Acute Changes in Lung Histopathology and Bronchoalveolar Lavage Parameters in Mice Exposed to the Choking Agent Gas Phosgene

Abstract

Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonar y edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveola r lavage uid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m 3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to ltered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes. At 1,4,8,12,24, 48, and 72 hours after exposure each group of mice was euthanized and processed for histopatholog y, bronchoalveola r lavage or gravimetric measurements , respectively. Over time, the histopathologica l lesions were characterized by acute changes consisting of alveolar and interstitial edema, brin and hemorrhage , followed by signi cant alveolar and interstitial ooding with in ammatory cell in ltrates and scattered bronchiolar and terminal airway epithelial degeneratio n and necrosis. From 48 to 72 hours, there was partial resolution of the edema and degenerative changes, followed by epithelial and broblastic regeneration centered on the terminal bronchiolar areas. Bronchoalveola r lavage was processed for cell differential counts, LDH, and protein determination. Comparative analysis revealed signi cant increases in both postexposur e lung wet/dry weight ratios, and early elevations of BALF LDH and protein, and later elevations in leukocytes. This article describes the use of histopathology to chronicle the temporal pulmonary changes subsequent to whole body exposure to phosgene , and correlate these changes with BALF ingredients and postexposur e lung wet weights in an effort to characterize toxic gas-induced acute lung injury and identify early markers of phosgene exposure.

Dual Acute Proinflammatory and Antifibrotic Pulmonary Effects of Short Palate, Lung, and Nasal Epithelium Clone–1 after Exposure to Carbon Nanotubes

“…Our previously published proteomics data demonstrated the overexpression of SPLUNC1 in the lungs of mice after repeated exposures to SWCNTs (32), suggesting that the up-regulation of SPLUNC1 is a feature of the innate immune response to environmental foreign particles. In the present study, an 80-mg bolus of SWCNTs per mouse was delivered by pharyngeal aspiration to the mice.…”

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).…”

Clinical Drug Treatment of Edemagenic Gas-Induced Lung Injury

“…Because of its insoluble nature, phosgene attacks the deeper regions of the lung where it can alter the GSH redox enzymes (42). Furthermore, phosgene has been shown to increase lipid peroxidation, cause the release of sulfidopeptide leukotrienes, alter important cell ultrastructures, and react directly with lung surfactant (22,24,27,43). In addition, it has been shown that phosgene can form adducts with renal microsomal phospholipid polar heads (19).…”