title: Citicoline (CDP-choline) protects myocardium from ischemia/reperfusion injury via inhibiting mitochondrial permeability transition.
abstract: OBJECTIVE
  Oxidative stress emerges after reperfusion of an organ following an ischemic period and results in tissue damage. In the heart, an amplified generation of reactive oxygen species and a significant Ca(2+) accumulation cause ventricular arrhythmias and mitochondrial dysfunction. This occurs in consequence of increased non-specific permeability. A number of works have shown that permeability transition is a common substrate that underlies the reperfusion-induced heart injury. The aim of this work was to explore the possibility that CDP-choline may circumvent heart damage and mitochondrial permeability transition.
  
  
  METHODS
  Rats were injected i.p. with CDP-choline at 20 mg/kg body weight. Heart electric behavior was followed during a closure/opening cycle of the left coronary descendent artery. Heart mitochondria were isolated from rats treated with CDP-choline, and their function was evaluated by analyzing Ca(2+) movements, achievement of a high level of the transmembrane potential, and respiratory control. Oxidative stress was estimated following the activity of the enzymes cis-aconitase and superoxide dismutase, as well as the disruption of mitochondrial DNA.
  
  
  RESULTS
  This study shows that CDP-choline avoided ventricular arrhythmias and drop of blood pressure. Results also show that mitochondria, isolated from CDP-choline-treated rats, maintained selective permeability, retained accumulated Ca(2+), an elevated value of transmembrane potential, and a high ratio of respiratory control. Furthermore, activity of cis-aconitase enzyme and mDNA structure were preserved.
  
  
  CONCLUSIONS
  This work introduces CDP-choline as a useful tool to preserve heart function from reperfusion damage by inhibiting mitochondrial permeability transition.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.affiliation: Departamento de Farmacología, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Unidad Coronaria, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: González-Pacheco
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Belmont
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, D. F. Mexico. Electronic address: echavez@salud.gob.mx.
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D003566:Cytidine Diphosphate Choline
keywords: CDP-choline; Heart reperfusion; Mitochondria; Oxidative stress; Permeability transition; Rat heart