Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits.
We examined the effects of treatment with N-acetylcysteine (NAC) on pulmonary edema formation in isolated perfused rabbit lungs following in vivo phosgene exposure. This study focused on posttreatment intratracheal administration of NAC after exposure. Rabbits, 2 to 3 kg, were exposed to a cumulative dose of phosgene to attain a concentration x time exposure effect of 1,500 ppm/min. Lungs were perfused with Krebs-Henseleit buffer at 40 ml/min from 70 to 150 min after exposure. Pulmonary artery pressure (Ppa), tracheal pressure (Pt), and the rate of lung weight gain (LWG) were measured continuously. Perfusate concentration of peptide leukotrienes LTC4, D4, and E4 were measured every 20 min during perfusion. At the conclusion of the experiment, lung tissue was analyzed for reduced and oxidized glutathione (GSH and GSSG) and lipid peroxidation (thiobarbituric acid-reactive substances, TBARS). Exposure to phosgene significantly increased Pt, LWG, LTC4, D4, and E4, TBARS, and GSSG over time compared with controls. Compared with phosgene, intratracheal NAC lowered Ppa, LWG, LTC4, D4, and E4, TBARS, and GSSG. We conclude that NAC protected against phosgene-induced lung injury by acting as an antioxidant by maintaining protective levels of glutathione, reducing both lipid peroxidation and production of arachidonic acid metabolites.
Sciuto
A M
AM
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland.
Strickland
P T
PT
Kennedy
T P
TP
Gurtner
G H
GH
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010705:Phosgene / Q000506:poisoning*; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000517:prevention & control*; D011817:Rabbits; D013997:Time Factors
D000975:Antioxidants; D015289:Leukotrienes; D010705:Phosgene; D005978:Glutathione; D000111:Acetylcysteine