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NDT Advance Access published online on January 3, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk032
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordournals.org
Received April 19, 2005
Accepted December 7, 2005

Original Article

N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion

Nicoletta Nitescu 1 *, Sven-Erik Ricksten 1, Niels Marcussen 2, Börje Haraldsson 3, Ulf Nilsson 3, Samar Basu 4, and Gregor Guron 5

1 Department of Anaesthesiology and Intensive Care, Institute of Surgical Sciences, The Sahlgrenska Academy at Göteborg University, Sweden
2 University Institute of Pathology, Aarhus Kommunehospital, Denmark
3 Department of Nephrology, Institute of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Sweden
4 Section of Geriatrics and Clinical Nutrition, Department of Public Health and Caring Sciences, Faculty of Medicine, Uppsala University, Sweden
5 Department of Nephrology, Institute of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Sweden; Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy at Göteborg University, Sweden

* To whom correspondence should be addressed.
Nicoletta Nitescu, E-mail: nicoletta.nitescu{at}vgregion.se



  Abstract

Background. The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR).

Methods. Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2{alpha}), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR.

Results. Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2{alpha} excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2{alpha} excretion.

Conclusions. N-acetylcysteine improves kidney function, and reduces renal interstitial inflammation, in rats subjected to renal IR. These effects were associated with increased renal glutathione levels, and decreased plasma ascorbyl concentrations, suggesting that NAC attenuates renal and systemic oxidative stress in this model.

Keywords: acute renal failure; ischaemia reperfusion injury; lipid peroxidation; N-acetylcysteine; oxidative stress; reactive oxygen species.
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