POSTTREATMENT WITH ETYA PROTECTS AGAINST PHOSGENE-INDUCED LUNG INJURY BY AMPLIFYING THE GLUTATHIONE TO LIPID PEROXIDATION RATIO

Abstract

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/m³ (44 ppm) phosgene for 10 min (1750 mg min/m³). Five minutes after removal from the exposure chamber, guinea pigs were treated, ip, with 200 mu l of 100 mu M ETYA in ethanol (ETOH). Two hundred microliters of 50 mu M 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 mu mol/mg protein versus 1 +/- 0.2 mu mol/mg protein, for the untreated phosgene-exposed lungs (p less than or equal to.05). ETYA posttreatment also significantly decreased PEF (p less than or equal to.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 less than or equal to.05). In conclusion, ETYA posttreatment decreased PEF by increasing the GSH/TBARS protection ratio by functioning in an antioxidant-like capacity.