title: Protective effects of aerosolized scopolamine against soman-induced acute respiratory toxicity in guinea pigs.
abstract: 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/m(3)) 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.
authors.affiliation: Medical/Analytical Toxicology, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pierre
authors.forename: Peter
authors.initials: P
authors.lastname: Rezk
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Samuel
authors.initials: S
authors.lastname: Oguntayo
authors.forename: Venee
authors.initials: V
authors.lastname: Morthole
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D002452:Cell Count; D002619:Chemical Warfare Agents / Q000633:toxicity*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D012129:Respiratory Function Tests; D012601:Scopolamine / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects / Q000473:pathology
chemical_list: D000336:Aerosols; D002619:Chemical Warfare Agents; D018727:Muscarinic Antagonists; D020011:Protective Agents; D012999:Soman; D012601:Scopolamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase