Protective Effects of Aerosolized Scopolamine Against Soman-Induced Acute Respiratory Toxicity in Guinea Pigs

The protective efficacy of the antimuscarinic agent scopolamine was evaluated against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m3) by microinstillation inhalation exposure and treated 30 seconds la...

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Bibliographic Details
Published in:International journal of toxicology 2011-12, Vol.30 (6), p.639-649
Main Authors: Perkins, Michael W., Pierre, Zdenka, Rezk, Peter, Song, Jian, Oguntayo, Samuel, Morthole, Venee, Sciuto, Alfred M., Doctor, Bhupendra P., Nambiar, Madhusoodana P.
Format: Article
Language:English
Subjects:
Acetylcholinesterase - blood
Acetylcholinesterase - metabolism
Aerosols
Animals
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Butyrylcholinesterase - blood
Butyrylcholinesterase - metabolism
Cell Count
Chemical Warfare Agents - toxicity
Guinea Pigs
Lung - drug effects
Lung - metabolism
Lung - pathology
Male
Muscarinic Antagonists - pharmacology
Protective Agents - pharmacology
Respiratory Function Tests
Scopolamine Hydrobromide - pharmacology
Soman - toxicity
Trachea - drug effects
Trachea - pathology
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Summary:The protective efficacy of the antimuscarinic agent scopolamine was evaluated against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m3) by microinstillation inhalation exposure and treated 30 seconds later with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 hours. Treatment with scopolamine significantly increased survival and reduced clinical signs of toxicity and body weight loss in GD-exposed animals. Analysis of bronchoalveolar lavage (BAL) fluid showed normalization of GD-induced increased cell death, total cell count, and protein following scopolamine treatment. The BAL fluid acetylcholinesterase and butyrylcholinesterase levels were also increased by scopolamine treatment. Respiratory dynamics parameters were normalized at 4 and 24 hours post–GD exposure in scopolamine-treated animals. Lung histology showed that scopolamine treatment reduced bronchial epithelial and subepithelial inflammation and multifocal alveolar septal edema. These results suggest that aerosolized scopolamine considerably protects against GD-induced respiratory toxicity.
ISSN:1091-5818
1092-874X
DOI:10.1177/1091581811415874