Document Detail


Xanthine oxidase contributes to mitochondrial ROS generation in an experimental model of cocaine-induced diastolic dysfunction.
MedLine Citation:
PMID:  22967988     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT: Recent studies have shown that long-term cocaine use induces diastolic impairment and a myocardial oxidative stress. Recently, we have reported that cocaine-induced cardiac dysfunction may be due to a mitochondrial reactive oxygen species (ROS) overproduction which occurs at the same time as xanthine oxidase (XO) activation. In this work, we hypothesized that XO activation contributes to mitochondrial ROS overproduction, which in turn contributes to diastolic dysfunction. To test this, we used a well-established in vivo model of cocaine-induced diastolic dysfunction. In this experimental model treated with or without allopurinol, an inhibitor of XO, we measured mitochondrial ROS production and function. Mitochondrial alterations were characterized by an increase in oxygen consumption through complexes I and III, a reduction in ATP production, and an increased ROS production specifically in isolated interfibrillar mitochondria. Allopurinol treatment prevented the rise in mitochondrial ROS levels and the decrease in ATP production. In the same way, allopurinol treatment improved ventricular relaxation with a decrease in Tau, an index of LV relaxation and of end-diastolic pressure volume relation. These results confirmed the critical role of xanthine oxidase in the sequence of events leading to cocaine-induced cardiac dysfunction.
Authors:
Aurélia Vergeade; Paul Mulder; Cathy Vendeville; Renée Ventura-Clapier; Christian Thuillez; Christelle Monteil
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-10
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  -     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
†Univ Rouen, INSERM U1096, Rouen, F-76183 France §Univ Paris-Sud 11, INSERM U769, Châtenay-Malabry F-92296 France ‡Univ Rouen, ABTE EA 4651, Rouen, F-76183 France.
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