Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicity in rat brain

Sanjeev Choudhary, Kiran Dip Gill

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The effect of dichlorvos (200 mg/kg body weight) with or without nimodipine (6 mg/kg body weight/day for 3 days, starting 1 day prior to the administration of dichlorvos) on calcium homeostasis was studied in the rat brain. The delayed neurotoxic potential of dichlorvos was assessed in terms of neuropathy target esterase (NTE) inhibition in the brain and the subsequent development of motor incoordination at 21 days post-exposure. NTE activity had recovered up to 84% at the time of clinical manifestations. No signs of motor deficit were present when nimodipine was given with dichlorvos. The administration of dichlorvos alone caused an increase in intrasynaptosomal Ca2+ with a concomitant increase in calpain activity. These increases in calpain activity and in the levels of intracellular Ca2+ were not observed when nimodipine was administered to rats treated with dichlorvos. Also, the inhibition of calcium ATPase following the exposure to dichlorvos was reduced when animals received nimodipine. This indicates that nimodipine, a centrally acting calcium channel blocker, may contribute to the amelioration of dichlorvos-induced neurotoxicity by attenuation of calcium-mediated disruption of cytoskeletal homeostasis, without preventing NTE inhibition.

Original languageEnglish (US)
Pages (from-to)1265-1272
Number of pages8
JournalBiochemical Pharmacology
Volume62
Issue number9
DOIs
StatePublished - Nov 1 2001

Keywords

  • Calcium channel blocker
  • Calcium homeostasis
  • Dichlorvos
  • NTE
  • Nimodipine
  • OPIDN

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint Dive into the research topics of 'Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicity in rat brain'. Together they form a unique fingerprint.

Cite this