title: Erythropoietin protects against doxorubicin-induced heart failure.
abstract: The hormone erythropoietin (EPO) has been demonstrated to have cardioprotective properties. The present study investigates the role of EPO to prevent heart failure following cancer treatment with doxorubicin [adriamycin (AD)]. Male Wistar rats (150 ± 10 g) were treated with saline (vehicle control group); with EPO, subcutaneously at 1,000 IU/kg body wt, three times per week for 4 wk (EPO group); with adriamycin, intraperitoneally at 2.5 mg/kg body wt, three times per week for 2 wk (AD group); and with adriamycin and EPO (EPO-AD group). Echocardiographic measurements showed that EPO-AD treatment prevented the AD-induced decline in cardiac function. Each of the hearts was then exposed to ischemia and reperfusion during Langendorff perfusion. The percentage of recovery after ischemia-reperfusion was significantly greater in EPO-AD than the AD-treated group for left ventricular developed pressure, maximal increase in pressure, and rate pressure product. The level of oxidative stress was significantly higher in AD (5 μM for 24 h)-exposed isolated cardiomyocytes; EPO (5 U/ml for 48 h) treatment prevented this. EPO treatment also decreased AD-induced cardiomyocyte apoptosis, which was associated with the decrease in the Bax-to-Bcl2 ratio and caspase-3 activation. Immunostaining of myocardial tissue for CD31 showed a significant decrease in the number of capillaries in AD-treated animals. EPO-AD treatment restored the number of capillaries. In conclusion, EPO treatment effectively prevented AD-induced heart failure. The protective effect of EPO was associated with a decreased level of oxidative stress and apoptosis in cardiomyocytes as well as improved myocardial angiogenesis.
authors: Department of Physiology, Faculty of Medicine, Cairo University, Egypt. haniaammar@yahoo.com
authors: Hania Ibrahim
authors: HI
authors: Ammar
authors: Soliman
authors: S
authors: Saba
authors: Rasha Ibrahim
authors: RI
authors: Ammar
authors: Laila Ahmed
authors: LA
authors: Elsayed
authors: Wael Botros Abu-Alyamin
authors: WB
authors: Ghaly
authors: Sanjiv
authors: S
authors: Dhingra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004317:Doxorubicin; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D006333:Heart Failure / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004921:Erythropoietin; D004317:Doxorubicin; C505410:Casp3 protein, rat; D053148:Caspase 3