Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicity in rat brain(1).

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 Ca(2+) with a concomitant increase in calpain activity. These increases in calpain activity and in the levels of intracellular Ca(2+) 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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Choudhary S,Gill KD

doi

10.1016/s0006-2952(01)00762-6

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

1265-72

issue

9

eissn

0006-2952

issn

1873-2968

pii

S0006295201007626

journal_volume

62

pub_type

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