Protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity.
Adriamycin is a potent antitumor drug that is known to cause severe cardiotoxicity. This study examined the protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity. Calceolarioside significantly inhibited the adriamycin induced cell death and caspase-3 activation, which may be explained by the increase in Bcl-2 expression and the inhibition of Bax expression. Calceolarioside increased the expression of the antioxidant molecules and decreased the level of intracellular reactive oxygen species. Catalase, glutathione, N-acetylcysteine, Mannitol and Mn-TBAP (manganese (III) tetrakis-(4-benzoic acid) porphyrin) significantly inhibited the H9c2 cell death induced by adriamycin. Calceolarioside significantly inhibited H9c2 cell death, and was more effective than that observed with the other antioxidants, including probucol, ascorbic acid, and alpha-tocopherol. Overall, these results suggest that calceolarioside can inhibit adriamycin-induced apoptosis in H9c2 cardiomyocyte by inhibiting the generation of reactive oxygen species. Calceolarioside may be a potential candidate agent that inhibits cardiomyocyte-toxicity in adriamycin-exposed patients.
Kim
Do-Sung
DS
Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk University, Jeonju, Chonbuk 560-180, South Korea.
Kim
Hyung-Ryong
HR
Woo
Eun-Rhan
ER
Kwon
Dae-Young
DY
Kim
Myung-Sunny
MS
Chae
Soo-Wan
SW
Chae
Han-Jung
HJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002109:Caffeic Acids; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C083066:calceolarioside A; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3