Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies

Journal of Molecular and Cellular Cardiology

Volumn 52, Issue 6, 2012, Pages 1213-1225

  Octavia, Yanti ^a   Tocchetti, Carlo G ^b   Gabrielson, Kathleen L ^c   Janssens, Stefan ^d   Crijns, Harry J ^a   Moens, An L ^a  

^a MAASTRICHT UNIVERSITY   (Netherlands)

^b NATIONAL CANCER INSTITUTE   (Italy)

^c DEPARTMENT OF PATHOLOGY   (United States)

^d UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Anthracyclines; Cardioprotection; Cardiotoxicity; Doxorubicin; Heart failure; Oxidative stress

Indexed keywords

ANANDAMIDE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BIOLOGICAL MARKER; CALCIUM ION; CANNABINOID 1 RECEPTOR ANTAGONIST; CAPTOPRIL; CARVEDILOL; CERAMIDE; DICLOFENAC; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DOBUTAMINE; DOXORUBICIN; ENALAPRIL; ENDOTHELIN 1; EPIRUBICIN; FERROUS ION; MONOXERUTIN; NEU DIFFERENTIATION FACTOR; NITRIC OXIDE SYNTHASE; OXIDOREDUCTASE; PLACEBO; RAMIPRIL; RAZOXANE; REACTIVE OXYGEN METABOLITE; RECOMBINANT ERYTHROPOIETIN; RESVERATROL; SILDENAFIL; ZOFENOPRIL;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADJUVANT THERAPY; ADRENERGIC STIMULATION; ADVANCED CANCER; ANEMIA; APOPTOSIS; CALCIUM CELL LEVEL; CARDIAC IMAGING; CARDIAC RESYNCHRONIZATION THERAPY; CARDIOMYOPATHY; CARDIOTOXICITY; CLINICAL EFFECTIVENESS; CLINICAL FEATURE; CONGESTIVE HEART FAILURE; CONTINUOUS INFUSION; DIAGNOSTIC VALUE; DNA DEGRADATION; DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; ECG ABNORMALITY; EXTRACELLULAR MATRIX; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE INJURY; HEART PROTECTION; HODGKIN DISEASE; HUMAN; LOW DRUG DOSE; LYMPHOMA; MITOCHONDRIAL TOXICITY; MOLECULAR INTERACTION; NONHUMAN; OPTIMAL DRUG DOSE; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PATHOGENESIS; PHARMACOLOGIC STRESS TESTING; PRIORITY JOURNAL; REVIEW; SOLID TUMOR; STRESS ECHOCARDIOGRAPHY;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CARDIOMYOPATHIES; DOXORUBICIN; HUMANS;

EID: 84860523994     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2012.03.006     Document Type: Review

References (162)

1. Allen A. The cardiotoxicity of chemotherapeutic drugs. Semin Oncol 1992, 19:529-542.
2. Jain D. Cardiotoxicity of doxorubicin and other anthracycline derivatives. J Nucl Cardiol 2000, 7:53-62.
3. Lipshultz S.E., Lipsitz S.R., Mone S.M., Goorin A.M., Sallan S.E., Sanders S.P., et al. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 1995, 332:1738-1743.
4. Lanzarini L., Bossi G., Laudisa M.L., Klersy C., Arico M. Lack of clinically significant cardiac dysfunction during intermediate dobutamine doses in long-term childhood cancer survivors exposed to anthracyclines. Am Heart J 2000, 140:315-323.
5. Sorensen K., Levitt G., Sebag-Montefiore D., Bull C., Sullivan I. Cardiac function in Wilms' tumor survivors. J Clin Oncol 1995, 13:1546-1556.
6. Silber J.H., Jakacki R.I., Larsen R.L., Goldwein J.W., Barber G. Increased risk of cardiac dysfunction after anthracyclines in girls. Med Pediatr Oncol 1993, 21:477-479.
7. Biancaniello T., Meyer R.A., Wong K.Y., Sager C., Kaplan S. Doxorubicin cardiotoxicity in children. J Pediatr 1980, 97:45-50.
8. Hershman D.L., McBride R.B., Eisenberger A., Tsai W.Y., Grann V.R., Jacobson J.S. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol 2008, 26:3159-3165.
9. Godoy L.Y., Fukushige J., Igarashi H., Matsuzaki A., Ueda K. Anthracycline-induced cardiotoxicity in children with malignancies. Acta Paediatr Jpn 1997, 39:188-193.
10. Pein F., Sakiroglu O., Dahan M., Lebidois J., Merlet P., Shamsaldin A., et al. Cardiac abnormalities 15years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy. Br J Cancer 2004, 91:37-44.
11. Saltiel E., McGuire W. Doxorubicin (adriamycin) cardiomyopathy. West J Med 1983, 139:332-341.
12. Singal P.K., Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998, 339:900-905.
13. Kremer L.C., van Dalen E.C., Offringa M., Voute P.A. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Ann Oncol 2002, 13:503-512.
14. Xu M.F., Tang P.L., Qian Z.M., Ashraf M. Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. Life Sci 2001, 68:889-901.
15. Simunek T., Sterba M., Popelova O., Adamcova M., Hrdina R., Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 2009, 61:154-171.
16. Horenstein M.S., Vander Heide R.S., L'Ecuyer T.J. Molecular basis of anthracycline-induced cardiotoxicity and its prevention. Mol Genet Metab 2000, 71:436-444.
17. Doroshow J.H., Locker G.Y., Myers C.E. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest 1980, 65:128-135.
18. Goormaghtigh E., Chatelain P., Caspers J., Ruysschaert J.M. Evidence of a complex between adriamycin derivatives and cardiolipin: possible role in cardiotoxicity. Biochem Pharmacol 1980, 29:3003-3010.
19. Schlame M., Rua D., Greenberg M.L. The biosynthesis and functional role of cardiolipin. Prog Lipid Res 2000, 39:257-288.
20. Kashfi K., Israel M., Sweatman T.W., Seshadri R., Cook G.A. Inhibition of mitochondrial carnitine palmitoyltransferases by adriamycin and adriamycin analogues. Biochem Pharmacol 1990, 40:1441-1448.
21. Ventura-Clapier R., Garnier A., Veksler V. Energy metabolism in heart failure. J Physiol 2004, 555:1-13.
22. Cole M.P., Chaiswing L., Oberley T.D., Edelmann S.E., Piascik M.T., Lin S.M., et al. The protective roles of nitric oxide and superoxide dismutase in adriamycin-induced cardiotoxicity. Cardiovasc Res 2006, 69:186-197.
23. Minotti G., Menna P., Salvatorelli E., Cairo G., Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004, 56:185-229.
24. Papadopoulou L.C., Theophilidis G., Thomopoulos G.N., Tsiftsoglou A.S. Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression. Biochem Pharmacol 1999, 57:481-489.
25. Carvalho R.A., Sousa R.P., Cadete V.J., Lopaschuk G.D., Palmeira C.M., Bjork J.A., et al. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy. Toxicology 2010, 270:92-98.
26. Suliman H.B., Carraway M.S., Ali A.S., Reynolds C.M., Welty-Wolf K.E., Piantadosi C.A. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J Clin Invest 2007, 117:3730-3741.
27. Piantadosi C.A., Carraway M.S., Babiker A., Suliman H.B. Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res 2008, 103:1232-1240.
28. Pani G., Bedogni B., Anzevino R., Colavitti R., Palazzotti B., Borrello S., et al. Deregulated manganese superoxide dismutase expression and resistance to oxidative injury in p53-deficient cells. Cancer Res 2000, 60:4654-4660.
29. Kim D.S., Kim H.R., Woo E.R., Kwon D.Y., Kim M.S., Chae S.W., et al. Protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity. Eur J Pharmacol 2006, 541:24-32.
30. Xiong Y., Liu X., Lee C.P., Chua B.H., Ho Y.S. Attenuation of doxorubicin-induced contractile and mitochondrial dysfunction in mouse heart by cellular glutathione peroxidase. Free Radic Biol Med 2006, 41:46-55.
31. Vasquez-Vivar J., Martasek P., Hogg N., Masters B.S., Pritchard K.A., Kalyanaraman B. Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry 1997, 36:11293-11297.
32. Kalivendi S.V., Kotamraju S., Zhao H., Joseph J., Kalyanaraman B. Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium. J Biol Chem 2001, 276:47266-47276.
33. Moens A.L., Leyton-Mange J.S., Niu X., Yang R., Cingolani O., Arkenbout E.K., et al. Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor. J Mol Cell Cardiol 2009, 47:576-585.
34. Neilan T.G., Blake S.L., Ichinose F., Raher M.J., Buys E.S., Jassal D.S., et al. Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Circulation 2007, 116:506-514.
35. Duquaine D., Hirsch G.A., Chakrabarti A., Han Z., Kehrer C., Brook R., et al. Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase. Vasc Med 2003, 8:101-107.
36. Mukhopadhyay P., Rajesh M., Batkai S., Kashiwaya Y., Hasko G., Liaudet L., et al. Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro. Am J Physiol Heart Circ Physiol 2009, 296:H1466-H1483.
37. Fu J., Yamamoto K., Guan Z.W., Kimura S., Iyanagi T. Human neuronal nitric oxide synthase can catalyze one-electron reduction of adriamycin: role of flavin domain. Arch Biochem Biophys 2004, 427:180-187.
38. Liu B., Li H., Qu H., Sun B. Nitric oxide synthase expressions in ADR-induced cardiomyopathy in rats. J Biochem Mol Biol 2006, 39:759-765.
39. Deng S., Kruger A., Kleschyov A.L., Kalinowski L., Daiber A., Wojnowski L. Gp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH. Free Radic Biol Med 2007, 42:466-473.
40. Gilleron M., Marechal X., Montaigne D., Franczak J., Neviere R., Lancel S. NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis. Biochem Biophys Res Commun 2009, 388:727-731.
41. Wojnowski L., Kulle B., Schirmer M., Schluter G., Schmidt A., Rosenberger A., et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 2005, 112:3754-3762.
42. Blanco J.G., Leisenring W.M., Gonzalez-Covarrubias V.M., Kawashima T.I., Davies S.M., Relling M.V., et al. Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer. Cancer 2008, 112:2789-2795.
43. May P.M., Williams G.K., Williams D.R. Solution chemistry studies of adriamycin-iron complexes present in vivo. Eur J Cancer 1980, 16:1275-1276.
44. Kappus H., Muliawan H., Scheulen M.E. In vivo studies on adriamycin-induced lipid peroxidation and effects of ferrous ions. Dev Toxicol Environ Sci 1980, 8:635-638.
45. Xu X., Persson H.L., Richardson D.R. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol 2005, 68:261-271.
46. Minotti G., Recalcati S., Mordente A., Liberi G., Calafiore A.M., Mancuso C., et al. The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium. FASEB J 1998, 12:541-552.
47. Miranda C.J., Makui H., Soares R.J., Bilodeau M., Mui J., Vali H., et al. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood 2003, 102:2574-2580.
48. Panjrath G.S., Patel V., Valdiviezo C.I., Narula N., Narula J., Jain D. Potentiation of doxorubicin cardiotoxicity by iron loading in a rodent model. J Am Coll Cardiol 2007, 49:2457-2464.
49. Barton J.C., Bertoli L.F. Transfusion iron overload in adults with acute leukemia: manifestations and therapy. Am J Med Sci 2000, 319:73-78.
50. Dhalla N.S., Temsah R.M., Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens 2000, 18:655-673.
51. Bjelogrlic S.K., Radic J., Jovic V., Radulovic S. Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice. Basic Clin Pharmacol Toxicol 2005, 97:311-319.
52. Nitobe J., Yamaguchi S., Okuyama M., Nozaki N., Sata M., Miyamoto T., et al. Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes. Cardiovasc Res 2003, 57:119-128.
53. Liu B., Bai Q.X., Chen X.Q., Gao G.X., Gu H.T. Effect of curcumin on expression of survivin, Bcl-2 and Bax in human multiple myeloma cell line. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2007, 15:762-766.
54. Vedam K., Nishijima Y., Druhan L.J., Khan M., Moldovan N.I., Zweier J.L., et al. Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice. Am J Physiol Heart Circ Physiol 2010, 298:H1832-41.
55. Shan Y.X., Liu T.J., Su H.F., Samsamshariat A., Mestril R., Wang P.H. Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells. J Mol Cell Cardiol 2003, 35:1135-1143.
56. Fan G.C., Zhou X., Wang X., Song G., Qian J., Nicolaou P., et al. Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity. Circ Res 2008, 103:1270-1279.
57. Kim S.C., Stice J.P., Chen L., Jung J.S., Gupta S., Wang Y., et al. Extracellular heat shock protein 60, cardiac myocytes, and apoptosis. Circ Res 2009, 105:1186-1195.
58. Rayner K., Chen Y.X., McNulty M., Simard T., Zhao X., Wells D.J., et al. Extracellular release of the atheroprotective heat shock protein 27 is mediated by estrogen and competitively inhibits acLDL binding to scavenger receptor-A. Circ Res 2008, 103:133-141.
59. Nozaki N., Shishido T., Takeishi Y., Kubota I. Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2-knockout mice. Circulation 2004, 110:2869-2874.
60. Riad A., Bien S., Gratz M., Escher F., Westermann D., Heimesaat M.M., et al. Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice. Eur J Heart Fail 2008, 10:233-243.
61. Chen C., Jin Y. Effects of oxymatrine on expression of nuclear factor kappa B in kidneys of rats with adriamycin-induced chronic renal fibrosis. Nan Fang Yi Ke Da Xue Xue Bao 2007, 27:345-348.
62. Wang S., Kotamraju S., Konorev E., Kalivendi S., Joseph J., Kalyanaraman B. Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide. Biochem J 2002, 367:729-740.
63. Ueno M., Kakinuma Y., Yuhki K., Murakoshi N., Iemitsu M., Miyauchi T., et al. Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo. J Pharmacol Sci 2006, 101:151-158.
64. Youn H.J., Kim H.S., Jeon M.H., Lee J.H., Seo Y.J., Lee Y.J., et al. Induction of caspase-independent apoptosis in H9c2 cardiomyocytes by adriamycin treatment. Mol Cell Biochem 2005, 270:13-19.
65. Bruynzeel A.M., Abou El Hassan M.A., Torun E., Bast A., van der Vijgh W.J., Kruyt F.A. Caspase-dependent and -independent suppression of apoptosis by monoHER in doxorubicin treated cells. Br J Cancer 2007, 96:450-456.
66. Maejima Y., Adachi S., Morikawa K., Ito H., Isobe M. Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation. J Mol Cell Cardiol 2005, 38:163-174.
67. d'Anglemont de Tassigny A., Berdeaux A., Souktani R., Henry P., Ghaleh B. The volume-sensitive chloride channel inhibitors prevent both contractile dysfunction and apoptosis induced by doxorubicin through PI3kinase, Akt and Erk 1/2. Eur J Heart Fail 2008, 10:39-46.
68. Kalivendi S.V., Konorev E.A., Cunningham S., Vanamala S.K., Kaji E.H., Joseph J., et al. Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium. Biochem J 2005, 389:527-539.
69. Arai M., Yoguchi A., Takizawa T., Yokoyama T., Kanda T., Kurabayashi M., et al. Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription. Circ Res 2000, 86:8-14.
70. Holmberg S.R., Williams A.J. Patterns of interaction between anthraquinone drugs and the calcium-release channel from cardiac sarcoplasmic reticulum. Circ Res 1990, 67:272-283.
71. Saeki K., Obi I., Ogiku N., Shigekawa M., Imagawa T., Matsumoto T. Doxorubicin directly binds to the cardiac-type ryanodine receptor. Life Sci 2002, 70:2377-2389.
72. 2+ exchange of dog heart sarcolemmal vesicles. FEBS Lett 1981, 130:184-186.
73. Keung E.C., Toll L., Ellis M., Jensen R.A. L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations. J Clin Invest 1991, 87:2108-2113.
74. 2+ release channel from skeletal muscle sarcoplasmic reticulum. J Biol Chem 1995, 270:25557-25563.
75. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B.A., et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000, 403:98-103.
76. Jang Y.M., Kendaiah S., Drew B., Phillips T., Selman C., Julian D., et al. Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. FEBS Lett 2004, 577:483-490.
77. Sawyer D.B., Zuppinger C., Miller T.A., Eppenberger H.M., Suter T.M. Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation 2002, 105:1551-1554.
78. Lim C.C., Zuppinger C., Guo X., Kuster G.M., Helmes M., Eppenberger H.M., et al. Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes. J Biol Chem 2004, 279:8290-8299.
79. Solem L.E., Heller L.J., Wallace K.B. Dose-dependent increase in sensitivity to calcium-induced mitochondrial dysfunction and cardiomyocyte cell injury by doxorubicin. J Mol Cell Cardiol 1996, 28:1023-1032.
80. 2+ increase by doxorubicin in cardiac myocytes. Biochem J 1992, 281(Pt 3):871-878.
81. Gabrielson K., Bedja D., Pin S., Tsao A., Gama L., Yuan B., et al. Heat shock protein 90 and ErbB2 in the cardiac response to doxorubicin injury. Cancer Res 2007, 67:1436-1441.
82. Peng X., Guo X., Borkan S.C., Bharti A., Kuramochi Y., Calderwood S., et al. Heat shock protein 90 stabilization of ErbB2 expression is disrupted by ATP depletion in myocytes. J Biol Chem 2005, 280:13148-13152.
83. Negro A., Brar B.K., Gu Y., Peterson K.L., Vale W., Lee K.-F. erbB2 is required for G protein-coupled receptor signaling in the heart. Proc Natl Acad Sci 2006, 103:15889-15893.
84. Tripathy D., Seidman A., Keefe D., Hudis C., Paton V., Lieberman G. Effect of cardiac dysfunction on treatment outcomes in women receiving trastuzumab for HER2-overexpressing metastatic breast cancer. Clin Breast Cancer 2004, 5:293-298.
85. Tokarska-Schlattner M., Zaugg M., da Silva R., Lucchinetti E., Schaub M.C., Wallimann T., et al. Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply. Am J Physiol Heart Circ Physiol 2005, 289:H37-H47.
86. Keller A.M., Jackson J.A., Peshock R.M., Rehr R.B., Willerson J.T., Nunnally R.L., et al. Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity. Magn Reson Med 1986, 3:834-843.
87. Nicolay K., Aue W.P., Seelig J., van Echteld C.J., Ruigrok T.J., de Kruijff B. Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity. Biochim Biophys Acta 1987, 929:5-13.
88. Bordoni A., Biagi P., Hrelia S. The impairment of essential fatty acid metabolism as a key factor in doxorubicin-induced damage in cultured rat cardiomyocytes. Biochim Biophys Acta 1999, 1440:100-106.
89. Chatham J.C., Cousins J.P., Glickson J.D. The relationship between cardiac function and metabolism in acute adriamycin-treated perfused rat hearts studied by 31P and 13C NMR spectroscopy. J Mol Cell Cardiol 1990, 22:1187-1197.
90. Thomas C., Carr A.C., Winterbourn C.C. Free radical inactivation of rabbit muscle creatinine kinase: catalysis by physiological and hydrolyzed ICRF-187 (ICRF-198) iron chelates. Free Radic Res 1994, 21:387-397.
91. Mihm M.J., Yu F., Weinstein D.M., Reiser P.J., Bauer J.A. Intracellular distribution of peroxynitrite during doxorubicin cardiomyopathy: evidence for selective impairment of myofibrillar creatine kinase. Br J Pharmacol 2002, 135:581-588.
92. Suzuki T., Miyauchi T. A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes. Am J Physiol Regul Integr Comp Physiol 2001, 280:R1399-R1406.
93. Picard P., Smith P.J., Monge J.C., Rouleau J.L., Nguyen Q.T., Calderone A., et al. Coordinated upregulation of the cardiac endothelin system in a rat model of heart failure. J Cardiovasc Pharmacol 1998, 31(Suppl. 1):S294-S297.
94. Pieske B., Beyermann B., Breu V., Loffler B.M., Schlotthauer K., Maier L.S., et al. Functional effects of endothelin and regulation of endothelin receptors in isolated human nonfailing and failing myocardium. Circulation 1999, 99:1802-1809.
95. Sayed-Ahmed M.M., Khattab M.M., Gad M.Z., Osman A.M. Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy. Pharmacol Toxicol 2001, 89:140-144.
96. Luscher T.F., Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000, 102:2434-2440.
97. Miller W.L., Cavero P.G., Aarhus L.L., Heublein D.M., Burnett J.C. Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effects are attenuated by nitroglycerin in vivo. Am J Hypertens 1993, 6:156-163.
98. Bien S., Riad A., Ritter C.A., Gratz M., Olshausen F., Westermann D., et al. The endothelin receptor blocker bosentan inhibits doxorubicin-induced cardiomyopathy. Cancer Res 2007, 67:10428-10435.
99. Yang L.L., Gros R., Kabir M.G., Sadi A., Gotlieb A.I., Husain M., et al. Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice. Circulation 2004, 109:255-261.
100. Spinale F.G. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007, 87:1285-1342.
101. Goetzenich A., Hatam N., Zernecke A., Weber C., Czarnotta T., Autschbach R., et al. Alteration of matrix metalloproteinases in selective left ventricular adriamycin-induced cardiomyopathy in the pig. J Heart Lung Transplant 2009, 28:1087-1093.
102. Spallarossa P., Altieri P., Garibaldi S., Ghigliotti G., Barisione C., Manca V., et al. Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: the role of MAP kinases and NAD(P)H oxidase. Cardiovasc Res 2006, 69:736-745.
103. Tokarska-Schlattner M., Lucchinetti E., Zaugg M., Kay L., Gratia S., Guzun R., et al. Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes. Am J Physiol Regul Integr Comp Physiol 2010, 298:R1075-R1088.
104. Singh B.K., Pathan R.A., Pillai K.K., Haque S.E., Dubey K. Diclofenac sodium, a nonselective nonsteroidal anti-inflammatory drug aggravates doxorubicin-induced cardiomyopathy in rats. J Cardiovasc Pharmacol Feb 2010, 55(2):139-144.
105. Dowd N.P., Scully M., Adderley S.R., Cunningham A.J., Fitzgerald D.J. Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo. J Clin Invest 2001, 108:585-590.
106. Horie T., Ono K., Nishi H., Nagao K., Kinoshita M., Watanabe S., et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res 2010, 87(4):656-664.
107. Andrieu-Abadie N., Jaffrezou J.P., Hatem S., Laurent G., Levade T., Mercadier J.J. l-Carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation. FASEB J 1999, 13:1501-1510.
108. d'Anglemont de Tassigny A., Souktani R., Henry P., Ghaleh B., Berdeaux A. Volume-sensitive chloride channels (ICl,vol) mediate doxorubicin-induced apoptosis through apoptotic volume decrease in cardiomyocytes. Fundam Clin Pharmacol 2004, 18:531-538.
109. Mukhopadhyay P., Batkai S., Rajesh M., Czifra N., Harvey-White J., Hasko G., et al. Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity. J Am Coll Cardiol 2007, 50:528-536.
110. Mukhopadhyay P., Rajesh M., Batkai S., Patel V., Kashiwaya Y., Liaudet L., et al. CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes. Cardiovasc Res 2010, 85:773-784.
111. Hydock D.S., Lien C.Y., Hayward R. Anandamide preserves cardiac function and geometry in an acute doxorubicin cardiotoxicity rat model. J Cardiovasc Pharmacol Ther 2009, 14:59-67.
112. Torti F.M., Bristow M.M., Lum B.L., Carter S.K., Howes A.E., Aston D.A., et al. Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy. Cancer Res 1986, 46:3722-3727.
113. Bristow M.R. Toxic cardiomyopathy due to doxorubicin. Hosp Pract (Off Ed) 1982, 17:101-108. 10-1.
114. Takemura G., Fujiwara H. Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis 2007, 49:330-352.
115. Hengel C.L., Russell P.A., Gould P.A., Kaye D.M. Subacute anthracycline cardiotoxicity. Heart Lung Circ 2006, 15:59-61.
116. Saini J., Rich M.W., Lyss A.P. Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases. Ann Intern Med 1987, 106:814-816.
117. Cohen M., Kronzon I., Lebowitz A. Reversible doxorubicin-induced congestive heart failure. Arch Intern Med 1982, 142:1570-1571.
118. McKillop J.H., Bristow M.R., Goris M.L., Billingham M.E., Bockemuehl K. Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity. Am Heart J 1983, 106:1048-1056.
119. Tjeerdsma G., Meinardi M.T., van Der Graaf W.T., van Den Berg M.P., Mulder N.H., Crijns H.J., et al. Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables. Heart 1999, 81:419-423.
120. Panjrath G.S., Jain D. Monitoring chemotherapy-induced cardiotoxicity: role of cardiac nuclear imaging. J Nucl Cardiol 2006, 13:415-426.
121. Gabrielson K.L., Mok G.S., Nimmagadda S., Bedja D., Pin S., Tsao A., et al. Detection of dose response in chronic doxorubicin-mediated cell death with cardiac technetium 99m annexin V single-photon emission computed tomography. Mol Imaging 2008, 7:132-138.
122. Migrino R.Q., Aggarwal D., Konorev E., Brahmbhatt T., Bright M., Kalyanaraman B. Early detection of doxorubicin cardiomyopathy using two-dimensional strain echocardiography. Ultrasound Med Biol 2008, 34:208-214.
123. Klewer S.E., Goldberg S.J., Donnerstein R.L., Berg R.A., Hutter J.J. Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer. J Am Coll Cardiol 1992, 19:394-401.
124. Elbl L., Hrstkova H., Chaloupka V., Novotny J., Michalek J. The evaluation of left ventricular function in childhood cancer survivors by pharmacological stress echocardiography. Neoplasma 2003, 50:191-197.
125. Marchandise B., Schroeder E., Bosly A., Doyen C., Weynants P., Kremer R., et al. Early detection of doxorubicin cardiotoxicity: interest of Doppler echocardiographic analysis of left ventricular filling dynamics. Am Heart J 1989, 118:92-98.
126. Stoddard M.F., Seeger J., Liddell N.E., Hadley T.J., Sullivan D.M., Kupersmith J. Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans. J Am Coll Cardiol 1992, 20:62-69.
127. Lipshultz S.E., Rifai N., Dalton V.M., Levy D.E., Silverman L.B., Lipsitz S.R., et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004, 351:145-153.
128. Hayakawa H., Komada Y., Hirayama M., Hori H., Ito M., Sakurai M. Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer. Med Pediatr Oncol 2001, 37:4-9.
129. Suzuki T., Hayashi D., Yamazaki T., Mizuno T., Kanda Y., Komuro I., et al. Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 1998, 136:362-363.
130. Erttmann R., Erb N., Steinhoff A., Landbeck G. Pharmacokinetics of doxorubicin in man: dose and schedule dependence. J Cancer Res Clin Oncol 1988, 114:509-513.
131. Creech R.H., Catalano R.B., Shah M.K. An effective low-dose adriamycin regimen as secondary chemotherapy for metastatic breast cancer patients. Cancer 1980, 46:433-437.
132. Schroeder P.E., Hasinoff B.B. Metabolism of the one-ring open metabolites of the cardioprotective drug dexrazoxane to its active metal-chelating form in the rat. Drug Metab Dispos 2005, 33:1367-1372.
133. Hasinoff B.B. The hydrolysis activation of the doxorubicin cardioprotective agent ICRF-187 [+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane). Drug Metab Dispos 1990, 18:344-349.
134. Lebrecht D., Geist A., Ketelsen U.P., Haberstroh J., Setzer B., Walker U.A. Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats. Br J Pharmacol 2007, 151:771-778.
135. Barry E.V., Vrooman L.M., Dahlberg S.E., Neuberg D.S., Asselin B.L., Athale U.H., et al. Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J Clin Oncol 2008, 26:1106-1111.
136. Tebbi C.K., London W.B., Friedman D., Villaluna D., De Alarcon P.A., Constine L.S., et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol 2007, 25:493-500.
137. Hensley M.L., Hagerty K.L., Kewalramani T., Green D.M., Meropol N.J., Wasserman T.H., et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009, 27:127-145.
138. van Acker S.A., Voest E.E., Beems D.B., Madhuizen H.T., de Jong J., Bast A., et al. Cardioprotective properties of O-(beta-hydroxyethyl)-rutosides in doxorubicin-pretreated BALB/c mice. Cancer Res 1993, 53:4603-4607.
139. van Acker F.A., Hulshof J.W., Haenen G.R., Menge W.M., van der Vijgh W.J., Bast A. New synthetic flavonoids as potent protectors against doxorubicin-induced cardiotoxicity. Free Radic Biol Med 2001, 31:31-37.
140. van Acker S.A., Kramer K., Grimbergen J.A., van den Berg D.J., van der Vijgh W.J., Bast A. Monohydroxyethylrutoside as protector against chronic doxorubicin-induced cardiotoxicity. Br J Pharmacol 1995, 115:1260-1264.
141. van Acker S.A., Boven E., Kuiper K., van den Berg D.J., Grimbergen J.A., Kramer K., et al. Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin. Clin Cancer Res 1997, 3:1747-1754.
142. Bruynzeel A.M., Niessen H.W., Bronzwaer J.G., van der Hoeven J.J., Berkhof J., Bast A., et al. The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study. Br J Cancer 2007, 97:1084-1089.
143. Kalay N., Basar E., Ozdogru I., Er O., Cetinkaya Y., Dogan A., et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2006, 48:2258-2262.
144. Georgakopoulos P., Roussou P., Matsakas E., Karavidas A., Anagnostopoulos N., Marinakis T., et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol 2010, 85:894-896.
145. Tallaj J.A., Franco V., Rayburn B.K., Pinderski L., Benza R.L., Pamboukian S., et al. Response of doxorubicin-induced cardiomyopathy to the current management strategy of heart failure. J Heart Lung Transplant 2005, 24:2196-2201.
146. Jensen B.V., Nielsen S.L., Skovsgaard T. Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy. Lancet 1996, 347:297-299.
147. Sacco G., Bigioni M., Evangelista S., Goso C., Manzini S., Maggi C.A. Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. Eur J Pharmacol 2001, 414:71-78.
148. Al-Shabanah O., Mansour M., El-Kashef H., Al-Bekairi A. Captopril ameliorates myocardial and hematological toxicities induced by adriamycin. Biochem Mol Biol Int 1998, 45:419-427.
149. Sacco G., Mario B., Lopez G., Evangelista S., Manzini S., Maggi C.A. ACE inhibition and protection from doxorubicin-induced cardiotoxicity in the rat. Vascul Pharmacol 2009, 50:166-170.
150. Ibrahim M.A., Ashour O.M., Ibrahim Y.F., El-Bitar H.I., Gomaa W., Abdel-Rahim S.R. Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. Pharmacol Res 2009, 60:373-381.
151. Ramond A., Sartorius E., Mousseau M., Ribuot C., Joyeux-Faure M. Erythropoietin pretreatment protects against acute chemotherapy toxicity in isolated rat hearts. Exp Biol Med (Maywood) 2008, 233:76-83.
152. Engert A., Josting A., Haverkamp H., Villalobos M., Lohri A., Sokler M., et al. Epoetin alfa in patients with advanced-stage Hodgkin's lymphoma: results of the randomized placebo-controlled GHSG HD15EPO trial. J Clin Oncol 2010, 28:2239-2245.
153. Fisher P.W., Salloum F., Das A., Hyder H., Kukreja R.C. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation 2005, 111:1601-1610.
154. Di X., Gennings C., Bear H.D., Graham L.J., Sheth C.M., White K.L., et al. Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells. Breast Cancer Res Treat 2010, 124:349-360.
155. Das A., Durrant D., Mitchell C., Mayton E., Hoke N.N., Salloum F.N., et al. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction. Proc Natl Acad Sci U S A 2010, 107:18202-18207.
156. Gross G.J. Evidence for pleiotropic effects of phosphodiesterase-5 (PDE5) inhibitors: emerging concepts in cancer and cardiovascular medicine. Circ Res 2011, 108:1040-1041.
157. Tatlidede E., Sehirli O., Velioglu-Ogunc A., Cetinel S., Yegen B.C., Yarat A., et al. Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage. Free Radic Res 2009, 43:195-205.
158. Ajijola O.A., Nandigam K.V., Chabner B.A., Orencole M., Dec G.W., Ruskin J.N., et al. Usefulness of cardiac resynchronization therapy in the management of doxorubicin-induced cardiomyopathy. Am J Cardiol 2008, 101:1371-1372.
159. Ward K.M., Binns H., Chin C., Webber S.A., Canter C.E., Pahl E. Pediatric heart transplantation for anthracycline cardiomyopathy: cancer recurrence is rare. J Heart Lung Transplant 2004, 23:1040-1045.
160. van Dalen E.C., Michiels E.M., Caron H.N., Kremer L.C. Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev 2010, CD005006.
161. Suter T.M., Procter M., van Veldhuisen D.J., Muscholl M., Bergh J., Carlomagno C., et al. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol 2007, 25:3859-3865.
162. Eschenhagen T., Force T., Ewer M.S., de Keulenaer G.W., Suter T.M., Anker S.D., et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2011, 13:1-10.