IBUPROFEN TREATMENT ENHANCES THE SURVIVAL OF MICE FOLLOWING EXPOSURE TO PHOSGENE

Abstract

The present study was designed to investigate the efficacy of ibuprofen (IBU) administered after a lethal dose of phosgene. Mice were exposed to 32 mg/m3 phosgene for 20 min and immediately injected with IBU (0, 3, 9, or 15 mg/mouse, ip). Five hours later, a second IBU injection was given but at half the original doses (0, 1.5, 4.5, and 7.5 mg/mouse). These are referred to throughout as the 0/0, 3/1.5, 9/4.5, and 15/7.5 mg IBU/mouse groups. Survival in these groups was determined at 12 and 24 h. In mice that died within 12 h, the lungs were removed, and lung wet weights, dry weights, wet/dry weight ratios, malondialdedyde (MDA), and nonprotein sulfhydryls (NPSH) were measured. Survival odds ratios were calculated for each dose at 12 and 24 h. The 12-h survival was 63% for 9/4.5 mg IBU and 82% for the 15/7.5 mg IBU group compared with 25% for saline-treated mice. At 24 h, survival rates were reduced to 19%, 19%, and 6%, respectively. In the 15/7.5 mg IBU group, dry weights, wet/dry weight ratios, and wet weights were significantly lower than in saline-treated mice at 12 h. MDA was lower only for the 9/4.5 mg IBU dose; however, NPSHs were greater across all IBU doses. The survival odds ratio was 5 for the 9/4.5 IBU group at 12 h and 13 for the 15/7.5 mg IBU group compared with 3.5 for both groups at 24 h. Therefore, IBU treatment increased the survival of mice at 12 h by reducing edema formation, lipid peroxidation, and glutathione depletion.