Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

Journal Article · Tue Dec 01 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.006· OSTI ID:21344797

Allon, Nahum ^[1]; Amir, Adina; Manisterski, Eliau; Rabinovitz, Ishay; Dachir, Shlomit; Kadar, Tamar ^[1]

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1. Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100 (Israel)

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{sub 50} and the inhaled LD{sub 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.

• OSTI ID: 21344797
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.08.006; PII: S0041-008X(09)00335-4; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHEMICAL WARFARE AGENTS
EPITHELIUM
GLUTATHIONE
GUINEA PIGS
HEALING
INFLAMMATION
INFRARED SPECTRA
INHALATION
INJURIES
LUNGS
ORGANIC CHLORINE COMPOUNDS
ORGANIC SULFUR COMPOUNDS
SWELLING
TOXIC MATERIALS
TRACHEA
ANIMAL TISSUES
ANIMALS
BIOLOGICAL RECOVERY
BODY
DEFORMATION
DISEASES
DRUGS
HAZARDOUS MATERIALS
INTAKE
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
RESPONSE MODIFYING FACTORS
RODENTS
SPECTRA
SYMPTOMS
VERTEBRATES
WEAPONS