It has previously been demonstrated that phosphatidylinositol-3-kinase (PI3K)/Akt and cleaved
caspase-3 serve critical roles in the apoptosis of cardiac myocytes following
ischemia/reperfusion injury.
Epigallocatechin-3-gallate (EGCG), the predominant
catechin component of
green tea, has been reported to have potential cardioprotective effects in primary cultures of cardiac myocytes exposed to I/R injury, mediated through inhibition of signal transducers and activators of transcription-1 activity. In addition, it is also known that the
biological behavior of EGCG may be influenced by
metal ions, for example the hepatoprotective activity of EGCG has been reported to be enhanced by
zinc. In the present study, the protective effects of EGCG with
zinc were assessed on cultures of rat cardiac myoblasts exposed to
hypoxia/reoxygenation (H/R) injury. H9c2 cells were subjected to 3-h
hypoxia, followed by 1-h reperfusion. EGCG and/or
zinc were perfused prior to induced hypoxic stress. It was demonstrated that when EGCG interacted with
zinc, the anti-apoptotic activity was significantly enhanced. To the best of our knowledge, the current study was the first to demonstrate that EGCG + Zn(2+) protects H9c2 cells against H/R injury through activation of the PI3K/Akt pathway, as determined by western blotting. Since EGCG + Zn(2+) may, at least in part, protect cardiac myocytes against H/R-induced apoptotic cell death, the PI3K/Akt pathway of EGCG may be enhanced by its interactions with
zinc during H/R injury. Furthermore, it was suggested that a similar procedure may be implemented in a clinical setting, in order to maximize PI3K/Akt activation levels in patients with acute
coronary artery disease. EGCG and
zinc may therefore represent effective agents for use in the prevention of I/R injury in clinical practice.