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Title: Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

Abstract

We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar tomore » saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.« less

Authors:
 [1];  [2];  [1]; ; ;  [2];  [1];  [2];  [3];  [1];  [1]
  1. Department of Biochemical Pharmacology, Division of Biochemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500 (United States)
  2. Medical/Analytical Toxicology, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010 (United States)
  3. Department of Regulated Laboratories, Division of Regulated Activities, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500 (United States)
Publication Date:
OSTI Identifier:
21272650
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 239; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2009.06.002; PII: S0041-008X(09)00239-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKALINE PHOSPHATASE; ATROPINE; BIOLOGICAL MARKERS; BLOOD; BLOOD-BRAIN BARRIER; EDEMA; GUINEA PIGS; INHALATION; LUNGS; METABOLISM; METHYL BROMIDE; NOSE; TOXICITY

Citation Formats

Che, Magnus M, Conti, Michele, Chanda, Soma, Boylan, Megan, Sabnekar, Praveena, Rezk, Peter, Amari, Ethery, Sciuto, Alfred M, Gordon, Richard K, Doctor, Bhupendra P, Nambiar, Madhusoodana P, and Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs. United States: N. p., 2009. Web. doi:10.1016/j.taap.2009.06.002.
Che, Magnus M, Conti, Michele, Chanda, Soma, Boylan, Megan, Sabnekar, Praveena, Rezk, Peter, Amari, Ethery, Sciuto, Alfred M, Gordon, Richard K, Doctor, Bhupendra P, Nambiar, Madhusoodana P, & Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs. United States. https://doi.org/10.1016/j.taap.2009.06.002
Che, Magnus M, Conti, Michele, Chanda, Soma, Boylan, Megan, Sabnekar, Praveena, Rezk, Peter, Amari, Ethery, Sciuto, Alfred M, Gordon, Richard K, Doctor, Bhupendra P, Nambiar, Madhusoodana P, and Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. 2009. "Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs". United States. https://doi.org/10.1016/j.taap.2009.06.002.
@article{osti_21272650,
title = {Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs},
author = {Che, Magnus M and Conti, Michele and Chanda, Soma and Boylan, Megan and Sabnekar, Praveena and Rezk, Peter and Amari, Ethery and Sciuto, Alfred M and Gordon, Richard K and Doctor, Bhupendra P and Nambiar, Madhusoodana P and Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814},
abstractNote = {We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.},
doi = {10.1016/j.taap.2009.06.002},
url = {https://www.osti.gov/biblio/21272650}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 239,
place = {United States},
year = {Tue Sep 15 00:00:00 EDT 2009},
month = {Tue Sep 15 00:00:00 EDT 2009}
}