In vitro comparative study on nephrotoxicity of cyclosporine A, its metabolites M1, M17, M21, and its analogues cyclosporines C and D in suspensions of rabbit renal cortical cells.
The potential nephrotoxicity of cyclosporine A (CsA), its three main metabolites: M1, M17 and M21, and its two analogues: cyclosporines C and D (CsC, CsD) was evaluated in vitro in suspensions of freshly isolated rabbit renal proximal tubular cells. This assessment involved the measure of enzyme release in the incubation media and the determination of Na+/K(+)-ATPase activity and glutathione content directly in the tubular cells. In vitro nephrotoxicity results of the six compounds tested could be respectively schematized as: CsA > CsD > CsC > M21 > M17, M1 It would be interesting to promote the study of promising CsC because of its low nephrotoxicity and its high immunosuppressive potency as previously reported.
Sadeg
N
N
Laboratoire de Toxicologie (EA 207), Faculté de Pharmacie, Paris, France.
Pham-Huy
C
C
Martin
C
C
Warnet
J M
JM
Claude
J R
JR
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000378:metabolism / Q000633:toxicity; D003524:Cyclosporins / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013329:Structure-Activity Relationship; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D003524:Cyclosporins; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione