The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin-induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the groups treated with the combination of nedaplatin and FOM as compared with the nedaplatin-alone group. The concentration of nedaplatin was significantly lower in the renal cortex of rats treated with the combination of nedaplatin and FOM as compared with those treated with nedaplatin alone (p < 0.05). In conclusion, the concomitant administration of FOM and nedaplatin may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of nedaplatin.
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Comparative analysis of gene expression between renal cortex and papilla in nedaplatin-induced nephrotoxicity in rats.
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Developmental Research Laboratories, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
To elucidate the mechanism of nephrotoxicity caused by anti-neoplastic platinum complex, nedaplatin (NDP), treatment with a particular focus on the renal papillary toxicity, we analysed the gene expression profiles of two renal regions, the cortex (RC) and the papilla (RP) in rat kidneys. Male Wistar rats received a single administration of 10 mg/kg intravenous NDP or vehicle alone (5% xylitol solution) and were sacrificed six days later. The kidneys were dissected into the RC and RP and used for histopathological and microarray analyses.
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Developmental Research Laboratories, Shionogi & Co., Ltd, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Nedaplatin (NDP) is a second-generation antineoplastic platinum complex, with reduced nephrotoxicity. Two experiments were conducted to characterize the time course of changes of its nephrotoxicity and to further evaluate whether hydration is useful for amelioration of nephrotoxicity. In the first experiment, 8-week-old male rats treated with 6 or 9 mg kg(-1) NDP at a single intravenous dose were killed 2, 4, 7 and 14 days after dosing.
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Division of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation.
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J Infect Chemother
February 2005
Division of Clinical Pharmacy, Kyoritsu University of Pharmacy, 1-15-30 Shibakoen, Minato-ku, 105-8512, Tokyo, Japan.
The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin-induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the groups treated with the combination of nedaplatin and FOM as compared with the nedaplatin-alone group.
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