Document Detail


Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals.
MedLine Citation:
PMID:  1928418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
V Lee; A K Randhawa; P K Singal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  261     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1991 Oct 
Date Detail:
Created Date:  1991-11-20     Completed Date:  1991-11-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H989-95     Citation Subset:  IM    
Affiliation:
Cardiovascular Sciences Division, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
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MeSH Terms
Descriptor/Qualifier:
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:
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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