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 irritan t which produces adult respiratory distress syndrome (ARDS)-like sympt oms following inhalation. Death caused by phosgene involves a latent, 6-24-h, fulminating non-cardiogenic pulmonary edema. The following dos e-ranging study was designed to determine the efficacy of a non-steroi dal anti-inflammatory drug, ibuprofen (IBU), and a methylxanthine, pen toxifylline (PTX). These drugs were tested singly and in combination t o treat phosgene-induced acute lung injury in rats. Ibuprofen, in conc entrations 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 fi rst administered 15 min prior to phosgene exposure and twice more at 4 5 and 105 min after the start of exposure. Five hours after phosgene i nhalation, 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 less than or equal to 0.01) whereas PTX, at all dose s tested alone, did not. In addition, the decrease in lung wet weight to body weight ratio observed with IBU+PTX could be attributed entirel y to the dose of TSU employed. This is the first study to show that pr e- and post-treatment with IBU can significantly reduce lung edema in rats exposed to phosgene.