[Pharmacological modulation of mitochondrial oxidative phosphorylation: inhibition by cyclosporine A, restoration by trimetazidine].
When applied to a suspension of isolated mitochondria extracted from rat hepatocytes, cyclosporine A decreases ATP synthesis and induces Ca2+ accumulation. Both effects are considered as possible determinants, even partly, of renal toxicity observed with this drug. Trimetazidine antagonizes both effects at concentrations easily reached in man with therapeutic dosages. It is concluded that the association of both drugs may improve the renal tolerance of Cyclosporine A.
Tillement
J P
JP
Service de Pharmacologie, Faculté de Médecine de Paris XII.
Crevat
A
A
Testa
B
B
Le Ridant
A
A
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D014292:Trimetazidine / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D014292:Trimetazidine