Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicity in rat brain(1).
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.
Choudhary
S
S
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Gill
K D
KD
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004006:Dichlorvos / Q000633:toxicity*; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000209:etiology; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002135:Calcium-Binding Proteins; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D009553:Nimodipine; D004006:Dichlorvos; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002154:Calpain; D002118:Calcium