| Project/Area Number |
05671323
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Kyshu University , Faculty of Medicine, Department of Urology |
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Principal Investigator |
UOZUMI Jiro (1994-1995) Kyushu University, Faculty of Medicine, Department of Urology, Assistant Prof., 医学部, 講師 (30223514)
上田 豊史 (1993) 九州大学, 医学部, 助教授 (20037401)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUDA Noriaki Kyushu University, Faculty of Medicine, Department of Urology, Assistant Prof., 医学部, 助手 (20264038)
安増 哲生 九州大学, 医学部, 助手 (30166524)
〓住 二郎 九州大学, 医学部, 講師 (30223514)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Cisplatin / Methylpredonisolone / Nephrotoxicity / Renal Protection / 予防 |
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| Research Abstract |
cisplatin is an effective antitumor drug, but it is has an adverse effect of nephrotoxicity. In the present study, prophylatic effects of methyl-prednisolone (MP)on cisplatin-induced nephrotoxicity and its mechanism were studied. Rats were intravenously injected with 6.5 mg/kg of cisplatin combined with a subcutaneous MP in various doses at varous timing. BUN and serum creatinine levels in rats pretreated with MP4 or 2 hours prior to cisplatin injection were significantly lower than those in rats received cisplatin alone on day 5. To evaluate the mechanism responsible for the protective action of MP against cisplatin nephrotoxicity, the effects of MP on platinum kinetics following intraveenous administration of cisplatin in vivo were studied. MP increased urinary platinum excretion accompanied by a decrease in plasma and kidney platinum concentrations following cisplatin injections in rats. The effect of in vivo pretreatment with MP on cisplatin-induced reduction in p-aminohippurate (P
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AH) accumulation and gluconeogenesis was examined using renal cortical slices prepared from rats. The PAH accumulation in the kidney slices prepared rats were significantly reduced following in vitro incubation with 2mM cisplatin, to a degree equal to that observed in the slices prepared from control rats. However, the inhibitory effect of cisplatin on significantly less than that found in the slices from control rats. These findings suggest that MP may contribute to its protective effect against cisplatin nephrotoxicity via the process of gluconeogenesis in renal epithelial cells. The clinical study was conducted to confirm the protective effects of MP against the cisplatin nephrotoxicity. Fourteen patients with urothelial tumors werejinjected with cisplatin according to the MVAC therapy. MP was not administered during the first course of chemotherapy to provide a control, but was given in a dose of 2,000 mg/body 2-3 hours before cisplatin during the second course of chemotherapy in each patient. MP did not significantly inhibist the elevation in urinary enzyme excretion or serum creatinine levels following the cisplatin injection. However, the decrease in Ccr following cisplatin infusion in the MP-pretreated period were significantly lower than that observed in the control. The protective effects of MP against cisplatin nephrotoxicity were also indicated in this prospective clinical study. MP is considered to be a useful agent against cisplatin nephrotoxicity. Less
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