Document Detail


Effect of combination of endothelin receptor antagonist (TAK-044) and aspirin in middle cerebral artery occlusion model of acute ischemic stroke in rats.
MedLine Citation:
PMID:  17609737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study was carried out to investigate the effect of the combination of an endothelin antagonist TAK-044 and an antiinflammatory agent aspirin in middle cerebral artery (MCA) occlusion model of acute ischemic stroke in rats. Male Wistar rats were pretreated with TAK-044 (5 mg/kg, i.p.) and aspirin (50 mg/kg, i.p.) for 7 days individually and in combination in different groups, and were thereafter subjected to focal ischemia for 2 h by occlusion of MCA using intraluminal thread. Twenty-four hours later, the rats were subjected to motor performance tests and killed subsequently for estimation of markers of oxidative stress malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD). The control group received the vehicle and the same protocol was followed. In vehicle-treated MCA occluded rats, significant (p < 0.01) motor impairment, with elevated levels of MDA (600.8 +/- 14.4 nmol/g tissue) and decreased levels of GSH (61.1 +/- 3.1 microg/g tissue) and SOD (8.5 +/- 0.5 U/mg protein,) was observed. Pretreatment with TAK-044 and aspirin for 7 days significantly improved motor function and attenuated the raised levels of MDA (475 +/- 14 and 538 +/- 17.3 nmol/g tissue, respectively) and the decrease in GSH (101 +/- 5 and 100 +/- 4.5 microg/g tissue, respectively) and SOD (12.1 +/- 0.5 and 10.5 +/- 0.6 U/mg protein, respectively), as compared to vehicle-treated MCA occluded rats. Combination of both the agents did not show a significant difference as compared to the individual drugs alone. The present study demonstrates that, although protection was observed with both the drugs (TAK-044 and aspirin), there was no enhanced effect when both agents were given in combination.
Authors:
S Briyal; A Gulati; Y K Gupta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Methods and findings in experimental and clinical pharmacology     Volume:  29     ISSN:  0379-0355     ISO Abbreviation:  Methods Find Exp Clin Pharmacol     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-07-04     Completed Date:  2007-10-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7909595     Medline TA:  Methods Find Exp Clin Pharmacol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  257-63     Citation Subset:  IM    
Copyright Information:
(c) 2007 Prous Science. All rights reserved.
Affiliation:
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*,  therapeutic use
Aspirin / pharmacology*,  therapeutic use
Brain Ischemia / complications*,  drug therapy,  etiology,  metabolism
Disease Models, Animal
Drug Therapy, Combination
Glutathione / metabolism
Infarction, Middle Cerebral Artery / complications*,  drug therapy,  metabolism
Male
Malondialdehyde / metabolism
Motor Activity / drug effects
Neuroprotective Agents / pharmacology*,  therapeutic use
Oxidative Stress / drug effects
Peptides, Cyclic / pharmacology*,  therapeutic use
Rats
Rats, Wistar
Receptors, Endothelin / antagonists & inhibitors*,  metabolism
Stroke / etiology,  metabolism,  prevention & control*
Superoxide Dismutase / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Neuroprotective Agents; 0/Peptides, Cyclic; 0/Receptors, Endothelin; 157380-72-8/TAK 044; 50-78-2/Aspirin; 542-78-9/Malondialdehyde; 70-18-8/Glutathione; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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