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Protection and inflammatory markers following exposure of guinea pigs to sarin vapour: comparative efficacy of three oximes
Author(s) -
Levy A.,
Chapman S.,
Cohen G.,
Raveh L.,
Rabinovitz I.,
Manistersky E.,
Kapon Y.,
Allon N.,
Gilat E.
Publication year - 2004
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1008
Subject(s) - sarin , pharmacology , nerve agent , chemistry , inhalation , bronchoalveolar lavage , medicine , anesthesia , acetylcholinesterase , biochemistry , lung , enzyme
The purpose of the present study was to compare the antidotal efcacy and the combined effects on inammatory markers of three oximes — toxogonine, TMB4 and 2‐PAM — in combination with anticholinergic drugs following exposure to sarin vapour by inhalation. Guinea pigs restrained in plethysmographs were exposed to various doses of sarin vapour (in the range of 1.4–4.4 ld 50 ). The antidotal mixture was injected immediately (5–20 s) following exposure (3 mg kg −1 atropine and 1 mg kg −1 benactyzine in combination with 6 mg kg −1 toxogonine, 2 mg kg −1 TMB4 or 12 mg kg −1 2‐PAM). Bronchoalveolar lavage (BAL) samples were taken from surviving animals 24 h after exposure to determine the levels of inammatory markers. A differential cell count was performed in BAL samples on Giemsa‐stained slides. The inammatory markers — histamine and prostaglandins (PGE) — were measured in BAL using radioimmunoassay (RIA) techniques. The survival rate in the various treatment groups and analysis of BAL samples showed that: (i) Toxogonine, TMB4 and 2‐PAM, without pyridostigmine pretreatment, at doses that were proportional to their doses in the respective auto‐injectors, exhibited similar antidotal efcacy against sarin exposure. (ii) The results demonstrated that a centrally acting anticholinergic drug is essential in the antidotal mixture to ensure survival. (iii) Histamine release and eosinophilia following sarin inhalation might require additional intervention, aimed at reducing the symptoms of allergic reaction and possibly expediting recovery. Copyright © 2004 John Wiley & Sons, Ltd.