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

Journal Article · Tue Sep 15 00:00:00 EDT 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.06.002· OSTI ID:21272650

Che, Magnus M ^[1]; Conti, Michele ^[2]; Chanda, Soma ^[1]; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter ^[2]; Amari, Ethery ^[1]; Sciuto, Alfred M ^[2]; Gordon, Richard K ^[3]; Doctor, Bhupendra P ^[1]; Nambiar, Madhusoodana P ^[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)

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.

• OSTI ID: 21272650
• Journal Information: Toxicology and Applied Pharmacology, Vol. 239, 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); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALKALINE PHOSPHATASE
ATROPINE
BIOLOGICAL MARKERS
BLOOD
BLOOD-BRAIN BARRIER
EDEMA
GUINEA PIGS
INHALATION
LUNGS
METABOLISM
METHYL BROMIDE
NOSE
TOXICITY