Cytochemical research concerning the protective effect of methylprednisolone against cisplatin-induced nephrotoxicity

甲泼尼龙对顺铂肾毒性保护作用的细胞化学研究

• 批准号: 05671323
• 负责人: UOZUMI Jiro
• 金额: $ 1.22万
• 依托单位: Kyshu University , Faculty of Medicine, Department of Urology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671323/
• 关键词: Cisplatin; Methylpredonisolone; Nephrotoxicity; Renal Protection; 予防

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 … More 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

顺铂是一种有效的抗肿瘤药物，但它具有肾毒性的副作用。本文研究了甲基强的松龙（MP）对顺铂肾毒性的拮抗作用及其机制。顺铂6.5mg/kg静脉注射联合不同剂量的MP皮下注射。在第5天，用MP4或顺铂注射前2小时预处理的大鼠的BUN和血清肌酐水平显著低于仅接受顺铂的大鼠。为了评价MP对顺铂肾毒性保护作用的机制，研究了MP对顺铂静脉给药后体内铂动力学的影响。在大鼠中注射顺铂后，MP增加尿铂排泄，同时伴有血浆和肾脏铂浓度降低。MP体内预处理对顺铂诱导的对氨基马尿酸减少的影响（P ...更多信息 AH）积累和再生利用大鼠肾皮质切片进行了检查。在体外孵育后，用2 mM顺铂制备的大鼠肾切片中的PAH蓄积显著降低，其程度与对照大鼠制备的切片中观察到的程度相同。然而，顺铂的抑制作用明显低于对照组大鼠脑片。这些结果表明，MP可能有助于其对顺铂肾毒性的保护作用，通过在肾上皮细胞的凋亡过程。临床研究证实MP对顺铂肾毒性的保护作用。14例尿路上皮肿瘤患者根据MVAC方案注射顺铂。在化疗的第一个疗程中不给予MP以提供对照，但在每例患者的化疗的第二个疗程中，在顺铂之前2-3小时给予2，000 mg/体的剂量。MP对顺铂注射后尿酶排泄或血清肌酐水平的升高无明显抑制作用。然而，在MP预处理期间顺铂输注后Ccr的降低显著低于对照组。MP对顺铂肾毒性的保护作用也在这项前瞻性临床研究中显示。MP被认为是一种有效的抗顺铂肾毒性药物。少

项目成果

Uozumi J: "Protective effect of methylprednisolone against cisplatin nephrotoxicity" Jpn J Urol in Japanses. 86. 44-46 (1995)

Uozumi J：“甲泼尼龙对顺铂肾毒性的保护作用”Jpn J Urol 日本人。

J.Uozumi: "Methylprednisolone reduces cisplatin nephrotoxicity." J Pharmaco-bio dynamics. 15. 693-697 (1992)

J.Uozumi：“甲基强的松龙可降低顺铂的肾毒性。”

J.Uozumi: "Platinum accumulation in the kidney and liver following chemotherpy with cisplatin in humans" Int.Urol.Nephrol.25. 215-220 (1993)

J.Uozumi：“人类顺铂化疗后肾脏和肝脏中铂的积累”Int.Urol.Nephrol.25。

Uozumi J: "Platinum accumulation in the kidney and changes in creatinine clearance following chemotherapy with cisplatin in humans" Urol Int. 51. 57-61 (1993)

Uozumi J：“人体顺铂化疗后肾脏中铂的积累和肌酐清除率的变化”Urol Int。

鯉川弥須宏: "Cisplatin腎毒性に対するmethylprednisoloneの予防効果に関する研究" 福岡医誌. 86. 31-39 (1995)

Yasu Hiroshi Koikawa：“甲基泼尼松龙对顺铂肾毒性的预防作用的研究”福冈医学杂志 86. 31-39 (1995)。