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NDT Advance Access published online on April 17, 2009

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp176
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



{alpha}-Lipoic acid prevents cisplatin-induced acute kidney injury in rats

Eun Hui Bae1,3, JongUn Lee2, Seong Kwon Ma1,3, In Jin Kim2,3, Jørgen Frøkiær4, Søren Nielsen4, Sun Young Kim5 and Soo Wan Kim1,3

1 Department of Internal Medicine 2 Department of Physiology, Chonnam National University Medical School 3 Cardiovascular Research Institute of Chonnam National University, Gwangju 501-757, Korea 4 The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark 5 Department of Physiology, Chonbuk National University Medical School, Jeonju 560-180, Korea

Correspondence and offprint requests to: Soo Wan Kim; E-mail: skimw{at}chonnam.ac.kr



  Abstract

Background. Cisplatin-induced nephropathy has been related to increased lipid peroxide formation and decreased activity of antioxidant enzymes in the kidney. The present study aimed to examine whether treatment with {alpha}-lipoic acid ({alpha}-LA) prevents the cisplatin-induced nephrotoxicity.

Methods. Two groups of rats were treated with cisplatin, one of which being cotreated with {alpha}-LA. The control group was treated with vehicle only. Four days later, the expression of aquaporins and sodium transporters was determined in the kidney by immunoblotting and immunohistochemistry. The arginine vasopressin-stimulated generation of cAMP was measured by radioimmunoassay. The expression of nitric oxide synthases (NOS) was determined by immunoblotting. The mRNA expression of endothelin-1 (ET-1) and tumour necrosis factor (TNF)-{alpha} was measured by real-time PCR. Apoptosis was examined by TUNEL staining.

Results. Following the treatment with cisplatin, urinary volume and fractional excretion of sodium increased. Accordingly, the expression of aquaporins 1–3, Na,K-ATPase, NHE3 and NKCC2 was decreased. The expression of adenylyl cyclase VI and vasopressin-stimulated cAMP generation was decreased. The expression of inducible NOS was increased, while that of endothelial NOS decreased. The ET-1 expression was increased. TUNEL-positive cells were increased, in association with an increased expression of TNF-{alpha}. {alpha}-LA treatment prevented dysregulation of these parameters and resumed the renal function.

Conclusion. {alpha}-LA may prevent the cisplatin-induced nephrotoxicity, possibly through preserving the activities of NO and ET systems and inhibiting the development of apoptosis.

Keywords: aquaporins; cisplatin; nitric oxide; sodium transporters; {alpha}-lipoic acid

Received for publication: 23.11.08
Accepted in revised form: 25. 3.09


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