EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats.
OBJECTIVE
To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis.


METHODS
Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2.


RESULTS
In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6 weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. In the Western blot analysis, EGCG significantly inhibited pressure overload-induced p53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry.


CONCLUSIONS
EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload induced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.
Sheng
Rui
R
Department of Pharmacology, Medical School of Soochow University, Suzhou 215123, China. sheng_rui@163.com
Gu
Zhen-lun
ZL
Xie
Mei-lin
ML
Zhou
Wen-xuan
WX
Guo
Ci-yi
CY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; D002392:Catechin; C045651:epigallocatechin gallate; D007770:L-Lactate Dehydrogenase