title: [Value of protecting mitochondrial functions during treatment with cyclosporin A].
abstract: The use of cyclosporin A is often limited by its nephrotoxicity. This dose-dependent toxicity can occur in all kinds of transplantation and is reversed with drug withdrawal. Cyclosporin A induces a vasoconstriction leading to an increase of renal vascular resistance and a reduction of glomerular filtration. Histochemical studies show mitochondrial alterations and an excess of cytosolic and mitochondrial calcium leading to a decrease of ATP synthesis. Two strategies can be evoked for limiting cyclosporin-A-induced nephrotoxicity. First, the use of drugs counteracting the vasoconstriction has been proposed. Second, drugs acting by restoration of ATP synthesis could also be of interest. For example, calcium channel blockers may be used for limiting the Ca2+ fluxes into cells. Another way to protect ATP synthesis is to inhibit the cyclosporin-A-induced increase of mitochondrial Ca2+ concentrations; Trimetazidine has shown its efficiency in vitro for protecting mitochondria against these modifications of Ca2+ homeostasis and is under clinical evaluation.
authors.affiliation: Service Hospitalo-Universitaire de Pharmacologie, Université de Paris XII, Créteil, France.
authors.forename: N
authors.initials: N
authors.lastname: Simon
authors.forename: E
authors.initials: E
authors.lastname: Albengres
authors.forename: J
authors.initials: J
authors.lastname: Barré
authors.forename: P
authors.initials: P
authors.lastname: Jolliet
authors.forename: S
authors.initials: S
authors.lastname: Urien
authors.forename: A
authors.initials: A
authors.lastname: Settaf
authors.forename: J P
authors.initials: JP
authors.lastname: Tillement
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D016377:Organ Transplantation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
vernacular_title: L'intérêt de la protection des fonctions mitochondriales au cours d'un traitement par la cyclosporine A.