Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity

Nozomi Takai, Kohji Abe, Misato Tonomura, Natsumi Imamoto, Kazumi Fukumoto, Miwa Ito, Sotaro Momosaki, Kae Fujisawa, Kenji Morimoto, Nobuo Takasu, Osamu Inoue

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]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 [3H]hydromethidine injection. Results: Radioactivity accumulation after [3H]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 [3H]hydromethidine was rapidly distributed to the kidney after its injection and trapped there in the presence of ROS such as hydroxyl radicals, suggesting that [3H]hydromethidine is useful for assessment of the renal ROS amount in cisplatin-induced nephrotoxicity.

Original languageEnglish
Article number38
JournalEJNMMI Research
Volume5
Issue number1
DOIs
Publication statusPublished - Dec 23 2015
Externally publishedYes

Keywords

  • Cisplatin
  • Hydroxyl radical
  • Nephrotoxicity
  • Reactive oxygen species

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Imaging of reactive oxygen species using [<sup>3</sup>H]hydromethidine in mice with cisplatin-induced nephrotoxicity'. Together they form a unique fingerprint.

Cite this