Amelioration of Nedaplatin-Induced Nephrotoxicity by Continuous Infusion in Rats

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The current experiment was conducted to evaluate whether prolongation of infusion time is useful for the amelioration of nedaplatin (NDP)-induced nephrotoxicity. Eight-week-old male rats were treated with 12 mg/kg NDP with the following dosing protocols, bolus injection, 1- or 4-hour continuous infusions (1hIF or 4hIF, respectively), and sacrificed 3 days after dosing. Urinary parameters were monitored on the day of the sacrifice, and the kidneys and femurs were removed for histopathological examination and bone marrow analysis. In the Bolus-NDP group, urine pH and specific gravity were decreased compared with the corresponding control group and glucosuria and occult blood were detected, while no abnormalities were noted in these urine parameters in the 4hIF-NDP group. Histopathological examination revealed slight to moderate renal lesions, such as single cell and/or focal necrosis in the epithelium of cortical tubules and collecting ducts in the renal papilla in the Bolus-NDP group. In the 1hIF- and 4hIF-NDP groups, there were clear reductions in the severity of renal tubular damage compared with the Bolus-NDP group, and the severity of renal tubular damage tended to reduce with increased infusion time. A TUNEL assay revealed that the numbers of TUNEL-positive cells in the 1hIF- and 4hIF-NDP groups were significantly lower than that in the Bolus-NDP group. There was a significant decrease in the number of TUNEL-positive cells in the 4hIF-NDP group compared with that in the 1hIF-NDP group. However, prolongation of the infusion time had no clear effect on the myelotoxicity of NDP. These results provide new evidence that prolongation of the infusion time is effective at minimizing the nephrotoxicity of NDP.
日本毒性病理学会の論文
2007-09-30

Amelioration of Nedaplatin-Induced Nephrotoxicity by Continuous Infusion in Rats

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