Citicoline (CDP-choline) protects myocardium from ischemia/reperfusion injury via inhibiting mitochondrial permeability transition

Aims: 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 Ca2+ accumulation cause ventricular arrhythmias and mitochondrial dysfunction. This occurs in consequence of increased nonspecific 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 CDPcholine may circumvent heart damage and mitochondrial permeability transition. Main 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 Ca2+ 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. Key findings: 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 Ca2+, an elevated value of transmembrane potential, and a high ratio of respiratory control. Furthermore, activity of cis-aconitase enzyme and mDNA structure were preserved. Significance: This work introduces COP-choline as a useful tool to preserve heart function from reperfusion damage by inhibiting mitochondrial permeability transition. (C) 2013 Elsevier Inc. All rights reserved.