title: Misoprostol Partially Inhibits the Renal Scarring of Chronic Cyclosporine Nephrotoxicity.
abstract: Chronic cyclosporine (CY) nephrotoxicity is a well-known complication of this immunosuppressive agent, which may, in part, be attributed to abnormalities in renal prostaglandin content. We utilized misoprostol (M), a prostaglandin E(1) analog, in a rat model of chronic CY toxicity at 7 and 28 days to determine effectiveness in prevention of the renal damage. After 7 days, there were no differences in weight change, creatinine clearance, or renal scarring in rats treated with vehicle (V), CY, or CY + M; however, renal procollagen alpha 1(I) mRNA levels were increased in CY versus V rats (p < 0.05). In contrast, after 28 days CY rats had significant reductions in weight gain, glomerular filtration rate, and renal blood flow with increases in renal scarring and procollagen alpha 1 (IV) mRNA levels (all p < 0.05 versus V). Addition of M resulted in partial but significant improvement in GFR, RBF, and procollagen alpha 1(IV) mRNA levels, with lessening of the renal scarring. Skin fibroblasts also were incubated with CY and M to assess impact on procollagen MRNA levels. CY augmented fibroblast procollagen mRNA levels which enhanced by a large dose of M, but inhibited with a moderate dose. These data suggest that M improves renal scarring induced by CY by hemodynamic and/or direct effects.
authors.affiliation: Department of Pathology, Cedars--Sinai Medical Center, Los Angeles, USA and UCLA School of Medicine, Los Angeles, USA.
authors.forename: Cynthia C.
authors.initials: CC
authors.lastname: Nast
authors.forename: Raimund
authors.initials: R
authors.lastname: Hirschberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Artishevsky
authors.forename: Sharon G.
authors.initials: SG
authors.lastname: Adler