Linked Life Data

21605084

Source:http://linkedlifedata.com/resource/pubmed/id/21605084

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-7-12
pubmed:abstractText
We tested whether inhibition of mitochondrial membrane potential dissipation by CsA (ciclosporin A) would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and subchronic models of doxorubicin exposition were performed in mice with either a single intraperitoneal bolus (10 mg/kg of body weight, intraperitoneal) or one injection of 4 mg·kg(-1) of body weight·week(-1) during 5 weeks. Follow-up was at 1.5 weeks and 16 weeks in acute and subchronic models respectively. Mice received either CsA (1 mg/kg of body weight, intraperitoneal on alternate days) or saline until follow-up. Heart function was evaluated by echocardiography. Mitochondrial measurements included oxygen consumption, membrane potential and externally added calcium-induced mitochondrial permeability transition. Mitochondrial mass was evaluated by transmission electronic microscopy and mtDNA (mitochondrial DNA) content. Mitochondrial dynamics were detected as the expression of GTPases involved in mitochondrial fusion and fission. In both the acute and chronic models, doxorubicin decreased left ventricular fractional shortening and survival. Heart function and survival were improved by CsA, but not by tacrolimus (FK506), a ciclosporin derivative with no inhibitory effect on the mitochondrial transition pore. In the acute model, doxorubicin exposure was associated with increased mtDNA content, mitochondrial fragmentation and changes in mitochondrial fusion- and fission-related transcripts [increases in Mfn2 (mitofusin 2), Opa1 (optic atrophy 1 homologue) and Fis1 (fission 1 homologue), and no changes in Drp1 (dynamin 1-like)]. CsA did not alter mitochondrial biogenesis, but prevented mitochondrial fragmentation and partially restored the mitochondrial energy-producing capacity. These findings suggest that in vivo CsA treatment may limit MPTP (mitochondrial permeability transition pore) opening, mitochondrial potential loss and contractile depression in acute and chronic models of cardiac toxicity induced by doxorubicin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1470-8736
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
405-13
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Doxorubicin-induced cardiac dysfunction is attenuated by ciclosporin treatment in mice through improvements in mitochondrial bioenergetics.
pubmed:affiliation
Department of Physiology (EA 4484), Faculty of Medicine, University of the North of France, place de Verdun, Lille cedex 59045, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't