Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats

C. Esposito, F. Grosjean, M. Torreggiani, V. Esposito, F. Mangione, L. Villa, G. Sileno, R. Rosso, N. Serpieri, M. Molinaro, G. Fasoli, A. Dal Canton

Research output: Contribution to journalArticle

Abstract

Background: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. Methods: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-β, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. Results: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 μl/min, p <0.05; 126 ± 170 vs. 567 ± 374 μl/min, p <0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-β expression and matrix deposition. Only sirolimus increased metalloprotease activity. Conclusions: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

Original languageEnglish
Pages (from-to)239-249
Number of pages11
JournalAmerican Journal of Nephrology
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Immunosuppressive drugs
  • Ischemia-reperfusion injury
  • Metalloprotease activity

ASJC Scopus subject areas

  • Nephrology

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