| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892
Adriamycin is an anthracycline drug with a wide spectrum of clinical antineoplastic activity. However, the usefulness of the drug is limited by its dose-dependent cardiotoxicity. Adriamycin-stimulated free radical formation has been suggested as one of the mechanisms for its cardiotoxic effects. In order to evaluate this underlying mechanism, we have perfused rat hearts with Adriamycin, using a modified Langendorf technique, and the free radicals formed were analyzed by electron spin resonance spectroscopy using spin-trapping techniques. Our studies show that Adriamycin stimulated the formation of ·OH in the heart, and the maximum ·OH was formed with 1 µM of the drug. The addition of superoxide dismutase (600 units/ml) inhibited the hydroxyl radical formation by 2-to 3-fold, while catalase (550 units/ml) abolished it completely, showing the intermediacy of superoxide and H2O2. Furthermore, ICRF-187, an iron chelator and a cytotoxic drug, was also an effective inhibitor of .OH formation in the rat heart. The heart rate was not significantly modified by all the above experiments. This study demonstrates that Adriamycin stimulates the formation of ·OH in the isolated rat heart and suggests that this mechanism may be significant in Adriamycin-induced cardiotoxicity.
1 To whom requests for reprints should be addressed, at Clinical Pharmacology Branch, National Cancer Institute, Bldg. 10, Rm. 6N 119, Bethesda, MD 20892.
Received 2/ 3/88. Revised 5/10/88. Accepted 5/27/88.
This article has been cited by other articles:
|
|
 |
|
  O. S. Bains, R. H. Takahashi, T. A. Pfeifer, T. A. Grigliatti, R. E. Reid, and K. W. Riggs Two Allelic Variants of Aldo-Keto Reductase 1A1 Exhibit Reduced in Vitro Metabolism of Daunorubicin Drug Metab. Dispos., May 1, 2008; 36(5): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rudzinski, M. Ciesielczyk, W. Religa, Z. Bednarkiewicz, and M. Krzeminska-Pakula Doxorubicin-induced ventricular arrhythmia treated by implantation of an automatic cardioverter-defibrillator Europace, May 1, 2007; 9(5): 278 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tokarska-Schlattner, M. Zaugg, R. da Silva, E. Lucchinetti, M. C. Schaub, T. Wallimann, and U. Schlattner Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H37 - H47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Conklin Coenzyme Q10 for Prevention of Anthracycline-Induced Cardiotoxicity Integr Cancer Ther, June 1, 2005; 4(2): 110 - 130. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Nozaki, T. Shishido, Y. Takeishi, and I. Kubota Modulation of Doxorubicin-Induced Cardiac Dysfunction in Toll-Like Receptor-2-Knockout Mice Circulation, November 2, 2004; 110(18): 2869 - 2874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Duquaine, G. A Hirsch, A. Chakrabarti, Z. Han, C. Kehrer, R. Brook, J. Joseph, A. Schott, B Kalyanaraman, J. Vasquez-Vivar, et al. Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase Vascular Medicine, May 1, 2003; 8(2): 101 - 107. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Yamanaka, T. Tatsumi, J. Shiraishi, A. Mano, N. Keira, S. Matoba, J. Asayama, S. Fushiki, H. Fliss, and M. Nakagawa Amlodipine inhibits doxorubicin-induced apoptosis in neonatal rat cardiac myocytes J. Am. Coll. Cardiol., March 5, 2003; 41(5): 870 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, Z. Chen, C. C. Chua, Y.-S. Ma, G. A. Youngberg, R. Hamdy, and B. H. L. Chua Melatonin as an effective protector against doxorubicin-induced cardiotoxicity Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H254 - H263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Zima, V. Tesar, R. Sherwood, A. Sood, L.-C. Au, P. J. Richardson, and V. R. Preedy Acute Dosage With Dexrazoxane, but not Doxorubicin, Is Associated With Increased Rates of Hepatic Protein Synthesis in vivo Toxicol Pathol, October 1, 2001; 29(6): 591 - 599. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Batist, G. Ramakrishnan, C. S. Rao, A. Chandrasekharan, J. Gutheil, T. Guthrie, P. Shah, A. Khojasteh, M. K. Nair, K. Hoelzer, et al. Reduced Cardiotoxicity and Preserved Antitumor Efficacy of Liposome-Encapsulated Doxorubicin and Cyclophosphamide Compared With Conventional Doxorubicin and Cyclophosphamide in a Randomized, Multicenter Trial of Metastatic Breast Cancer J. Clin. Oncol., March 1, 2001; 19(5): 1444 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Forrest, B. Gonzalez, W. Tseng, X. Li, and J. Mann Human Carbonyl Reductase Overexpression in the Heart Advances the Development of Doxorubicin-induced Cardiotoxicity in Transgenic Mice Cancer Res., September 1, 2000; 60(18): 5158 - 5164. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. R Jonas, A. B Puckett, D. P Jones, D. P Griffith, E. E Szeszycki, G. F Bergman, C. E Furr, C. Tyre, J. L Carlson, J. R Galloway, et al. Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients Am. J. Clinical Nutrition, July 1, 2000; 72(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arai, A. Yoguchi, T. Takizawa, T. Yokoyama, T. Kanda, M. Kurabayashi, and R. Nagai Mechanism of Doxorubicin-Induced Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase Gene Transcription Circ. Res., January 7, 2000; 86(1): 8 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. ANDRIEU-ABADIE, J.-P. JAFFRÉZOU, S. HATEM, G. LAURENT, T. LEVADE, and J.-J. MERCADIER L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation FASEB J, September 1, 1999; 13(12): 1501 - 1510. [Abstract] [Full Text]
|
|
|
|
|
|
D. B. Sawyer, R. Fukazawa, M. A. Arstall, and R. A. Kelly Daunorubicin-Induced Apoptosis in Rat Cardiac Myocytes Is Inhibited by Dexrazoxane Circ. Res., February 19, 1999; 84(3): 257 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Venditti, M Balestrieri, T De Leo, and S Di Meo Free radical involvement in doxorubicin-induced electrophysiological alterations in rat papillary muscle fibres Cardiovasc Res, June 1, 1998; 38(3): 695 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Lim, D. Masin, T. D. Madden, and M. B. Bally Influence of Drug Release Characteristics on the Therapeutic Activity of Liposomal Mitoxantrone J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 566 - 573. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Jeyaseelan, C. Poizat, H.-Y. Wu, and L. Kedes Molecular Mechanisms of Doxorubicin-induced Cardiomyopathy. SELECTIVE SUPPRESSION OF REISKE IRON-SULFUR PROTEIN, ADP/ATP TRANSLOCASE, AND PHOSPHOFRUCTOKINASE GENES IS ASSOCIATED WITH ATP DEPLETION IN RAT CARDIOMYOCYTES J. Biol. Chem., February 28, 1997; 272(9): 5828 - 5832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dunn Doxorubicin-Induced Cardiomyopathy Journal of Pediatric Oncology Nursing, January 1, 1994; 11(4): 152 - 160. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
