Inhalation exposure to sulfur mustard in the guinea pig model: clinical, biochemical and histopathological characterization of respiratory injuries.
Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt(50) and the inhaled LD(50) were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and few deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.
Allon
Nahum
N
Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel. nahuma@iibr.gov.il
Amir
Adina
A
Manisterski
Eliau
E
Rabinovitz
Ishay
I
Dachir
Shlomit
S
Kadar
Tamar
T
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D019570:Inhalation Exposure / Q000009:adverse effects*; D007928:Lethal Dose 50; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009151:Mustard Gas / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D017550:Spectroscopy, Fourier Transform Infrared
D000477:Alkylating Agents; D009151:Mustard Gas