Linked Life Data

11448472

Source:http://linkedlifedata.com/resource/pubmed/id/11448472

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2001-7-12
pubmed:abstractText
The cardiotoxicity of the anticancer drug doxorubicin may be related to its main metabolite doxorubicinol. In this study, the acute effects of doxorubicinol on excitation-contraction coupling in isolated guinea pig ventricular myocytes were investigated and compared with doxorubicin using the whole-cell patch-clamp-, fura-2 fluorescence- and cell-edge tracking techniques. Both drugs were applied intracellularly by diffusion from the patch electrode for 15--20 min. Doxorubicin (100 microM) prolonged the action potential duration (APD) by 31% and enhanced cell shortening by 26%. Contrary to doxorubicin, doxorubicinol (10 microM) shortened APD by 25% and decreased cell shortening by 31%. APD shortening by doxorubicinol was due to an increase of the delayed rectifier K(+) current. Neither the inward rectifier K(+) current nor the L-type Ca(2+) current was influenced by doxorubicinol. The decline in cell shortening induced by doxorubicinol was not exclusively due to APD shortening because doxorubicinol reduced the peak Ca(2+) transient by 23% in cells clamped with an action potential of constant duration. Despite opposite effects on APD and contractility, both doxorubicin and doxorubicinol produced a considerable delay in the activation and inactivation of contraction and Ca(2+) transient, compatible with an impaired function of the sarcoplasmic reticulum. It is suggested that doxorubicinol-induced APD shortening may amplify the detrimental effects of both doxorubicin and doxorubicinol on sarcoplasmic reticulum Ca(2+) load and hence on contractile function. The accumulation of doxorubicinol in the cardiac myocytes may play an important role in the time-dependent development of doxorubicin-induced ventricular dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
423
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-107
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Effects of doxorubicinol on excitation--contraction coupling in guinea pig ventricular myocytes.
pubmed:affiliation
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung Pharmakologie für Pharmazeuten, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't