Document Detail

4'-Chlorodiazepam, a translocator protein (18 kDa) antagonist, improves cardiac functional recovery during postischemia reperfusion in rats.
MedLine Citation:
PMID:  20407080     Owner:  NLM     Status:  MEDLINE    
Inhibition of translocator protein (18 kDa) (TSPO) can effectively prevent reperfusion-induced arrhythmias and improve postischemic contractile performance. Mitochondrial permeability transition pore (mPTP) opening, mediated mainly through oxidative stress during ischemia/reperfusion (I/R), is a key event in reperfusion injury. 4'-Chlorodiazepam is a widely used TSPO antagonist. However, whether 4'-chlorodiazepam can improve cardiac functional recovery during postischemia reperfusion by affecting oxidative enzymes, reducing reactive oxygen species (ROS) and thereby inhibiting mPTP opening is still unknown. Cardiac function including heart rate, coronary flow rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal time derivatives of pressure (+/-dP/dt max) and the severity of ventricular arrhythmias were analyzed in isolated rat hearts during I/R. mPTP opening, ROS and oxidative enzyme activities were measured with fluorometric or spectrophotometric techniques. 4'-Chlorodiazepam did not affect heart rate and coronary flow rate, but abolished the increase in LVEDP, accelerated the recovery of LVDP and +/-dP/dt max, and reduced the severity of ventricular arrhythmias. The mPTP opening probability was reduced by 4'-chlorodiazepam, accompanied by a reduction in ROS level. In addition, the activities of mitochondrial electron transport chain complex I and complex III were increased, while those of xanthine oxidase and NADPH oxidase were reduced. Therefore, 4'-chlorodiazepam may improve cardiac functional recovery during reperfusion, potentially by affecting the activities of oxidative enzymes, reducing ROS and thereby inhibiting mPTP opening. The present study presents evidence that 4'-chlorodiazepam could be a novel adjunct to reperfusion.
Junjie Xiao; Dandan Liang; Hong Zhang; Ying Liu; Fajie Li; Yi-Han Chen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  235     ISSN:  1535-3699     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-04-28     Revised Date:  2010-07-29    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  England    
Other Details:
Languages:  eng     Pagination:  478-86     Citation Subset:  IM    
Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, China.
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MeSH Terms
Antilipemic Agents / pharmacology,  therapeutic use
Benzodiazepinones* / pharmacology,  therapeutic use
Carrier Proteins / antagonists & inhibitors*
Heart / drug effects*
Mitochondria, Heart / drug effects,  metabolism
Mitochondrial Membrane Transport Proteins / drug effects,  metabolism
Myocardial Reperfusion Injury* / drug therapy,  metabolism
Myocardium* / metabolism
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Receptors, GABA-A / antagonists & inhibitors*
Recovery of Function / drug effects*
Reg. No./Substance:
0/Antilipemic Agents; 0/Benzodiazepinones; 0/Carrier Proteins; 0/Mitochondrial Membrane Transport Proteins; 0/Reactive Oxygen Species; 0/Receptors, GABA-A; 0/mitochondrial permeability transition pore; 141440-82-6/Bzrp protein, rat; 14439-61-3/4'-chlorodiazepam

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