Document Detail

Persistent/delayed toxic effects of low-dose sarin and pyridostigmine under physical stress (exercise) in mice.
MedLine Citation:
PMID:  15521554     Owner:  NLM     Status:  MEDLINE    
Pyridostigmine bromide, a reversible anticholinesterase drug, was used by military personnel during the Gulf War. They were under physical stress and might have been exposed to low-dose nerve gas, sarin. This study examined the interactions of low-dose sarin and pyridostigmine in exercised mice. Male NIH Swiss mice were treated as follows: 1) Control; 2) Sarin (0.01 mg/kg, sc); 3) exercise; 4) sarin plus exercise; 5) pyridostigmine; 6) pyridostigmine plus exercise; 7) pyridostigmine plus sarin; 8) pyridostigmine plus sarin plus exercise. Exercise was given daily for 10 weeks on treadmill and pyridostigmine and sarin were administered daily during the 5th and 6th weeks only. Respiratory exchange ratio decreased significantly during the dosing period of 5th and 6th weeks in groups 4, 6, and 8. Animals were sacrificed 24 hours after the ten-week exercise, tissues isolated and analyzed. Sarin significantly decreased butyrylcholine esterase (BChE) activity in plasma; AChE activity in platelet, triceps muscle, and striatum; neurotoxic esterase (NTE) activity in platelets, spinal cord, cortex and striatum and malondialdehyde (MDA) levels in sciatic nerve and cord. Sarin plus exercise significantly reduced BChE activity in plasma; acetylcholinesterase (AChE) activity in platelets, muscle, nerve and striatum; NTE activity in platelets, cord, cortex and striatum; and increased creatinine phosphokinase (CK) activity in plasma and MDA levels in cord. Pyridostigmine plus exercise significantly decrease BChE activity in plasma; AChE activity in muscle and enhanced malondialdehyde (MDA) levels in muscle. Pyridostigmine plus sarin significantly decreased NTE activity in platelets, cord, cortex and striatum. Pyridostigmine plus sarin plus exercise significantly altered AChE activity and MDA levels in muscle; and NTE activity in platelets, nerve, cord and cortex. Exercise significantly augmented the changes in plasma CK activity, muscle and nerve AChE activity, platelet NTE activity and cord MDA levels induced by sarin. It is concluded that physical stress (exercise) enhanced the persistent/delayed toxic effects of low-dose sarin and pyridostigmine in specific tissues of mice.
Kazim Husain; Satu M Somani
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Indian journal of physiology and pharmacology     Volume:  48     ISSN:  0019-5499     ISO Abbreviation:  Indian J. Physiol. Pharmacol.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-11-03     Completed Date:  2005-02-25     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0374707     Medline TA:  Indian J Physiol Pharmacol     Country:  India    
Other Details:
Languages:  eng     Pagination:  150-64     Citation Subset:  IM    
Departments of Surgery and Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794-9629, USA.
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MeSH Terms
Lipid Peroxidation / drug effects,  physiology
Physical Exertion / drug effects,  physiology*
Pyridostigmine Bromide / administration & dosage,  toxicity*
Sarin / administration & dosage,  toxicity*
Stress, Physiological / metabolism*
Time Factors
Reg. No./Substance:
101-26-8/Pyridostigmine Bromide; 107-44-8/Sarin

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