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

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.