Document Detail


Suppression of myocardial ischemia-reperfusion injury by inhibitors of cytochrome P450 in rats.
MedLine Citation:
PMID:  19356728     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of inhibitors of cytochrome P450 on myocardial regional ischemia-reperfusion injury were examined in rats. Ischemia-reperfusion injury was evoked by ligation of the left anterior descending coronary artery for 1 h, followed by reperfusion for 24 h. Injuries were evident in causing infarction, decreases in left ventricular systolic pressure and left ventricle (dP/dt max)/P and an increase in left ventricular end-diastolic pressure. Increases in lipid peroxidation and reactive oxygen species levels in the ischemic region were observed. Intravenous injection of the potent cytochrome P450 inhibitor sulfaphenazole at 10 and 30 mg/kg at the time of reperfusion reduced infarct size by 41.7 and 73.2%, respectively; and improved cardiac function accompanied by the decrease in content of lipid peroxide and reactive oxygen species in the area at risk. Cardiac testosterone metabolism was inhibited by sulfaphenazole administration, indicating its inhibitory effects on cardiac cytochrome P450 activity. Another cytochrome P450 inhibitor, cimetidine, given intravenously, had similar effects to sulfaphenazole on reperfusion injury. Taken together, these results indicate that reactive oxygen species derived from cytochrome P450 play an important part in myocardial regional ischemia-reperfusion injury in vivo, and strongly support the hypothesis that cytochrome P450 inhibitors are promising therapeutic agents for cardiac ischemia-reperfusion injury.
Authors:
Yasuhiro Ishihara; Masaya Sekine; Mikio Nakazawa; Norio Shimamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-05
Journal Detail:
Title:  European journal of pharmacology     Volume:  611     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  64-71     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, Sanuki City, Kagawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects
Cimetidine / administration & dosage,  pharmacology*,  therapeutic use
Coronary Vessels / drug effects,  injuries,  metabolism
Cytochrome P-450 Enzyme System / antagonists & inhibitors*
Enzyme Inhibitors / administration & dosage,  pharmacology*,  therapeutic use
Heart / drug effects
Lipid Peroxidation / drug effects
Male
Myocardial Reperfusion Injury / drug therapy*,  metabolism,  pathology
Myocardium / metabolism,  pathology
Organ Size / drug effects
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Sulfaphenazole / administration & dosage,  pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 51481-61-9/Cimetidine; 526-08-9/Sulfaphenazole; 9035-51-2/Cytochrome P-450 Enzyme System

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