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Table of Contents
Vol. 35, No. 2, 2012
Issue release date: February 2012
Section title: Original Report: Laboratory Investigation
Am J Nephrol 2012;35:103–113
(DOI:10.1159/000334935)

Rosuvastatin Preserves Renal Structure following Unilateral Ureteric Obstruction in the Neonatal Rat

Mazzei L.J.a · García I.M.a · Altamirano L.c · Docherty N.G.d · Manucha W.a–c
Áreas deaFisiopatología y bFarmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, y cIMBECU-CONICET – National Council of Scientific and Technical Research of Argentina, Buenos Aires, Argentina; dDepartment of Physiology, School of Medicine, Trinity College, Dublin, Ireland

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Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: September 20, 2011
Accepted: November 08, 2011
Published online: December 29, 2011
Issue release date: February 2012

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 1

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN

Abstract

Background/Aims: Unilateral ureteric obstruction (UUO) in neonatal rodents can be used as a paradigm for in utero obstruction in humans and a platform for studying the potential of novel therapies for congenital obstructive nephropathy. The present study examined the effect of rosuvastatin (Ros) on key morphometric measures of renal injury and corresponding gene expression correlates following neonatal UUO in the rat. Methods: Neonatal rats subjected to UUO and controls were treated daily with vehicle or Ros for 14 days. Quantification of tubular dilatation, glomerular size and number and tubulointerstitial fibrotic area was performed and changes validated by reference to appropriate renal gene expression correlates. Results: UUO increased tubular diameter and interstitial fibrosis by 2.7- and 7-fold, respectively, in parallel with increases in renal transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) mRNA levels. Glomerular number and size were reduced by 52 and 33%, respectively. Reductions in WT-1 mRNA and protein expression were noted following obstruction occurring in tandem with reduced mRNA levels for BMP-7 and E-cadherin. Ros attenuated tubular dilatation (33%) and interstitial fibrosis (72%) in association with the normalization of renal TGF-β1 and TNF-α mRNA levels. Ros improved glomerular number and size (30 and 50%), and preserved mRNA and protein expression levels of WT-1 and normalized mRNA levels for BMP-7 and E-cadherin. Conclusions: Ros treatment attenuated all changes, most notably the increase in interstitial fibrosis. Notably, Ros treatment was unable to completely salvage glomerular development. Together these data highlight the therapeutic potential and limitations of Ros in neonatal obstruction.

© 2011 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: September 20, 2011
Accepted: November 08, 2011
Published online: December 29, 2011
Issue release date: February 2012

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 1

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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