Licofelone attenuates quinolinic acid induced Huntington like symptoms: possible behavioral, biochemical and cellular alterations.

Abstract

Cyclo-oxygenase and lipoxygenase enzymes are involved in arachidonic acid metabolism. Emerging evidence indicates that cyclo-oxygenase and lipoxygenase inhibitors prevent neurodegenerative processes and related complications. Therefore, the present study has been designed to explore the neuroprotective potential of licofelone (dual COX-2/5-LOX inhibitor) against quinolinic acid induced Huntington like symptom in rats. Intrastriatal administration of quinolinic acid significantly caused reduction in body weight and motor function (locomotor activity, rotarod performance and beam walk test), oxidative defense (as evidenced by increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidant enzymes), alteration in mitochondrial enzyme complex (I, II and IV) activities, raised TNF-α level and striatal lesion volume as compared to sham treated animals. Licofelone (2.5, 5 and 10 mg/kg) treatment significantly improved body weight, locomotor activity, rotarod performance, balance beam walk performance, oxidative defense, mitochondrial enzyme complex activities and attenuated TNF-α level and striatal lesion as compared to control (quinolinic acid). The present study highlights that licofelone attenuates behavioral, biochemical and cellular alterations against quinolinic acid induced neurotoxicity and this could be an important therapeutic avenue to ameliorate the Huntington like symptoms.

• Authors: Harikesh Kalonia, Puneet Kumar, Anil Kumar
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 35 Issue 2 Pg. 607-15 (Mar 30 2011) ISSN: 1878-4216 [Electronic] England
• PMID: 21237233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cyclooxygenase 2 Inhibitors
• Lipoxygenase Inhibitors
• Neuroprotective Agents
• Pyrroles
• Tumor Necrosis Factor-alpha
• Quinolinic Acid
• licofelone

Topics

• Animals
• Behavior, Animal (drug effects)
• Biochemical Phenomena (drug effects)
• Corpus Striatum (drug effects, physiopathology)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Huntington Disease (chemically induced, drug therapy, physiopathology)
• Lipid Peroxidation (drug effects)
• Lipoxygenase Inhibitors (pharmacology)
• Male
• Mitochondria (drug effects, enzymology, pathology)
• Motor Activity (drug effects)
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (metabolism, pathology, prevention & control)
• Oxidative Stress (drug effects)
• Pyrroles (pharmacology)
• Quinolinic Acid
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (metabolism)