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

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

Research output: Contribution to journalArticle

6 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

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Cisplatin
Reactive Oxygen Species
Kidney
Blood Urea Nitrogen
Hydroxyl Radical
Lipid Peroxidation
Injections
Creatinine
N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine
Malondialdehyde
Serum
Radioactivity

Keywords

  • Cisplatin
  • Hydroxyl radical
  • Nephrotoxicity
  • Reactive oxygen species

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity. / Takai, Nozomi; Abe, Koji; Tonomura, Misato; Imamoto, Natsumi; Fukumoto, Kazumi; Ito, Miwa; Momosaki, Sotaro; Fujisawa, Kae; Morimoto, Kenji; Takasu, Nobuo; Inoue, Osamu.

In: EJNMMI Research, Vol. 5, No. 1, 38, 23.12.2015.

Research output: Contribution to journalArticle

Takai, N, Abe, K, Tonomura, M, Imamoto, N, Fukumoto, K, Ito, M, Momosaki, S, Fujisawa, K, Morimoto, K, Takasu, N & Inoue, O 2015, 'Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity', EJNMMI Research, vol. 5, no. 1, 38. https://doi.org/10.1186/s13550-015-0116-0
Takai, Nozomi ; Abe, Koji ; Tonomura, Misato ; Imamoto, Natsumi ; Fukumoto, Kazumi ; Ito, Miwa ; Momosaki, Sotaro ; Fujisawa, Kae ; Morimoto, Kenji ; Takasu, Nobuo ; Inoue, Osamu. / Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity. In: EJNMMI Research. 2015 ; Vol. 5, No. 1.
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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.",
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AU - Takai, Nozomi

AU - Abe, Koji

AU - Tonomura, Misato

AU - Imamoto, Natsumi

AU - Fukumoto, Kazumi

AU - Ito, Miwa

AU - Momosaki, Sotaro

AU - Fujisawa, Kae

AU - Morimoto, Kenji

AU - Takasu, Nobuo

AU - Inoue, Osamu

PY - 2015/12/23

Y1 - 2015/12/23

N2 - 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.

AB - 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.

KW - Cisplatin

KW - Hydroxyl radical

KW - Nephrotoxicity

KW - Reactive oxygen species

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