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Actions of pyridostigmine and organophosphate agents on chick cells, mice, and chickens.

Wilson-BW; Henderson-JD; Coatney-EM; Nieberg-PS; Spencer-PS

Drug Chem Toxicol 2002 May; 25(2):131-139

http://dx.doi.org/10.1081/DCT-120003255

20033190

Gulf War veterans were given pyridostigmine bromide (PB) tablets to enhance the therapeutic effect of antidotes to nerve agents in the event of exposure. The goal of this research is to examine whether combined exposure to PB and sarin (agent GB) is more neurotoxic to sensitive surrogate animals, mice and chickens, than if given separately. Scoping trials were performed to establish appropriate dose-response ranges for sarin and control chemicals. IC50 values were determined in chickens and mice for in vitro inhibition of acetylcholinesterase (AChE) and neuropathy target esterase (NTE). The results indicated PB neither inhibits NTE nor does it spare sarin's inhibition of AChE. Chick embryo nerve cells in vitro showed more inhibition of AChE activity and no faster recovery when PB treatment was followed by DFP treatment than the other way around. Experiments on chickens also indicated that PB treatment did not inhibit NTE and that it crossed the blood brain barrier inhibiting brain AChE although to a lesser extent than it inhibited blood cholinesterases. Other experiments determined multiple dose levels in chickens for sarin and DFP that inhibited > 80% of NTE, considered a threshold for triggering organophosphate-induced delayed neuropathy

Chemical-analysis; Chemical-reactions; Chemical-structure; Chemical-synthesis; Animal-studies; Animals; Organo-phosphorus-compounds; Nerve-damage; Nerve-function; Nerve-tissue; Nerves; Nervous-system; Neuropathology; Neuropathy; Exposure-levels; Exposure-limits; Dose-response; Antibiotics; Antibody-response; Acetylcholinesterase; Embryology; Embryopathology; Embryotoxicity; Laboratory-animals

B. W. Wilson, University of California, Davis, California 95616

DCTODJ

20020501

Journal Article

bwwilson@ucdavis.edu

1055222

Cooperative Agreement

2002

Cooperative-Agreement-Number-U07-CCU-906162

2

0148-0545

Drug and Chemical Toxicology

CA; OR