Document Detail


Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.
MedLine Citation:
PMID:  19684190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening. Isolated perfused rat hearts were subjected to global ischemia and reperfusion in the presence or absence of melatonin in a Langerdoff apparatus. Melatonin treatment significantly improves the functional recovery of Langerdoff hearts on reperfusion, reduces the infarct size, and decreases necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria isolated from melatonin-treated hearts are less sensitive than mitochondria from reperfused hearts to MPTP opening as demonstrated by their higher resistance to Ca(2+). Similar results were obtained following treatment of ischemic-reperfused rat heart with cyclosporine A, a known inhibitor of MPTP opening. In addition, melatonin prevents mitochondrial NAD(+) release and mitochondrial cytochrome c release and, as previously shown, cardiolipin oxidation associated with ischemia-reperfusion. Together, these results demonstrate that melatonin protects heart from reperfusion injury by inhibiting MPTP opening, probably via prevention of cardiolipin peroxidation.
Authors:
Giuseppe Petrosillo; Giuseppe Colantuono; Nicola Moro; Francesca M Ruggiero; Edy Tiravanti; Nicola Di Venosa; Tommaso Fiore; Giuseppe Paradies
Publication Detail:
Type:  In Vitro; Journal Article     Date:  2009-08-14
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  297     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-25     Completed Date:  2009-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1487-93     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics, Section of Anaesthesia, University of Bari, Bari, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*
Calcium / metabolism
Cardiolipins / metabolism
Cardiovascular Agents / pharmacology*
Cyclosporine / pharmacology
Cytochromes c / metabolism
Heart Rate / drug effects
L-Lactate Dehydrogenase / metabolism
Lipid Peroxidation / drug effects
Male
Melatonin / pharmacology*
Membrane Potential, Mitochondrial / drug effects
Mitochondria, Heart / drug effects*,  metabolism
Mitochondrial Membrane Transport Proteins / antagonists & inhibitors*,  metabolism
Myocardial Infarction / metabolism,  pathology,  physiopathology,  prevention & control*
Myocardial Reperfusion Injury / metabolism,  pathology,  physiopathology,  prevention & control*
Myocardium / metabolism*,  pathology
NAD / metabolism
Necrosis
Perfusion
Rats
Rats, Wistar
Recovery of Function
Time Factors
Ventricular Function, Left / drug effects
Ventricular Pressure / drug effects
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cardiolipins; 0/Cardiovascular Agents; 0/Mitochondrial Membrane Transport Proteins; 0/mitochondrial permeability transition pore; 53-84-9/NAD; 59865-13-3/Cyclosporine; 73-31-4/Melatonin; 7440-70-2/Calcium; 9007-43-6/Cytochromes c; EC 1.1.1.27/L-Lactate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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