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NDT Advance Access published online on May 9, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn237
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© The Author [2008]. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org


N-acetylcysteine protects against renal injury following bilateral ureteral obstruction

Maria Heloisa Massola Shimizu1, Alexandre Danilovic2, Lucia Andrade1, Rildo A. Volpini1, Alexandre B. Libório1, Talita R.C. Sanches1 and Antonio Carlos Seguro1

1 Department of Nephrology 2 Department of Urology, University of São Paulo School of Medicine, São Paulo, Brazil

Correspondence and offprint requests to: Antonio Seguro, Laboratorio Pesquisa Basica LIM/12, Faculdade de Medicina USP, Av. Dr. Arnaldo, 455 3° andar, sala 3310, CEP 01246-000 São Paulo, Brazil. Tel/Fax: +55-11-3088-2267; E-mail: trulu{at}usp.br, luciacan{at}usp.br



  Abstract

Background. Obstructive nephropathy decreases renal blood flow (RBF) and glomerular filtration rate (GFR), causing tubular abnormalities, such as urinary concentrating defect, as well as increasing oxidative stress. This study aimed to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on the protein expression of aquaporin 2 (AQP2) and endothelial nitric oxide synthase (eNOS), after the relief of bilateral ureteral obstruction (BUO).

Methods. Adult male Wistar rats were divided into four groups: sham (sham operated); sham operated + 440 mg/kg body weight (BW) of NAC daily in drinking water, started 2 days before and maintained until 48 h after the surgery; BUO (24-h BUO only); BUO + NAC-pre (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started 2 days before BUO); and BUO + NAC-post (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started on the day of BUO relief). Experiments were conducted 48 h after BUO relief.

Results. Serum levels of thiobarbituric reactive substances, which are markers of lipid peroxidation, were significantly lower in NAC-treated rats than in the BUO group rats. The administration of NAC provided significant protection against post-BUO GFR drops and reductions in RBF. Renal cortices and BUO rats presented decreased eNOS protein expression of eNOS in the renal cortex of BUO group rats, whereas it was partially recovered in BUO + NAC-pre group rats. Urine osmolality was significantly lower in BUO rats than in sham group rats or NAC-treated rats, the last also presenting less interstitial fibrosis. Post-BUO downregulation of AQP2 protein expression was averted in the BUO + NAC-pre group rats.

Conclusions. This study demonstrates that NAC administration ameliorates the renal function impairment observed 48 h after the relief of 24-h BUO. Oxidative stress is important for the suppression of GFR, RBF, tissue AQP2 and eNOS in the polyuric phase after the release of BUO.

Keywords: aquaporin 2; bilateral ureteral obstruction; endothelial nitric oxide synthase; inulin clearance; N-acetylcysteine

Received for publication: 11. 1.08
Accepted in revised form: 7. 4.08


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