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/m 3 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.

Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione

“…research on countermeasures to mitigate phosgene-induced ALI in controlled animal models has been published (Sciuto et al, 1995(Sciuto et al, , 1996Sciuto, 1997;Duniho et al, 2002;Sciuto and Hurt, 2004).…”

Posttreatment With Etya Protects Against Phosgene-Induced Lung Injury by Amplifying the Glutathione to Lipid Peroxidation Ratio

“…However, several promising compounds have been investigated. While many of these can work as pretreatments, others can reduce or ameliorate phosgene-induced pulmonary edema formation when administered after exposure (Sciuto, 1997;Sciuto et al, 1995Sciuto et al, , 1997. This has important clinical implications because in real-life situations individuals exposed to phosgene or other similarly acting toxic gases will be treated after exposure.…”

“…It is well known that lipid peroxidation is partly responsible for cellular and eventually tissue death. However, the presence of lipid peroxidative compounds may be sufficient for the continuance of the injury process, but in itself may not be necessary for cell death (Sciuto, 1997). The combination of increased GSH and decreased TBARS formation in the presence of ETYA may be suggestive that ETYA has some capacity to influence the course of injury.…”

Temporal Changes in Respiratory Dynamics in Mice Exposed to Phosgene

“…We have shown that as time increases there is a significant reduction in macrophages and increase in neutrophils in the lavage fluid of mice (Duniho et al, 2001). We have investigated the use of ibuprofen in three different animal models and found that ibuprofen not only reduced the lung wet/dry weight ratio, but also increased survival rates in mice when treatment occurred after exposure (Kennedy et al, 1990;Sciuto et al, 1996b;Sciuto, 1997). The delivery of these agents to exposed individuals should be through inhalation.…”