| The effect of doxorubicin and its analogue mitoxantrone on cardiac muscle and on serum lipids: an experimental study. | |
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MedLine Citation:
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PMID: 12014656 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This experimental study compares the toxic effect of the two cytotoxic drugs, doxorubicin and mitoxantrone, on cardiac muscle and on serum lipids. The cardiotoxicity of doxorubicin due to the cumulative effect of repeated administration is known. A relative compound, mitoxantrone, is a member of the androstenedione class of synthetic antitumor agents and its chemical structure, based on a quinone ring, is similar to that of doxorubicin. Doxorubicin has wide application in cancer medicine but its dose-limited cardiac effect creates the need for a substitute compound. Mitoxantrone, also an effective agent, may be able to cover this need. Three groups of 35 Wistar rats were used during this experimental study of 12 weeks' duration. Drugs at a certain calculated dose were administered once weekly. Group A animals were treated with doxorubicin, Group B with mitoxantrone and Group C, the controls, with normal saline. Six animals per group were autopsied after euthanasia in the 3rd, 6th, 8th, 10th and 12th weeks. Cardiac muscle, liver and other organs, plus blood, were removed for macro- and microscopical, and biochemical tests. Our results showed that there was a cumulative toxic effect of doxorubicin (adriamycin) on cardiac muscle starting in the 6th week which gradually increased to Grade III lesions by the 10th and 12th weeks. In parallel, an increase in serum lipids, mainly cholesterol and triglycerides was observed. Mitoxantrone-treated animals showed moderate cardiotoxic lesions (but not cumulative) and no increase in serum lipids. In vitro testing of oxygen-free radical production showed high production by doxorubicin and very low production by mitoxantrone. Thus, mitoxantrone appears to be safer than doxorubicin. |
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Authors:
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George Koutinos; George P Stathopoulos; Ismene Dontas; Despina Perrea-Kotsarelis; Ephrosini Couris; Panayotis E Karayannacos; George Deliconstantinos |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Anticancer research Volume: 22 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 2002 Mar-Apr |
Date Detail:
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Created Date: 2002-05-16 Completed Date: 2002-06-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 815-20 Citation Subset: IM |
Affiliation:
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Hippokration Hospital, 2nd Medical Division, University of Athens School of Medicine, Greece. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / toxicity* Antineoplastic Agents / toxicity* Doxorubicin / toxicity* Female Heart / drug effects* Lipids / blood* Male Mitoxantrone / toxicity* Myocardium / metabolism, pathology Oxidative Stress Rats Rats, Wistar Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 0/Lipids; 0/Reactive Oxygen Species; 23214-92-8/Doxorubicin; 65271-80-9/Mitoxantrone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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