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

Abstract

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.

• Authors: Harikesh Kalonia, Puneet Kumar, Anil Kumar
• Journal: Brain research (Brain Res) Vol. 1372 Pg. 115-26 (Feb 04 2011) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 21112316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Channel Blockers
• Cytokines
• Nitrites
• Verapamil
• Catalase
• Diltiazem
• Quinolinic Acid

Topics

• Analysis of Variance
• Animals
• Apoptosis (drug effects)
• Body Weight (drug effects)
• Calcium Channel Blockers (therapeutic use)
• Catalase (metabolism)
• Cytokines (metabolism)
• Diltiazem (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Enzyme-Linked Immunosorbent Assay (methods)
• Huntington Disease (chemically induced, drug therapy, physiopathology)
• Lipid Peroxidation (drug effects)
• Male
• Motor Activity (drug effects)
• Nitrites (metabolism)
• Psychomotor Performance (drug effects)
• Quinolinic Acid (toxicity)
• Rats
• Rats, Wistar
• Verapamil (therapeutic use)