Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats

Kalonia, Harikesh; Puneet Kumar,; Anil Kumar,

Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats

2011

Kalonia, Harikesh | Puneet Kumar, | Anil Kumar,

Huntington disease is a neurodegenerative disease with complex pathophysiology. Recently, role of neuroinflammation and interplay between various other cellular cascades have been suggested to be involved in pathophysiology of Huntington disease. Involvement of calcium overload mediated oxidative damage and excitotoxicity have been suggested to play a central role in quinolinic acid induced Huntington like symptoms. The present study has been carried out to investigate the neuroprotective effect of calcium channel blockers (verapamil and diltiazem) against quinolinic acid induced dysfunction in motor, biochemical and neuroinflammatory signaling in rats. Intrastriatal quinolinic acid administration leads to significant motor [locomotor (72% reduction), rotarod (55% reduction), balance beam walk performance] dysfunction coupled with the marked oxidative damage and increased neuroinflammatory markers [TNF-α (140%), IL-6 (115%), caspase-3(75%)] levels in striatum as compared to the sham treatment. Verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) drug treatment for 21days resulted in a significant improvement in the motor function (improvement in locomotor activity, rotarod and balance beam walk performance). Further, verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) treatment significantly attenuated oxidative damage, level of proinflammatory mediators (TNF-α IL-6 and caspase-3) in quinolinic acid treated animals. Results of the present study demonstrate that protective effect of these calcium channel blockers (verapamil, diltiazem) might be due to their inhibitory action on different neuroinflammatory pathways against quinolinic acid induced Huntington disease like symptoms in rats.

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AGROVOC Keywords

analysis of variance animal animals apoptosis apoptosis body weight brain calcium catalase cytokines drug therapy lipid peroxidation locomotion metabolism methods nitrites pathophysiology physiopathology rats rats rats toxicity verapamil verapamil

Bibliographic information

Published in

Brain research

Volume 1372 Pagination 115 - 126 ISSN 0006-8993

Publisher

Elsevier B.V.

Other Subjects

Drug effects; Chemically induced; Interleukin-6; Drug interactions; Neurodegenerative diseases; Huntington disease; Motor activity; Quinolinic acid; Disease models; Neuroprotective effect; Psychomotor performance; Caspase-3; Enzyme-linked immunosorbent assay; Placebos; Diltiazem; Therapeutic use; Dose-response relationship; Drug; Calcium channel blockers; Male; Wistar

Language

English

Type

Journal Article; Text

In AGRIS since: 2024-02-28

Format: MODS

Data Provider

This bibliographic record has been provided by National Agricultural Library

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Links

DOI http://dx.doi.org/10.1016/j.brainres.2010.11.060

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