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Nephrol Dial Transplant. 2009 Sep;24(9):2692-700. doi: 10.1093/ndt/gfp176. Epub 2009 Apr 17.

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

Author information

1
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

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.

PMID:
19376830
DOI:
10.1093/ndt/gfp176
[Indexed for MEDLINE]

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