Efficacy of ibuprofen and pentoxifylline in the treatment of phosgene-induced acute lung injury.
Phosgene, a highly reactive former warfare gas, is a deep lung irritant which produces adult respiratory distress syndrome (ARDS)-like symptoms following inhalation. Death caused by phosgene involves a latent, 6-24-h, fulminating non-cardiogenic pulmonary edema. The following dose-ranging study was designed to determine the efficacy of a non-steroidal anti-inflammatory drug, ibuprofen (IBU), and a methylxanthine, pentoxifylline (PTX). These drugs were tested singly and in combination to treat phosgene-induced acute lung injury in rats. Ibuprofen, in concentrations of 15-300 mg kg-1 (i.p.), was administered to rats 30 min before and 1 h after the start of whole-body exposure to phosgene (80 mg m-3 for 20 min). Pentoxifylline, 10-120 mg kg-1 (i.p.), was first administered 15 min prior to phosgene exposure and twice more at 45 and 105 min after the start of exposure. Five hours after phosgene inhalation, rats were euthanized, the lungs were removed and wet weight values were determined gravimetrically. Ibuprofen administered alone significantly decreased lung wet weight to body weight ratios compared with controls (P < or = 0.01) whereas PTX, at all doses tested alone, did not. In addition, the decrease in lung wet weight to body weight ratio observed with IBU+PTX could be attributed entirely to the dose of IBU employed. This is the first study to show that pre- and post-treatment with IBU can significantly reduce lung edema in rats exposed to phosgene.
Pathophysiology Division, United States Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010-5425, USA.
A M
AM
Sciuto
R R
RR
Stotts
H H
HH
Hurt
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002619:Chemical Warfare Agents / Q000633:toxicity; D004195:Disease Models, Animal; D004357:Drug Synergism; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010705:Phosgene / Q000008:administration & dosage / Q000633:toxicity; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002619:Chemical Warfare Agents; D010726:Phosphodiesterase Inhibitors; D010705:Phosgene; D010431:Pentoxifylline; D007052:Ibuprofen