title: Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis.
abstract: BACKGROUND
  Cisplatin chemotherapy often causes acute kidney injury in cancer patients. The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation, activation of p53 tumour suppressor protein and tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic activities. The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism.
  
  
  METHODS
  C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without treatment with luteolin (50 mg/kg for 3 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of luteolin on cisplatin-induced expression of renal p53, PUMA-α and Bcl-2 family proteins were evaluated.
  
  
  RESULTS
  Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction, reducing tubular cell damage, oxidative stress and apoptosis. Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA-α, Bax and caspase-3 activity that were significantly decreased by treatment with luteolin.
  
  
  CONCLUSIONS
  These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney.
authors.affiliation: Department of Internal Medicine and Renal Regeneration Laboratory, Research Institute of Clinical Medicine and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kunka Mohanram
authors.initials: KM
authors.lastname: Ramkumar
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Moon Hyang
authors.initials: MH
authors.lastname: Park
authors.forename: Si-Gyun
authors.initials: SG
authors.lastname: Roh
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D047311:Luteolin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D047311:Luteolin; D002945:Cisplatin