title: Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation.
abstract: 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-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.
  
  
  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-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB 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- kappaB 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-kappaB activity.
authors.affiliation: Department of Internal Medicine and Renal Regeneration Laboratory, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000139:chemically induced* / Q000517:prevention & control*; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008063:Thioctic Acid; D002945:Cisplatin