title: Rosiglitazone ameliorates cisplatin-induced renal injury in mice.
abstract: BACKGROUND
  Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Agonists of the peroxisome proliferator-activated receptor-gamma (PPARgamma), such as rosiglitazone, have been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to examine the protective effects of rosiglitazone on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection.
  
  
  METHODS
  Mice were treated with cisplatin with or without pre-treatment with rosiglitazone. Renal functions, histological findings, aquaporin 2 (AQP2) and adhesion molecule expression, macrophage infiltration and tumour necrosis factor-alpha (TNF-alpha) levels were investigated. The effect of rosiglitazone on nuclear factor (NF)-kappaB activity and on viability was examined using cultured human kidney (HK-2) cells.
  
  
  RESULTS
  Rosiglitazone significantly decreased both the damage to renal function and histological pathology after cisplatin injection. Pre-treatment with rosiglitazone reduced the systemic levels of TNF-alpha and down-regulated adhesion molecule expression in addition to the infiltration of inflammatory cells after cisplatin administration. Rosiglitazone restored the decreased AQP2 expression after cisplatin treatment. Pre-treatment with rosiglitazone blocked the phosphorylation of the p65 subunit of NF-kappaB in cultured HK-2 cells. Rosiglitazone had a protective effect via a PPARgamma-dependent pathway in cisplatin-treated HK-2 cells.
  
  
  CONCLUSIONS
  These results showed that pre-treatment with rosiglitazone attenuates cisplatin-induced renal damage through the suppression of TNF-alpha overproduction and NF-kappaB activation.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, 634-18 Keum-Am Dong, Jeonju 561-712, Republic of Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Sang-Ok
authors.initials: SO
authors.lastname: Moon
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Yong Bum
authors.initials: YB
authors.lastname: Jang
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002460:Cell Line / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005910:Glioma / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000378:metabolism; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002096:C-Peptide; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; C498144:Rela protein, mouse; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D000077288:Troglitazone; D002945:Cisplatin; D015230:Prostaglandin D2; C039671:ciglitazone