EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats
Abstract
Aim: 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. Conclusion: 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.
Keywords:
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. Conclusion: 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.