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[顺-二氨-1,1-环丁烷二羧酸铂II对大鼠肾毒性的研究——特别提及形态学变化]

[Study on nephrotoxicity in rats receiving cis-diammine-1,1-cyclobutane dicarboxylate platinum II--special reference to morphological changes].

作者信息

Kimura S, Nakajima Y, Hasegawa S, Tazaki H

出版信息

Nihon Hinyokika Gakkai Zasshi. 1989 Apr;80(4):517-25. doi: 10.5980/jpnjurol1989.80.517.

Abstract

Nephrotoxic effects of cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA) were investigated in male 6 weeks old Wistar rats. The animals were divided into 4 groups: Group I (each received a single intraperitoneal injection of CBDCA 80, 120 mg/kg); Group II (a single intraperitoneal injection of CBDCA 80, 120 mg/kg after withdrawal of food and water for 2 days); Group III (intravenous administration of CBDCA 15, 30 mg/kg for 7 consecutive days after withdrawal of food and water for 2 days); Group IV (controls). Rats from each group were sacrificed at 3, 7, 10 and 14 days following the start of the experiment. Serum levels of BUN and creatinine were then measured and renal histopathological examination was conducted by light and electron microscopy. In addition, the total platinum concentration in the serum was measured in Group I, and X-ray microanalysis was performed after intraperitoneal administration of CBDCA (100 mg/kg) and cis-Diamminedichloroplatinum (II) (CDDP) (6 mg/kg) for 2 consecutive days (Group V). The results showed increased levels of BUN in each group due to catabolism. No significant increase in serum creatinine was observed and there appeared to be no evidence of renal dysfunction. For all groups, localized vacuolar degeneration in the epithelial cells of the tubules was predominantly apparent. Electron microscopy revealed only degeneration of the epithelium mainly in the proximal tubules and also showed reabsorption of platinum from the lumen of the tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

研究了顺式二胺-1,1-环丁烷二羧酸铂II(CBDCA)对6周龄雄性Wistar大鼠的肾毒性作用。将动物分为4组:第一组(每组腹腔注射一次80、120mg/kg的CBDCA);第二组(禁食禁水2天后腹腔注射一次80、120mg/kg的CBDCA);第三组(禁食禁水2天后连续7天静脉注射15、30mg/kg的CBDCA);第四组(对照组)。每组大鼠在实验开始后的3、7、10和14天处死。然后测量血清尿素氮和肌酐水平,并通过光学和电子显微镜进行肾脏组织病理学检查。此外,测量了第一组血清中的总铂浓度,并在连续2天腹腔注射CBDCA(100mg/kg)和顺式二氯二氨铂(II)(CDDP)(6mg/kg)后进行了X射线微分析(第五组)。结果显示,由于分解代谢,每组的尿素氮水平均升高。未观察到血清肌酐有显著升高,似乎也没有肾功能障碍的证据。对于所有组,肾小管上皮细胞的局部空泡变性主要很明显。电子显微镜检查仅显示主要在近端小管的上皮细胞变性,并且还显示从肾小管腔中重吸收了铂。(摘要截断于250字)

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