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Identification of novel indicators of cyclosporine A nephrotoxicity in a CD-1 mouse model
Date Issued
2011-04-15
Date Available
2011-04-04T10:06:59Z
Abstract
The calcineurin inhibitor cyclosporine A (CsA) is a widely used immunosuppressive agent. However,nephrotoxicity is a serious side effect observed in patients which limits clinical use of CsA. CsA nephrotoxicity is associated with tubulointerstitial injury progressing to nephropathy. This is typically diagnosed by invasive
renal biopsy and is often only detected when the disease process is well advanced. Therefore identification of
novel, early indicators of CsA nephrotoxicity could be clinically advantageous. This study aimed to establish a
murine model of CsA nephrotoxicity and to identify urinary proteins that may indicate the onset of CsAinduced
nephropathy using 2-D gel electrophoresis. CsA nephrotoxicity was induced in CD-1 mice by daily
CsA administration for 4 weeks. By week 4, elevated serum creatinine and proteinuria were observed after
CsA treatment indicating significant renal dysfunction. Decreased cadherin-1, increased α-smooth muscle
actin and fibroblast specific protein 1 in kidney tissue indicated disruption of normal tubular architecture.
Alterations in podocin and uromodulin were also observed which may indicate damage to other segments of
the nephron. Proteomic analysis of urine identified a number of differentially regulated proteins that may be
involved in early CsA nephropathy including cadherin 1, superoxide dismutase and vinculin. These findings
suggest novel mechanisms of CsA nephrotoxicity and identify novel potential markers of the disease.
Sponsorship
Science Foundation Ireland
Higher Education Authority
Irish Research Council for Science, Engineering and Technology
European Research Council
Health Research Board
Type of Material
Journal Article
Publisher
Elsevier
Journal
Toxicology and Applied Pharmacology
Volume
252
Issue
2
Start Page
201
End Page
210
Copyright (Published Version)
2011 Elsevier Inc.
Subject – LCSH
Cadherins
Connective tissues--Growth
Fibroblast growth factors
Transforming growth factors
Nephrotoxicology--Diagnosis
Web versions
Language
English
Status of Item
Peer reviewed
ISSN
0041-008X
This item is made available under a Creative Commons License
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