NDT Advance Access originally published online on May 27, 2009
Nephrology Dialysis Transplantation 2009 24(10):3012-3020; doi:10.1093/ndt/gfp242
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Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation
1 Department of Internal Medicine and Renal Regeneration Laboratory 2 Department of Radiology 3 Department of Pathology, Research Institute of Clinical Medicine and Diabetic Research Center, Chonbuk National University Medical School, Jeonju 4 Food Function Research Center, Korea Food Research Institute, Seongnam, Gyeongki, Republic of Korea
Correspondence and offprint requests to: Won Kim; E-mail: kwon{at}chonbuk.ac.kr
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Abstract |
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Background. Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (
-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-
B (NF-B) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of -LA during cisplatin-induced renal injury and to examine the mechanisms of protection.
Methods. C57BL/6 mice were given cisplatin (20 mg/kg) with or without -LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of -LA on NF-B activity was evaluated by examining nuclear translocation and phosphorylation of NF-B p65 subunits in kidney tissue.
Results. Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by -LA treatment. -LA decreased the tissue levels of tumour necrosis factor-, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. -LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- B p65 subunits in kidney tissue.
Conclusions. These results suggest that -LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-B activity.
Keywords: acute; cisplatin; inflammation; kidney injury; nuclear factor-B
* These authors contributed equally to this work.
Received for publication: 15.10.08
Accepted in revised form: 29. 4.09