Stĕtinová V, Trejtnar F, Kopecký J, Grossmann V, Kvètina J, Kopecká L, Semecký V
Institute of Experimental Biopharmaceutics, Joint Laboratories of the Academy of Sciences of the Czech Republic, Hradec Králové, Czech Republic.
J Pharmacol Toxicol Methods. 1996 Dec;36(4):199-204. doi: 10.1016/s1056-8719(96)00126-8.
The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1 mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted epithelial cells, was examined. Repeated administration of cyclosporin A (45 and 56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted epithelial cells. The degree of excretion of epithelial cells after administration of both drugs was compared with the urinary excretion of alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, which indicated nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than the increase in the excretion of epithelial cells. In the experiment with cyclosporin A, urinary excretion of epithelial cells was further correlated with renal functional tests (clearance of polyfructosan and hippurate.
肾小管上皮细胞每分钟排泄量的测定方法,使得通过毒素的肾毒性作用过程进行研究成为可能,毒素会使肾小管圆形上皮细胞排泄量增加。研究了重复静脉注射两性霉素B(1mg/kg)的肾毒性作用,其可使排泄上皮细胞数量增加达12倍。重复口服环孢素A(45mg/kg和56mg/kg)可使排泄上皮细胞数量增加达23倍。将两种药物给药后上皮细胞的排泄程度与丙氨酸氨基肽酶和N-乙酰-β-D-氨基葡萄糖苷酶的尿排泄量进行比较,结果表明两性霉素B和环孢素A具有肾毒性,但敏感性低于上皮细胞排泄量的增加。在环孢素A的实验中,上皮细胞的尿排泄量进一步与肾功能测试(聚果糖和马尿酸盐清除率)相关。