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[硒对顺二氯二氨铂(CDDP)所致小鼠肾毒性的保护作用研究]

[Studies on protective effect of selenium on the nephrotoxicity of cis-diamminedichloroplatinum (CDDP) in mice].

作者信息

Araya Y

机构信息

First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.

出版信息

Hokkaido Igaku Zasshi. 1990 May;65(3):245-53.

PMID:2165995
Abstract

Protective effect of sodium selenite (Se) on the nephrotoxicity of cis-diamminedichloroplatinum (CDDP) was studied in mice. The administration of CDDP alone at doses of 50 mumols/kg caused the increase of blood urea nitrogen (BUN) and urinary N-acetylglucosaminidase (NAG) and the degeneration of proximal tubule cells pathologically. The co-administration of Se, especially at doses of 20 mumols/kg/day, inhibited the increase of BUN and urinary NAG and depressed the degeneration of proximal tubule cells. The administration of CDDP at doses of 20 mumols/kg caused a mild reduction of transplanted Lewis lung carcinoma and a decrease of metastasis to lung. The co-administration of Se at doses of 8 mumols/kg didn't inhibit the antitumor effect of CDDP against Lewis lung carcinoma. Co-administration of Se didn't influence concentration of CDDP in plasma, blood cells, kidney and liver. In mice fed Se deficient diet, the nephrotoxicity of CDDP increased and activities of glutathione peroxidase (G-Px) in blood and kidney decreased. In mice co-administered with Se, G-Px activities didn't increase. These results suggest that co-administration of Se may allow use of CDDP at higher doses in cancer chemotherapy. Interaction between CDDP and Se differs from that between mercury and Se, and cadmium and Se(formation of compound). Intake of Se is related to appearance of the nephrotoxicity of CDDP. G-Px may be related to a part of the protective effect of Se on the nephrotoxicity of CDDP.

摘要

研究了亚硒酸钠(Se)对顺二氨二氯铂(CDDP)肾毒性的保护作用。单独给予剂量为50μmol/kg的CDDP会导致血尿素氮(BUN)升高、尿N-乙酰氨基葡萄糖苷酶(NAG)升高,并且近端小管细胞出现病理性退变。同时给予Se,尤其是剂量为20μmol/kg/天,可抑制BUN和尿NAG的升高,并减轻近端小管细胞的退变。给予剂量为20μmol/kg的CDDP会使移植的Lewis肺癌轻度缩小,并减少肺转移。同时给予剂量为8μmol/kg的Se不会抑制CDDP对Lewis肺癌的抗肿瘤作用。同时给予Se不影响CDDP在血浆、血细胞、肾脏和肝脏中的浓度。在饲喂缺硒饮食的小鼠中,CDDP的肾毒性增加,血液和肾脏中的谷胱甘肽过氧化物酶(G-Px)活性降低。在同时给予Se的小鼠中,G-Px活性并未增加。这些结果表明,同时给予Se可能允许在癌症化疗中使用更高剂量的CDDP。CDDP与Se之间的相互作用不同于汞与Se以及镉与Se之间的相互作用(形成化合物)。硒的摄入与CDDP肾毒性的出现有关。G-Px可能与Se对CDDP肾毒性的部分保护作用有关。

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