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Jørgen Frøkiær

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

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  • Eun Hui Bae, Denmark
  • JongUn Lee, Denmark
  • Seong Kwon Ma, Denmark
  • In Jin Kim, Denmark
  • Jørgen Frøkiær
  • Søren Nielsen, Denmark
  • Sun Young Kim, Denmark
  • Soo Wan Kim, Denmark
  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
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.
Original languageEnglish
JournalNephrology, Dialysis, Transplantation
Volume24
Issue9
Pages (from-to)2692-700
Number of pages8
ISSN0931-0509
DOIs
Publication statusPublished - 2009

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