title: Doxorubicin induces mitochondrial permeability transition and contractile dysfunction in the human myocardium.
abstract: In human atrial trabeculae, we examined the effects of doxorubicin on the isometric force of contraction, mitochondrial respiration, membrane potential and calcium retention capacity. Compared with untreated controls, doxorubicin induced contractile dysfunction and depression of mitochondrial respiration. Mitochondria isolated from doxorubicin-treated human atrial trabeculae displayed reduced transmembrane potential and calcium retention capacity. Cyclosporine A, a mitochondrial membrane transition pore opening blocker, prevented mitochondrial dysfunction and impaired contractile performance induced by doxorubicin. The study suggests that a mitochondrial membrane transition pore opening is involved in the development of doxorubicin cardiotoxicity in human hearts.
authors.affiliation: Department of Physiology, Faculty of Medicine, University Lille 2, IFR 114 IMPRT, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Montaigne
authors.forename: Xavier
authors.initials: X
authors.lastname: Marechal
authors.forename: Sebastien
authors.initials: S
authors.lastname: Preau
authors.forename: Riadh
authors.initials: R
authors.lastname: Baccouch
authors.forename: Thomas
authors.initials: T
authors.lastname: Modine
authors.forename: George
authors.initials: G
authors.lastname: Fayad
authors.forename: Steve
authors.initials: S
authors.lastname: Lancel
authors.forename: Remi
authors.initials: R
authors.lastname: Neviere
mesh_terms: D018943:Anthracyclines / Q000633:toxicity; D054715:Cardiotoxins / Q000633:toxicity*; D016572:Cyclosporine / Q000494:pharmacology; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure
chemical_list: D018943:Anthracyclines; D054715:Cardiotoxins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D004317:Doxorubicin; D016572:Cyclosporine