title: Imaging of reactive oxygen species using [(3)H]hydromethidine in mice with cisplatin-induced nephrotoxicity.
abstract: BACKGROUND
  Reactive oxygen species (ROS) have been implicated in cisplatin-induced nephrotoxicity. The aim of this study was to investigate the potential of using [(3)H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([(3)H]hydromethidine) for ex vivo imaging of regional ROS overproduction in mouse kidney induced by cisplatin.
  
  
  METHODS
  Male C57BL/6 J mice were intraperitoneally administered with a single dose of cisplatin (30 mg/kg). Renal function was assessed by measuring serum creatinine and blood urea nitrogen (BUN) levels and morphology by histological examination. Renal malondialdehyde levels were measured as a lipid peroxidation marker. Autoradiographic studies were performed with kidney sections from mice at 60 min after [(3)H]hydromethidine injection.
  
  
  RESULTS
  Radioactivity accumulation after [(3)H]hydromethidine injection was observed in the renal corticomedullary area of cisplatin-treated mice and was attenuated by pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger. Cisplatin administration significantly elevated serum creatinine and BUN levels, caused renal tissue damage, and promoted renal lipid peroxidation. These changes were significantly suppressed by DMTU pretreatment.
  
  
  CONCLUSIONS
  The present study showed that [(3)H]hydromethidine was rapidly distributed to the kidney after its injection and trapped there in the presence of ROS such as hydroxyl radicals, suggesting that [(3)H]hydromethidine is useful for assessment of the renal ROS amount in cisplatin-induced nephrotoxicity.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka, 561-0825, Japan, nozomi.takai@shionogi.co.jp.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takai
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
authors.forename: Misato
authors.initials: M
authors.lastname: Tonomura
authors.forename: Natsumi
authors.initials: N
authors.lastname: Imamoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Miwa
authors.initials: M
authors.lastname: Ito
authors.forename: Sotaro
authors.initials: S
authors.lastname: Momosaki
authors.forename: Kae
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Morimoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takasu
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue