3)). Five minutes after removal from the exposure chamber, guinea pigs were treated, ip, with 200 microl of 100 microM ETYA in ethanol (ETOH). Two hundred microliters of 50 microM ETYA in ETOH was added to the 200 ml perfusate every 40 min beginning at 60 min after start of exposure (t = 0). There were four groups in this study: air-exposed, phosgene-exposed, phosgene + ETYA-posttreated, and air + ETYA-posttreated. Posttreatment with ETYA prevented GSH depletion, 2. 7 +/- 0.5 micromol/mg protein versus 1 +/- 0.2 micromol/mg protein, for the untreated phosgene-exposed lungs (p < or =.05). ETYA posttreatment also significantly decreased PEF (p </=.025), as measured by lung wet weight/dry weight ratio, 16.1 +/- 2.5 versus 8.5 +/- 1 for phosgene-exposed + ETYA-posttreated guinea pigs. Postexposure treatment with ETYA significantly increased the GSH to TBARS protection ratio, 12 +/- 2, compared with the phosgene-exposed group, 3.7 +/- 0.5 (p < or =.05). In conclusion, ETYA posttreatment decreased PEF by increasing the GSH/TBARS protection ratio by functioning in an antioxidant-like capacity.
Sciuto
A M
AM
Pharmacology Division, Neurotoxicology Branch, MCMR-UV-PN, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA. alfred.sciuto@amedd.army.mil
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010705:Phosgene / Q000008:administration & dosage / Q000633:toxicity*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control*
D010705:Phosgene; D015117:5,8,11,14-Eicosatetraynoic Acid; D005978:Glutathione