Abstract
BackgroundReactive 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.MethodsMale 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.ResultsRadioactivity 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.ConclusionsThe 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.
Highlights
Reactive oxygen species (ROS) have been implicated in cisplatin-induced nephrotoxicity
We previously investigated the capability of [3H]hydromethidine for detection of ROS generated by sodium nitroprusside (SNP) microinjection into the striatum of mice, and the findings suggested that [3H]hydromethidine was rapidly distributed to the brain as well as peripheral organs, converted to its oxidized form through reaction with the ROS generated, and trapped in the tissue, while unreacted [3H]hydromethidine was immediately eliminated from normal tissue
Significantly high accumulation of radioactivity was observed in the corticomedullary junction of the kidney obtained from the cisplatin group at 10 or 18 h after cisplatin administration compared with the control group (10 h; 11.0 ± 0.8 (PSL − BG)/mm2, 18 h; 13.2 ± 1.8 (PSL − BG)/mm2)
Summary
Reactive oxygen species (ROS) have been implicated in cisplatin-induced nephrotoxicity. Techniques based on chemiluminescence [13,14,15] or fluorescence [16,17,18,19,20,21] from oxidizable molecular probes have been widely used for ROS detection in biological tissue samples or living animals. These optical imaging techniques employ a simple method with selectivity for a certain biological reaction, but there is a limitation when considering human studies and quantitative analysis due to signal attenuation with tissue depth
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