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钯(II)-二硫代氨基甲酸盐配合物的合成:大鼠体内生物学测定及肾毒性

Synthesis of a palladium(II)-dithiocarbamate complex: biological assay and nephrotoxicity in rats.

作者信息

Trevisan Andrea, Marzano Christine, Cristofori Patrizia, Borella Venturini Matteo, Giovagnini Lorena, Fregona Dolores

机构信息

Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.

出版信息

Arch Toxicol. 2002 Jun;76(5-6):262-8. doi: 10.1007/s00204-002-0329-7. Epub 2002 Apr 11.

Abstract

A new palladium(II)-dithiocarbamate complex, Pd(ESDT)Cl, was synthesised and its chemical characteristics are discussed. This complex was examined for its cytotoxic properties in human tumour cell lines; for comparison, the cytotoxicity of cisplatin was evaluated under the same experimental conditions. In particular, Pd(II)-complex cytotoxicity on ovarian carcinoma C13 cells, resistant to cisplatin, showed that there seemed to be no cross-resistance between Pd(ESDT)Cl and cisplatin. The effects on the kidney were also studied. Biochemical investigation on urinary parameters showed that the effects after a single injection are similar to those of cisplatin, with an increase of urinary proteins and enzyme excretion in urine, and a significant decrease of glutamine synthetase activity in the renal tissue. In addition, the Pd(II)-complex caused a significant decrease of p-aminohippuric acid uptake in renal cortical slices relative to cisplatin. On the other hand, histopathological findings showed that the effects of the Pd(II)-complex are more severe and diffuse than the damage caused by cisplatin. Biochemical and histopathological findings show that the Pd(II)-complex affects the pars recta and pars convoluta, in contrast to cisplatin, which only affects the pars recta.

摘要

合成了一种新型钯(II)-二硫代氨基甲酸盐配合物[Pd(ESDT)Cl]ₙ,并讨论了其化学特性。研究了该配合物在人肿瘤细胞系中的细胞毒性;作为比较,在相同实验条件下评估了顺铂的细胞毒性。特别是,对顺铂耐药的卵巢癌C13细胞的钯(II)配合物细胞毒性表明,[Pd(ESDT)Cl]ₙ与顺铂之间似乎不存在交叉耐药性。还研究了其对肾脏的影响。对尿液参数的生化研究表明,单次注射后的影响与顺铂相似,尿液中蛋白质和酶排泄增加,肾组织中谷氨酰胺合成酶活性显著降低。此外,相对于顺铂,钯(II)配合物导致肾皮质切片中对氨基马尿酸摄取显著降低。另一方面,组织病理学结果表明,钯(II)配合物的影响比顺铂造成的损伤更严重、更广泛。生化和组织病理学结果表明,与仅影响直部的顺铂不同,钯(II)配合物影响直部和曲部。

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