The synthetic prostaglandin E1 analogue rioprostil reduces the nephrotoxic potential of cyclosporine A.
Acute CyA nephrotoxicity involves alteration in the proximal tubule and leads to glomerular lesions. Administration of a vasodilatator agent such as the prostaglandin E1 analogue Rioprostil (Bayer AG, BAY 06893) might prevent preglomerular vasoconstriction and hence reduce cyclosporin nephrotoxicity. As an increased excretion of urinary enzymes as a consequence of CyA-nephrotoxicity is well known we investigated in 40 male Wistar rats the excretion of three urinary enzymes: the brush border enzyme gamma-glutamyltransferase (GGT), the leucine aminopeptidase (LAP), and the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG). Additionally we determined s-creatinine and CyA plasma level. The kidneys were studied histologically at the end of the study. Wistar rats receiving 20 or 50 mg CyA/kg/d showed a marked deterioration in renal function and an increase of all urinary enzymes determined. In the rats receiving 20 mg CyA/kg/d and Rioprostil (150 micrograms/d) renal function and the enzymes determined remained in the normal range. There was no change in the enzyme excretion and only a minor improvement of renal function in rats receiving 50 mg CyA/kg/d and Rioprostil. Histological findings showed prevention of CyA nephrotoxicity in the 20 mg/kg/d group and diminished renal damage in the 50 mg/kg/d group.
Metz-Kurschel
U
U
Department of Renal and Hypertensive Diseases, University Medical School, Essen, FRG.
Wagner
K
K
Mueller
M K
MK
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000097:blood / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D011458:Prostaglandins E / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D016630:Rioprostil; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D003524:Cyclosporins; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D016630:Rioprostil; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D007931:Leucyl Aminopeptidase