Actions of Pyridostigmine and Organophosphate Agents on Chick Cells, Mice, and Chickens

Details

• Personal Author:
  Coatney EM ; Henderson JD ; Nieberg PS ; Spencer PS ; Wilson BW
• Description:
  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 [Description provided by NIOSH]
• Subjects:
  Animals Anti-Bacterial Agents Antibodies Chemistry Embryology Laboratories Nervous System Occupational Health Organophosphates Safety
• Keywords:
  Acetylcholinesterase Animal-studies Antibiotics Antibody-response Chemical-analysis Chemical-reactions Chemical-structure Chemical-synthesis Dose-response Embryopathology Embryotoxicity Exposure-levels Exposure-limits Laboratory-animals Nerve-damage Nerve-function Nerve-tissue Nerves Nervous-system Neuropathology Neuropathy Organo-phosphorus-compounds

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• ISSN:
  0148-0545
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; Oregon ; OSHA Region 10 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  131-139
• Volume:
  25
• Issue:
  2
• NIOSHTIC Number:
  nn:20033190
• Citation:
  Drug Chem Toxicol 2002 May; 25(2):131-139
• Contact Point Address:
  B. W. Wilson, University of California, Davis, California 95616
• Email:
  bwwilson@ucdavis.edu
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Start Date:
  19900930
• Source Full Name:
  Drug and Chemical Toxicology
• End Date:
  20020929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a5f846b541fb7cbd2d34a626f94c986076028c540151562f2fd1655d1f4a8c885f0efb656f9f18796c797819ac43467d44cb9ae6eff705c34b50a442a0430b8d
• Download URL:
  https://stacks.cdc.gov/view/cdc/188863/cdc_188863_DS1.pdf
• File Type:
  [PDF - 402.47 KB ]