[Effects of trimetazidine on altered functions of rat kidney induced by cyclosporine].
A mitochondrial dysfunction has been suggested to explain chronic renal toxicity observed in ciclosporine A therapy. Our study has investigated whether trimetazidine allows inhibition of mitochondrial alteration induced by ciclosporine A. Oxidative phosphorylation was measured by polarography, calcium fluxes by a specific calcium electrode and the mitochondrial swelling by determination of the optical density at 520 nm, using a spectrophotometer. The ciclosporine A effect on the respiratory control was fully inhibited by trimetazidine (EC50 5.10 x 10(-7) M; Emax 11 per cent). Trimetazidine also inhibited the ciclosporine effects on calcium fluxes, i.e. calcium accumulation into the matrix and delay of efflux. Trimetazidine allows a decrease of mitochondrial dysfunction induced by ciclosporine A.
Simon
N
N
Service Hospitalo-Universitaire de Pharmacologie, Université de Paris XII, Centre Hospitalier Intercommunal, 40 avenue de Verdun, F94000 Créteil, France.
Morin
C
C
Bruguerolle
B
B
Tillement
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D016572:Cyclosporine; D014292:Trimetazidine; D002118:Calcium