Effect of cyclosporin A and different vehicles on ATP production in mitochondria isolated from the rat kidney cortex.
Isolated rat kidney mitochondria were exposed in vitro to cyclosporin A and three different vehicles, ethanol, DMSO and cremophor. Spontaneous ATP production and oxidative phosphorylation were measured with a bioluminometric method. Both ethanol and cremophor caused a slight (4-7%) decrease in spontaneous ATP production, and also cyclosporin A itself had a minimal effect. On the other hand DMSO had an opposite effect, causing an increase of about 20%. Cyclosporin A showed a dose dependent inhibition of oxidative phosphorylation, being most pronounced when dissolved in ethanol. Cremophor, the castor oil used in commercial preparations caused per se almost a 40% inhibition of the oxidative phosphorylation.
Nässberger
L
L
Department of Medical Microbiology, University of Lund, Sweden.
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D014677:Pharmaceutical Vehicles; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C022131:cremophor; D000431:Ethanol; D011092:Polyethylene Glycols; D000255:Adenosine Triphosphate; D004121:Dimethyl Sulfoxide