title: Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.
abstract: Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano N°1, Col Sección XVI, CP 14080 Tlalpan D.F. México.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.forename: Héctor
authors.initials: H
authors.lastname: González-Pacheco
authors.forename: Javier
authors.initials: J
authors.lastname: Belmont
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014284:Triiodothyronine / Q000009:adverse effects
chemical_list: D002316:Cardiotonic Agents; D004272:DNA, Mitochondrial; D014284:Triiodothyronine; D003566:Cytidine Diphosphate Choline; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D002118:Calcium
keywords: citicoline; cœur; heart; hyperthyroidism; hyperthyroïdie; mitochondria; mitochondrie; oxidative stress; stress oxydant