Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1997-10-23
pubmed:abstractText
Histologic, nick end labeling for apoptosis and electron microscopic studies were made of the heart, kidney and small intestine in spontaneously hypertensive rats (SHR) treated for 12 weeks with doxorubicin (1 mg/kg/week), mitoxantrone (0.5 or 0.25 mg/kg/week) or saline (controls). Semiquantitative scoring showed that the severity of the cardiac lesions produced by doxorubicin was comparable to that resulting from 0.5 mg/kg mitoxantrone, but greater than that induced by 0.25 mg/kg mitoxantrone (to which it is therapeutically equivalent). The nephropathy and the intestinal toxicity produced by doxorubicin were also more severe than those resulting from either dose of mitoxantrone. Apoptosis of cardiac myocytes was not induced by either drug, but involved cardiac dendritic cells in SHR given doxorubicin. Apoptosis in renal tubular epithelium was comparable in SHR given doxorubicin and the higher dose of mitoxantrone. Doxorubicin induced more frequent apoptosis in intestinal epithelium than did the higher dose of mitoxantrone. We also show that mitoxantrone and iron(III) form a strong 2:1 complex, in which the drug may be acting as a tridentate ligand. This complex, like the iron(III)-doxorubicin complex, may be capable of redox cycling and producing reactive oxygen intermediates (ROI) that damage tissue. Decreased formation of ROI by mitoxantrone may account for its reduced cardiotoxicity compared to that of doxorubicin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 1997 Academic Press Limited.
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2415-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the Fe(III)-mitoxantrone complex.
pubmed:affiliation
Food and Drug Administration, Laurel, Maryland 20708, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't