Catechin and proanthocyanidin B4 from grape seeds prevent doxorubicin-induced toxicity in cardiomyocytes.
The clinical use of doxorubicin, a highly active anticancer drug, is limited by its severe cardiotoxic side effects. Grape seed extract has been reported to exert protective effects on doxorubicin-induced cardiotoxicity. The cardiovascular protective effects of grape seed extract are believed to be ascribed to its antioxidative properties. A series of studies have has demonstrated that polyphenols are instrumental for the antioxidative properties of grape seed extract. This study was designed to investigate whether two major polyphenols isolated from grape seed extract, catechin and proanthocyanidin B4 (Pc B(4)), had protective effects against doxorubicin-induced toxicity in cardiomyocytes and their underlying mechanisms. The results showed that grape seed polyphenols catechin and Pc B(4) pretreatment would protect cardiomyocytes against doxorubicin-induced toxicity by decreasing reactive oxygen species generation as well as the number of apoptotic cells, preventing DNA fragmentation, regulating the expression levels of the pro-apoptotic protein Bax-alpha and the anti-apoptotic protein Bcl-2, and inhibiting apoptotic signaling pathways.
Du
Yu
Y
Department of Natural Products, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
Lou
Hongxiang
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D059808:Polyphenols; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects; D027843:Vitis / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D044945:Proanthocyanidins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C532119:proanthocyanidin B4; D004317:Doxorubicin; D002392:Catechin