| Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals. | |
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MedLine Citation:
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PMID: 1928418 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of free radicals in adriamycin (Adr)-induced acute myocardial changes was examined by using different antioxidants. Exposure of papillary muscles to Adr (100 microM) in a tissue bath for 60 min reduced developed force by 42%, increased lipid peroxidation by 200%, and resulted in characteristic ultrastructural changes. Catalase (4 x 10(4) U/l), an enzyme effective in the hydrolysis of hydrogen peroxide (H2O2), was more effective in maintaining the developed force than mannitol (20 mM), a hydroxyl radical scavenger. A small protection of developed force seen with superoxide dismutase (1.2 x 10(5) U/l), a quencher of superoxide radical, was evident for the first 15 min only. Only catalase and mannitol showed significant protection against Adr-induced increase in lipid peroxidation. Ultrastructural changes due to Adr alone included mitochondrial swelling, intramitochondrial granules, vacuolization, and disruption of sarcomeres. All of these changes were reduced in the presence of both catalase and mannitol, whereas superoxide dismutase was without any effect. Complete structural or functional protection was not seen with any of the antioxidants used in the study. Although both H2O2 and hydroxyl radical appear to be involved in Adr-induced deleterious effects, data on developed force also indicate that H2O2 may have a major role in mediating the acute effects of Adr in vitro. |
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Authors:
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V Lee; A K Randhawa; P K Singal |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of physiology Volume: 261 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1991 Oct |
Date Detail:
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Created Date: 1991-11-20 Completed Date: 1991-11-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: H989-95 Citation Subset: IM |
Affiliation:
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Cardiovascular Sciences Division, St. Boniface General Hospital Research Centre, Winnipeg, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiomyopathies / chemically induced* Catalase / pharmacology Cytoplasmic Granules / ultrastructure Doxorubicin* / pharmacology Free Radical Scavengers Free Radicals Male Malondialdehyde / analysis Mannitol / pharmacology Mitochondria, Heart / ultrastructure Oxygen / pharmacology* Papillary Muscles / chemistry, drug effects, ultrastructure Rats Rats, Inbred Strains Superoxide Dismutase / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Free Radical Scavengers; 0/Free Radicals; 23214-92-8/Doxorubicin; 542-78-9/Malondialdehyde; 69-65-8/Mannitol; 7782-44-7/Oxygen; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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