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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2003-9-23
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pubmed:abstractText |
The clinical use of doxorubicin (DOX), an anthracycline chemotherapeutic agent, is limited by cardiotoxicity. The possible involvement of iron in DOX-induced cardiotoxicity became evident from studies in which iron chelators were shown to be cardioprotective. Iron overload is found in hereditary hemochromatosis, a genetic disorder prevalent in individuals of European descent. We hypothesized that Hfe deficiency may increase susceptibility to DOX-induced toxicity. Acute cardiotoxicity and iron changes were studied after treatment with DOX in Hfe knock-out (Hfe-/-) mice and wild-type mice. DOX-induced iron metabolism changes were intensified in Hfe-/- mice, which accumulated significantly more iron in the heart, liver, and pancreas, but less in the spleen compared with wild-type mice. In addition, Hfe-deficient mice exhibited significantly greater sensitivity to DOX-induced elevations in serum creatine kinase and aspartate aminotransferase. Increased mortality after chronic DOX treatment was observed in Hfe-/- mice and Hfe+/-mice compared with wild-type mice. DOX-treated Hfe-/- mice had a higher degree of mitochondrial damage and iron deposits in the heart than did wild-type mice. These data demonstrate that Hfe deficiency in mice increases susceptibility to DOX-induced cardiotoxicity and suggest that genetic mutations related to defects in iron metabolism may contribute to its cardiotoxicity in humans.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartate Aminotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Creatine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Hfe protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transferrin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2574-80
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12805055-Alanine Transaminase,
pubmed-meshheading:12805055-Animals,
pubmed-meshheading:12805055-Antibiotics, Antineoplastic,
pubmed-meshheading:12805055-Aspartate Aminotransferases,
pubmed-meshheading:12805055-Creatine Kinase,
pubmed-meshheading:12805055-Doxorubicin,
pubmed-meshheading:12805055-Female,
pubmed-meshheading:12805055-Genetic Predisposition to Disease,
pubmed-meshheading:12805055-Histocompatibility Antigens Class I,
pubmed-meshheading:12805055-Iron,
pubmed-meshheading:12805055-Iron Metabolism Disorders,
pubmed-meshheading:12805055-Liver,
pubmed-meshheading:12805055-Membrane Proteins,
pubmed-meshheading:12805055-Mice,
pubmed-meshheading:12805055-Mice, Mutant Strains,
pubmed-meshheading:12805055-Mitochondria,
pubmed-meshheading:12805055-Myocardium,
pubmed-meshheading:12805055-Survival Rate,
pubmed-meshheading:12805055-Transferrin
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pubmed:year |
2003
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pubmed:articleTitle |
Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin.
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pubmed:affiliation |
Hôpital Notre-Dame, Centre Hospitalier de l'Université de Montréal, QC, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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