Prevention of cyclosporine (CyA) nephrotoxicity by synthetic prostaglandins.
Acute and chronic nephrotoxicity directly attributable to cyclosporine (CyA) administration remains an obstacle to its successful use. The studies presented in this report characterize the cytoprotective properties of 16,16-dimethyl prostaglandin E2 in a lethal CyA-induced nephrotoxic rodent model. Wistar-Furth rats (200-250 g) receiving CyA alone (100 mg/kg/day) showed marked deterioration in renal function with severe histologic renal lesions and death of the majority of animals by day 7. The prostaglandin treated group (10/micrograms/kg/day) administered concomitantly with CyA demonstrated near normal renal function and histology by the eighth day after CyA discontinuation, and in a significant improvement in animal survival of 85% (p less than 0.001, n = at least 20 rats/group). These studies demonstrate a novel approach to a major problem with cyclosporine and should have exciting clinical potential.
Makowka
L
L
Lopatin
W
W
Gilas
T
T
Falk
J
J
Phillips
M J
MJ
Falk
R
R
D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003524:Cyclosporins; D011459:Prostaglandins E, Synthetic; D011465:Prostaglandins, Synthetic; C017244:16,16-dimethylprostaglandin E; D003404:Creatinine