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Montelukast potentiates the protective effect of rofecoxib against kainic acid-induced cognitive dysfunction in rats.
MedLine Citation:
PMID:  22878042     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
There is an evolving consensus that mild cognitive impairment (MCI) serves as a prodrome to Alzheimer's disease. Antioxidants and COX-2 (cyclo-oxygenase-2) inhibitors have also been reported to have beneficial effects against conditions of memory impairment. Newer drugs like cysteinyl leukotriene inhibitors have shown neuroprotective effect in animal models of ischemia. Thus, the present study purports to explore the potential role of montelukast (a cysteinyl leukotriene inhibitor) in concert with rofecoxib (COX-2 inhibitor) and caffeic acid (a 5-LOX inhibitor and potent antioxidant) against kainic acid induced cognitive dysfunction in rats. In the experimental protocol, kainic acid (0.4μg/2μl) in artificial cerebrospinal fluid (ACSF) was given intrahippocampally (CA3 region) to induce a condition similar to MCI. Memory performance was measured on days 10-14 and the locomotor activity was measured on days 1, 7 and 14. For estimation of biochemical, mitochondrial and histopathological parameters, animals were sacrificed on day 14, stored at -80°C and the estimation was done on the 15th day. The treatment groups consisting of montelukast (0.5 and 1mg/kg), rofecoxib (5 and 10mg/kg) and caffeic acid (5 and 10mg/kg) showed significant improvement in memory performance, oxidative stress parameters and mitochondrial function as compared to that of control (kainic acid treated), however, combination of montelukast with rofecoxib showed significant improvement in their protective effect. Thus the present study emphasizes the positive modulation of cysteinyl leukotriene receptor inhibition on COX (cyclooxygenase) and LOX (lipoxygenase) pathways in the control of the neuroinflammation in kainic acid induced cognitive dysfunction in rats.
Authors:
Anil Kumar; Atish Prakash; Deeksha Pahwa; Jitendriya Mishra
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-3
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  -     ISSN:  1873-5177     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
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