Kang Kyung Pyo, Kim Duk Hoon, Jung Yu Jin, Lee Ae Sin, Lee Sik, Lee Sang Yong, Jang Kyu Yun, Sung Mi Jeong, Park Sung Kwang, Kim Won
Department of Internal Medicine and Renal Regeneration Laboratory, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Nephrol Dial Transplant. 2009 Oct;24(10):3012-20. doi: 10.1093/ndt/gfp242. Epub 2009 May 27.
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-kappaB (NF-kappaB) 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.
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-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB p65 subunits in kidney tissue.
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- kappaB p65 subunits in kidney tissue.
These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity.
顺铂是一种用于治疗恶性肿瘤的化疗药物。然而，顺铂会产生多种副作用，如肾毒性、神经毒性、致吐作用和耳毒性。炎症是顺铂肾毒性的重要机制。α-硫辛酸（α-LA）具有抗炎作用，可通过抑制核因子-κB（NF-κB）信号通路来抑制人内皮细胞中黏附分子的表达以及单核细胞黏附。本研究的目的是探讨α-LA在顺铂诱导的肾损伤中的抗炎作用，并研究其保护机制。
给C57BL/6小鼠注射顺铂（20mg/kg），同时或不同时给予α-LA治疗（100mg/kg，连续3天）。检测肾功能、组织学变化、黏附分子表达和炎性细胞浸润情况。通过检测肾组织中NF-κB p65亚基的核转位和磷酸化来评估α-LA对NF-κB活性的影响。
用尿素氮、血清肌酐水平和肾小管损伤评分衡量肾功能，顺铂诱导的肾功能下降在α-LA治疗后得到缓解。α-LA降低了肿瘤坏死因子-α的组织水平、细胞间黏附分子-1（ICAM-１）和单核细胞趋化蛋白-1（MCP-1）的表达，并抑制了CD11b阳性巨噬细胞的浸润。α-LA还减弱了顺铂诱导的肾组织中NF-κB p65亚基磷酸化和核转位的增加。
这些结果表明，α-LA治疗可通过降低炎性黏附分子表达和NF-κB活性来改善顺铂诱导的急性肾损伤。
