Oxidant Stress and Damage in Post-Ischemic Mouse Hearts: Effects of Adenosine

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Title Oxidant Stress and Damage in Post-Ischemic Mouse Hearts: Effects of Adenosine
Author Hack, Benjamin Daniel Noel; Witting, Paul K; Rayner, Benjamin S.; Stocker, Roland; Headrick, John Patrick
Journal Name Molecular and Cellular Biochemistry
Editor Naranjan S Dhalla
Year Published 2006
Place of publication Berlin, Germany
Publisher Springer Science + Business Media
Abstract Despite the general understanding that ischemia-reperfusion (I/R) promotes oxidant stress, specific contributions of oxidant stress or damage to myocardial I/R injury remain poorly defined. Moreover, whether endogenous 'cardioprotectants' such as adenosine act via limiting this oxidant injury is unclear. Herein we characterized effects of 20 min ischemia and 45 min reperfusion on cardiovascular function, oxidative stress and damage in isolated perfused mouse hearts (with glucose or pyruvate as substrate), and examined whether 10 ¼M adenosine modified these processes. In glucose-perfused hearts post-ischemic contractile function was markedly impaired (< 50% of pre-ischemia), cell damage assessed by lactate dehydrogenase (LDH) release was increased (12 ± 2 IU/g vs. 0.2 ± 0.1 IU/g in normoxic hearts), endothelial-dependent dilation in response to ADP was impaired while endothelial-independent dilation in response to nitroprusside was unaltered. Myocardial oxidative stress increased significantly, based on decreased glutathione redox status ([GSSG]/[GSG + GSSH] = 7.8 ± 0.3% vs. 1.3 ± 0.1% in normoxic hearts). Tissue cholesterol, native cholesteryl esters (CE) and the lipid-soluble antioxidant ±-tocopherol (±-TOH, the most biologically active form of vitamin E) were unaffected by I/R, whereas markers of primary lipid peroxidation (CE-derived lipid hydroperoxides and hydroxides; CE-O(O)H) increased significantly (14 ± 2 vs. 2 ± 1 pmol/mg in normoxic hearts). Myocardial ± -tocopherylquinone (±-TQ; an oxidation product of ± -TOH) also increased (10.3 ± 1.0 vs. 1.7 ± 0.2 pmol/mg in normoxic hearts). Adenosine treatment improved functional recovery and vascular function, and limited LDH efflux. These effects were associated with an anti-oxidant effect of adenosine, as judged by inhibition of I/R-mediated changes in glutathione redox status (by 60%), ±-TQ (80%) and CE-O(O)H (100%). Provision of 10 mM pyruvate as sole substrate (to by-pass glycolysis) modestly reduced I/R injury and changes in glutathione redox status and ±-TQ, but not CE-O(O)H. Adenosine exerted further protection and anti-oxidant actions in these hearts. Functional recoveries and LDH efflux correlated inversely with oxidative stress and ± -TQ (but not CE-O(O)H) levels. Collectively, our data reveal selective oxidative events in post-ischemic murine hearts, which are effectively limited by adenosine (independent of substrate). Correlation of post-ischemic cardiovascular outcomes with specific oxidative events (glutathione redox state, ±-TQ) supports an important anti-oxidant component to adenosinergic protection.
Peer Reviewed Yes
Published Yes
Volume 287
Issue Number 1-2
Edition 2006
Page from 165
Page to 175
ISSN 0300-8177
Date Accessioned 2006-07-02
Date Available 2007-08-07T04:47:32Z
Language en_AU
Research Centre Heart Foundation Research Centre; Griffith Health Institute
Faculty Griffith Health Faculty
Subject Medical Biochemistry: Other; Systems Physiology
URI http://hdl.handle.net/10072/14272
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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