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

基本信息

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

项目摘要

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，但它具有肾毒性的不利作用。在本研究中，甲基 - 蛋白酶酮（MP）对顺铂诱导的肾毒性及其机制的预防作用是研究的。将大鼠静脉注射6.5 mg/kg的顺铂与皮下MP组合以各种剂量在变化的时机下。在顺铂注射前预处理MP4或2小时预处理的大鼠中的BUN和血清肌酐水平明显低于单独接受顺铂的大鼠。评估负责MP对方顺铂的保护作用的机制。 MP增加了铂铂的增加是由于在大鼠中顺铂注射后血浆和肾铂浓度的降低而发生。使用MP的体内预处理对顺铂诱导的P-氨基磷酸盐（P…更多AH）积累和糖异生的影响，使用由大鼠制备的肾皮质切片进行了检查。在与2mm顺铂孵育后，制备大鼠制备大鼠的PAH积累显着降低，其程度等于从对照大鼠制备的切片中观察到的。但是，顺铂对对照大鼠的切片中的抑制作用明显少于切片中的抑制作用。这些发现表明，MP可能通过肾上皮细胞的谷杆菌生成过程来促进其针对顺铂肾毒性的保护作用。进行了临床研究以确认MP对顺铂肾毒性的受保护作用。根据MVAC治疗，有14例尿路上皮肿瘤患者用顺铂注射。在化学疗法的第一个过程中，未施用MP来提供对照，但在顺铂前2-3小时以2,000 mg/身体的剂量给予每个患者的化学疗法。在顺铂注射后，MP没有显着抑制尿酶极端或血清肌酐水平的升高。但是，在MP预处理周期中排顺铂输注后CCR的减少显着低于对照中观察到的。在这项前瞻性临床研究中，还指出了MP对顺铂肾毒性的受保护作用。 MP被认为是针对顺铂肾毒性的有用药物。较少的