期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 24, 期 10, 页码 3012-3020出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfp242
关键词
acute; cisplatin; inflammation; kidney injury; nuclear factor-kappa B
资金
- Ministry of Science&Technology (MoST)/Korea Science & Engineering Foundation (KOSEF) through the National Research Laboratory Program [ROA-2004-000-10292-0]
- Diabetes Research Center at Chonbuk National University [R13-2008-005-0000-0]
- Research funds from Chonbuk National University in 2007
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 (alpha-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-kappa B (NF-kappa B) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of alpha-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 alpha-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of alpha-LA on NF-kappa B activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappa 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 alpha-LA treatment. alpha-LA decreased the tissue levels of tumour necrosis factor-alpha, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. alpha-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF-kappa B p65 subunits in kidney tissue. Conclusions. These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappa B activity.
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