Batzer M A, Aggarwal S K
Cancer Chemother Pharmacol. 1986;17(3):209-17. doi: 10.1007/BF00256686.
Isolated rat kidney tubules were cultured in Earle's medium with and without the platinum coordination complexes. Aliquots were taken at 0, 1, 2, 3, 4, 5, 6, and 8 h and analyzed for the amount of Na+/K+-ATPase, Ca2+-ATPase, alkaline phosphatase, and acid phosphatase. Culture medium was also analyzed biochemically for the amounts of alkaline phosphatase present. There is a decrease in the various enzymes levels of the tubules after incubation in nephrotoxic analogues with a corresponding increase in the culture medium. These results compare favorably with in vivo studies. The alkaline phosphatase monitored in the rat kidney cross sections from both the normal and the drug-treated animals at 0, 3, 5, 10, and 20 days showed a correlation in the decrease of enzyme levels in the kidney with a corresponding increase in the urinary levels in both the Wistar and the Long Evans rats. The baseline levels were higher in the Long Evans rats than in the Wistar rats. After cisplatin (nephrotoxic) treatment the Long Evans rats had twice as much alkaline phosphatase in the urine at day 5 as the Wistar rats. Rats treated with cyclobutanedicarboxylatoplatinum (II) did have some alkaline phosphatase output in the urine in excess of the normal levels, but this increase was not so highly significant as to justify classifying the drug as nephrotoxic.
将分离出的大鼠肾小管在含有和不含有铂配位化合物的Earle培养基中培养。在0、1、2、3、4、5、6和8小时时取出等分试样，分析其中Na+/K+-ATP酶、Ca2+-ATP酶、碱性磷酸酶和酸性磷酸酶的含量。还对培养基中的碱性磷酸酶含量进行生化分析。在用具有肾毒性的类似物孵育后，肾小管中各种酶的水平降低，而培养基中的相应酶水平则升高。这些结果与体内研究结果相当吻合。在0、3、5、10和20天时，对正常和药物处理动物的大鼠肾脏横截面中的碱性磷酸酶进行监测，结果显示，在Wistar大鼠和Long Evans大鼠中，肾脏中酶水平的降低与尿液中相应酶水平的升高存在相关性。Long Evans大鼠的基线水平高于Wistar大鼠。顺铂（具有肾毒性）处理后，第5天时Long Evans大鼠尿液中的碱性磷酸酶含量是Wistar大鼠的两倍。用环丁烷二羧酸铂（II）处理的大鼠尿液中的碱性磷酸酶输出量确实超过正常水平，但这种增加并不显著，不足以将该药物归类为具有肾毒性。
