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

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.

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.

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.

This work introduces CDP-choline as a useful tool to preserve heart function from reperfusion damage by inhibiting mitochondrial permeability transition.