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

Citation
S. Choudhary et Kd. Gill, Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicity in rat brain, BIOCH PHARM, 62(9), 2001, pp. 1265-1272
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
9
Year of publication
2001
Pages
1265 - 1272
Database
ISI
SICI code
0006-2952(20011101)62:9<1265:PEONOD>2.0.ZU;2-B
Abstract
The effect of dichlorvos (200 mg/kg body weight) with or without nimodipine (6 mg/kg body weight/day for 3 days, starting I day prior to the administr ation of dichlorvos) on calcium homeostasis was studied in the rat brain. T he delayed neurotoxic potential of dichlorvos was assessed in terms of neur opathy target esterase (NTE) inhibition in the brain and the subsequent dev elopment of motor incoordination at 21 days post-exposure. NTE activity had recovered up to 84% at the time of clinical manifestations. No signs of mo tor deficit were present when nimodipine was given with dichlorvos. The adm inistration of dichlorvos alone caused an increase in intrasynaptosomal Ca2 (+) with a concomitant increase in calpain activity. These increases in cal pain activity and in the levels of intracellular Ca2(+) were not observed w hen nimodipine was administered to rats treated with dichlorvos. Also, the inhibition of calcium ATPase following the exposure to dichlorvos was reduc ed when animals received nimodipine. This indicates that nimodipine, a cent rally acting calcium channel blocker, may contribute to the amelioration of dichlorvos-induced neurotoxicity by attenuation of calcium-mediated disrup tion of cytoskeletal homeostasis, without preventing NTE inhibition. (C) 20 01 Elsevier Science Inc. All rights reserved.