Increased oxidative stress is associated with the development of organophosphate-induced delayed neuropathy

Hum Exp Toxicol. 2012 Dec;31(12):1214-27. doi: 10.1177/0960327112446842. Epub 2012 Jun 29.


Organophosphate-induced delayed neuropathy (OPIDN) is a progressive neuropathic disorder that manifests in days to weeks following exposure to an acute dose of organophosphates. The precise mechanism involved in the development of OPIDN is not clear as it develops after many days of the cessation of cholinergic crisis. The present study has been designed to understand the role of oxidative stress in the development of OPIDN, wherein neuropathy was developed by the administration of acute dose of monocrotophos (MCP) or dichlorvos (2,2-dichlorovinyl dimethyl phosphate (DDVP)) to rats. Significant motor deficits in terms of reduced spontaneous locomotor activity and performance on narrow beam test were observed after 14 days of exposure to MCP or DDVP, which persisted even on day 28, suggesting the development of OPIDN. Rats with OPIDN also exhibited an increase in malondialdehyde levels along with a decrease in thiol content in cerebral cortex, cerebellum and brain stem. Concomitantly, the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were reduced in the three brain regions. The biochemical and functional changes were associated with histological alterations in the brain regions studied. The results clearly indicate that the development of OPIDN is mediated in part through an increased oxidative stress and suggest that the strategies aimed at restoration of antioxidant capacity may be beneficial for the individuals with OPIDN-like symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / blood
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Death / drug effects
  • Dichlorvos / toxicity*
  • Exercise Test
  • Insecticides / toxicity*
  • Lipid Peroxidation / drug effects
  • Locomotion / drug effects
  • Male
  • Monocrotophos / toxicity*
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / pathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Oxidoreductases / metabolism
  • Postural Balance / drug effects
  • Rats
  • Rats, Wistar


  • Insecticides
  • Monocrotophos
  • Dichlorvos
  • Oxidoreductases
  • Acetylcholinesterase