Cardioprotective effects of epigallocatechin-3-gallate against doxorubicin-induced cardiomyocyte injury.
Doxorubicin-induced generation of reactive oxygen species is a leading cause of cardiomyopathy, the major side-effect limiting the clinical use of this anti-cancer drug. Epigallocatechin-3-gallate (EGCG), a main catechin in green tea that possesses a strong antioxidant property. This study aims to investigate whether EGCG can protect cardiac myocytes against doxorubicin-induced myocyte injury. Myocyte viability was measured with an MTT assay. Reactive oxygen species were measured with fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Myocyte shortening and intracellular Ca(2+) levels were determined with a spectrofluorometer connected to a video edge detection system. EGCG concentration-dependently increased cell viability and inhibited the generation of reactive oxygen species in doxorubicin-treated myocytes. Doxorubicin significantly decreased the amplitudes of cell shortening, the maximum velocity of cell contraction (+dl/dt) and relaxation (-dl/dt) in electrically-stimulated myocytes in the presence or absence of isoprenaline, which was attenuated by EGCG. The present data suggest that EGCG may protect myocytes against oxidative stress-induced cellular injury in doxorubicin-treated cardiac myocytes. The effect of EGCG on Ca(2+) handling was also examined. EGCG increased the amplitudes of both electrically- and caffeine-induced Ca(2+) transients in doxorubicin-treated myocytes, suggesting that EGCG may reverse doxorubicin-induced intracellular Ca(2+) depletion in the sarcoplasmic reticulum. We found in the present study that EGCG may protect heart against doxorubicin-induced myocyte injury by improving Ca(2+) handling through scavenging reactive oxygen species. Our results imply that EGCG may be used together with doxorubicin to minimize its cardiac toxic effects.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
Jin
J
Zheng
Hui Ching Michelle
HC
Lee
Mohamad Mukmin
MM
Bin Sattar
Yu
Y
Huang
Jin-Song
JS
Bian
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D002392:Catechin; C045651:epigallocatechin gallate