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 language | English |
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Article number | 38 |
Journal | EJNMMI Research |
Volume | 5 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 23 2015 |
Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity
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
UR - http://www.scopus.com/inward/record.url?scp=84937809374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937809374&partnerID=8YFLogxK
U2 - 10.1186/s13550-015-0116-0
DO - 10.1186/s13550-015-0116-0
M3 - Article
AN - SCOPUS:84937809374
VL - 5
JO - EJNMMI Research
JF - EJNMMI Research
SN - 2191-219X
IS - 1
M1 - 38
ER -