The effect of α-melanocyte-stimulating hormone on renal tubular cell apoptosis and tubulointerstitial fibrosis in cyclosporine A nephrotoxicity

So Young Lee, Sang Kyung Jo, Won Yong Cho, Hyoung Kyu Kim, Nam Hee Won

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27 Citations (Scopus)

Abstract

Background. The pathogenesis of cyclosporine A (CsA)-induced nephrotoxicity has been known to be secondary to hemodynamic changes, but increasing evidence indicates that CsA has a direct toxicity to renal tubular cells, leading to their apoptosis and tubulointerstitial fibrosis. This study evaluated the mechanism for CsA-induced tubular cell apoptosis, tubulointerstitial fibrosis and its associated proteins, and the therapeutic effects of α-melanocyte- stimulating hormone (MSH) on them. Methods. Male Sprague-Dawley rats fed with a low-sodium diet were divided into three treatment groups: group A (vehicle-injected group), group B (CsA 15 mg/kg-injected group), and group C(CsA+α-MSH-injected group). After 42 days, creatinine clearance; blood CsA level; apoptosis; inflammation and tubulointerstitial fibrosis in renal tissue; and the expression of Bax, Bcl2, Fas, FasL, and transforming growth factor (TGF)-β protein were determined. Results. CsA-induced tubular cell apoptosis; cellular infiltration; and increase of Fas, Bax, TGF-β protein expression with significant tubulointerstitial fibrosis, and reduced Bcl2 protein expression. α-MSH treatment prevented the Bax and TGF-β protein increase and induced Bcl2 protein increase, together with reduction of apoptosis, inflammation, and tubulointerstitial fibrosis. Conclusions. These findings suggest that chronic CsA nephrotoxicity is related to Bax and Bcl2-related apoptosis pathways, and that α-MSH can attenuate the CsA-induced tubulointerstitial fibrosis as well as tubular cell apoptosis.

Original languageEnglish
Pages (from-to)1756-1764
Number of pages9
JournalTransplantation
Volume78
Issue number12
DOIs
Publication statusPublished - 2004 Dec 27

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Keywords

  • α-Melanocyte-stimulating hormone
  • Apoptosis
  • Bax/Bcl
  • Cyclosporine
  • Fas/FasL

ASJC Scopus subject areas

  • Transplantation

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