Interactive and delayed effects of pyridostigmine and physical stress on biochemical and histological changes in peripheral tissues of mice

J Appl Toxicol. 2000 Jul-Aug;20(4):327-34. doi: 10.1002/1099-1263(200007/08)20:4<327::aid-jat697>;2-j.


Gulf War veterans were taking pyridostigmine orally against possible exposure to nerve agents as well as being under physical stress. This study was designed to investigate the delayed effects of pyridostigmine and treadmill exercise on cholinesterase activity, lipid peroxidation and histology of peripheral tissues of mice. Male NIH Swiss mice were divided into four groups of 15 animals each and treated as follows: sedentary control; exercise training for 10 weeks; pyridostigmine (1.2 mg kg(-1), p.o.) for 2 weeks during weeks 5 and 6; and pyridostigmine plus exercise training. The mice were sacrificed 24 h after the last exercise, and blood, triceps muscle and sciatic nerve were isolated and analyzed. The group treated with pyridostigmine alone showed decreased plasma butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine plus exercise significantly decreased the BChE activity (79% of control), indicating an interactive effect of the combination. Acetylcholinesterase (AChE) activity did not alter significantly in red blood cells, platelets or sciatic nerve with either of the treatments. However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise. Creatine phosphokinase activity in plasma increased slightly (compared to control, pyridostigmine or exercise group) in mice treated with pyridostigmine plus exercise, which may be indicative of perturbation in the integrity of the skeletal muscle due to combination. However, there were no obvious histological abnormalities in the triceps muscle detected between experimental and control groups. Interaction of pyridostigmine and exercise significantly increased the concentration of the end product of lipid peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an oxidative stress response of the combination. These results indicate that physical stress enhanced the delayed toxic effects of a subchronic oral dose of pyridostigmine primarily in the skeletal muscle of mice.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism
  • Animals
  • Butyrylcholinesterase / drug effects
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / toxicity*
  • Creatine Kinase / drug effects
  • Creatine Kinase / metabolism
  • Delayed-Action Preparations
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Muscles / drug effects
  • Muscles / enzymology
  • Physical Conditioning, Animal / physiology
  • Pyridostigmine Bromide / toxicity*
  • Stress, Physiological / enzymology*
  • Stress, Physiological / metabolism


  • Cholinesterase Inhibitors
  • Delayed-Action Preparations
  • Creatine Kinase
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Pyridostigmine Bromide