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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: Mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL
Fundamental and Clinical Pharmacology, Volume 28, No. 2, Year 2014
Notification
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Description
Chronic immunosuppressive treatment was suspected to alter maximal muscle oxidative capacity (Vmax) of heart transplant recipients, leading to a limitation of their exercise tolerance. It remains undefined whether the mitochondrial respiratory chain (MRC) of right ventricle (RV) and vastus lateralis (VL) muscles were altered by immunosuppressants and/or their vehicles. Vmax was measured polarographically in saponin-skinned fibres of RV and VL biopsies of patients and compared with Vmax of healthy VL and myocardium. Effects of increasing concentrations (1-10-100 μM) of Sandimmune®, its vehicle, Cyclosporine (CsA) in ethanol (EtOH), or EtOH alone were tested. The vehicle's effects on MRC complexes were investigated using specific substrates and inhibitors. Ten months after grafting, Vmax of RV and VL of immunosuppressed patients were similar to their Vmax at time of transplantation and to that of control tissues. In Vitro, Sandimmune® significantly decreased Vmax while CsA in EtOH or EtOH exerted small and similar effects. Effects of the vehicle were higher than (RV) or identical to (VL) those of Sandimmune®. The sites of action of the vehicle on MRC were located on complexes I and IV. While unchanged under chronic immunosuppressive therapy, Vmax of RV and VL muscles was depressed by acute exposure to intravenous Sandimmune® in vitro, an effect attributed to its vehicle by inhibition of complexes I and IV of the MRC. This work provides an in vitro proof of a toxic effect on the mitochondria respiratory chain of the vehicle used in the intravenous formulation of Sandimmune® but with no clinical consequences in chronically immunosuppressed patients. © 2012 Société Française de Pharmacologie et de Thérapeutique.
Authors & Co-Authors
N'guessan, Benoit Banga
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Cote D'ivoire, Abidjan
Universite D'abobo-adjame
Ghana, Accra
University of Ghana
Sanchez, Hervé
France, Grenoble
Crssa
Zoll, Joffrey
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Ribera, Florence
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Dufour, Stéphane
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Lampert, Eliane
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Kindo, Michel
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Gény, Bernard
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Ventura-Clapier, Renée E.
France, Gif-sur-yvette
Université Paris-saclay
Mettauer, Bertrand
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
France, Colmar
Hôpitaux Civils de Colmar
Statistics
Citations: 10
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1111/fcp.12002
ISSN:
07673981
e-ISSN:
14728206
Research Areas
Environmental
Noncommunicable Diseases