Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart

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Title Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart
Author Venardos, Kylie; Harrison, Glenn; Headrick, John; Perkins, Anthony
Journal Name Clinical and Experimental Pharmacology and Physiology
Year Published 2004
Place of publication Australia
Publisher Blackwell Publishing Asia
Abstract 1. Auranofin, an antirheumatic gold compound, is an inhibitor of selenocysteine enzymes, such as thioredoxin reductase and glutathione peroxidase. These enzymes play an important role in protecting cardiac tissue from oxidative stress generated during ischaemia–reperfusion. 2. Auranofin (100 mg/kg) was administered to rats and their hearts were subjected to an in vitro model of ischaemia–reperfusion. The activity of thioredoxin reductase and glutathione peroxidase was determined in liver and heart tissues in an attempt to correlate enzymatic activity with heart recovery after ischaemia–reperfusion. 3. There was significantly less thioredoxin reductase activity in rat liver extracts, whereas the level of glutathione activity remained unchanged, demonstrating that the dose of auranofin used was able to selectively inhibit one of these enzyme systems. Rats administered auranofin displayed significantly impaired recovery from ischaemic insult. The end diastolic pressure was increased, whereas the rate pressure product was significantly decreased. 4. The level of postischaemic apoptosis was also assessed by examining caspase-3 activity in tissue homogenates. Auranofin significantly increased the degree of postischaemic apoptosis, leading to poor postischaemic recovery.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1111/j.1440-1681.2004.03993.x
Copyright Statement Copyright 2004 Blackwell Publishing. The definitive version is available at [www.blackwell-synergy.com.]
Volume 31
Issue Number 5-6
Page from 289
Page to 294
ISSN 0305-1870
Date Accessioned 2005-04-06
Date Available 2009-09-22T05:50:57Z
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Science & Technology
URI http://hdl.handle.net/10072/5662
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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