Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats.
Epigallocatechin-3-gallate (EGCG) is the most prominent catechin in green tea. EGCG has been shown to modulate numerous molecular targets in the setting of inflammation and cancer. These molecular targets have also been demonstrated to be important participants in reperfusion injury, hence this study examines the effects of EGCG in myocardial reperfusion injury. Male Wistar rats were subjected to myocardial ischemia (30 min) and reperfusion (up to 2 h). Rats were treated with EGCG (10 mg/kg intravenously) or with vehicle at the end of the ischemia period followed by a continuous infusion (EGCG 10 mg/kg/h) during the reperfusion period. In vehicle-treated rats, extensive myocardial injury was associated with tissue neutrophil infiltration as evaluated by myeloperoxidase activity, and elevated levels of plasma creatine phosphokinase. Vehicle-treated rats also demonstrated increased plasma levels of interleukin-6. These events were associated with cytosol degradation of inhibitor kappaB-alpha, activation of IkappaB kinase, phosphorylation of c-Jun, and subsequent activation of nuclear factor-kappaB and activator protein-1 in the infarcted heart. In vivo treatment with EGCG reduced myocardial damage and myeloperoxidase activity. Plasma IL-6 and creatine phosphokinase levels were decreased after EGCG administration. This beneficial effect of EGCG was associated with reduction of nuclear factor-kB and activator protein-1 DNA binding. The results of this study suggest that EGCG is beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the NF-kappaB and AP-1 pathway.
Aneja
Rajesh
R
Department of Pediatrics, Division of Critical Care Medicine-OSB5, Cincinnati Children's Hospital Medical Center and College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. rajaneja@pol.net
Hake
Paul W
PW
Burroughs
Timothy J
TJ
Denenberg
Alvin G
AG
Wong
Hector R
HR
Zingarelli
Basilia
B
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D005419:Flavonoids; D051550:I-kappa B Kinase; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D010636:Phenols; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013662:Tea / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
D005419:Flavonoids; D015850:Interleukin-6; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D016755:Proto-Oncogene Proteins c-jun; D013662:Tea; D018808:Transcription Factor AP-1; D002392:Catechin; C045651:epigallocatechin gallate; D009195:Peroxidase; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D003402:Creatine Kinase