title: Preventive effects of ellagic acid against doxorubicin-induced cardio-toxicity in mice.
abstract: Preventive effects of ellagic acid against doxorubicin-induced cardiac oxidative, inflammatory and apoptotic stress were examined. This agent at 0.25, 0.5 or 1% was added in feed and supplied to mice for 8 weeks, and followed by doxorubicin treatment. Ellagic acid intake increased its deposit in heart. Pre-intake of this compound at 0.5 and 1% significantly attenuated doxorubicin caused increase in plasma creatine phosphokinase activity. Doxorubicin treatment decreased glutathione content, increased reactive oxygen species (ROS), malonyldialdehyde (MDA), interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels, declined glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and enhanced xanthine oxidases (XO) activity in heart. Ellagic acid intake dose-dependently reserved glutathione content, lowered ROS and MDA levels, and reduced XO activity. This compound at 0.5 and 1% retained GPX and SOD activities, and decreased cytokines in heart. Doxorubicin treatment raised cardiac activity and protein production of caspase-3, nuclear factor kappa B (NF-κB) p50 and p65. Ellagic acid dose-dependently lowered caspase-3 activity and cleaved caspase-3 formation, and at 0.5 and 1% declined activity and protein level of NF-κB. Doxorubicin treatment also up-regulated cardiac expression of p-p38, p-ERK 1/2 and p-JNK, and ellagic acid at 0.5 and 1% suppressed p-p38 expression and at 1% down-regulated p-ERK 1/2 expression. These findings suggest that ellagic acid is a potent cardiac protective agent against doxorubicin.
authors: School of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
authors: Ming-Cheng
authors: MC
authors: Lin
authors: Mei-Chin
authors: MC
authors: Yin
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015415:Biomarkers; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents; D053148:Caspase 3 / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003402:Creatine Kinase / Q000378:metabolism; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D004610:Ellagic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D002316:Cardiotonic Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D004610:Ellagic Acid; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase; D020928:Mitogen-Activated Protein Kinases; D003402:Creatine Kinase; D053148:Caspase 3; D005978:Glutathione