Cytoprotective effect of anthocyanins against doxorubicin-induced toxicity in H9c2 cardiomyocytes in relation to their antioxidant activities.
The effect of six anthocyanidins and seven anthocyanins against doxorubicin (Dox)-induced cardiotoxicity in relation to their antioxidant properties was investigated in H9c2 cardiomyocytes. The exposure to Dox, a highly effective cytotoxic agent against cancer cells, induced significant cell death, intracellular reactive oxygen species (ROS), and lipid peroxidation in non-tumorigenic cardiac cell culture. All anthocyanidins (50 and/or 100 microM) significantly increased cell survival up to 40% compared to the Dox-treated controls. Especially, cyanidin and delphinidin, which have an ortho-dihydroxyl moiety (3',4'-OH) on the flavylium skeleton, demonstrated the most potent protection against cytotoxicity (EC(50) of 113 and 179 microM, respectively) as well as lipid peroxidation induced by Dox treatment. In contrast, seven anthocyanins having a glycosidic moiety showed little effect in cytoprotection and lipid peroxidation, although they markedly blocked intracellular ROS generation. All anthocyanidins and anthocyanins had higher TEAC values than ascorbic acid, and efficaciously scavenged superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), peroxynitrite (ONOO(-)) and nitric oxide (NO), but not hydroxyl radical (OH()). Their O(2)(-) scavenging activity was well correlated with the observed cytoprotection (r=0.67, p<0.05). These results suggest that anthocyanidins can ameliorate Dox-induced cardiotoxicity by, at least in part, scavenging of O(2)(-) generated by Dox.
Choi
Eun Hye
EH
Food Safety Research Division, Korea Food Research Institute, San 46-1, Backhyun, Bundang-gu, Sungnam, Kyonggi-do 463-746, South Korea.
Chang
Hyun-Joo
HJ
Cho
Jae Young
JY
Chun
Hyang Sook
HS
D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System / Q000187:drug effects; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009569:Nitric Oxide / Q000737:chemistry; D030421:Peroxynitrous Acid / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000872:Anthocyanins; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D004317:Doxorubicin