Wachsmuth E D, Wirz H
Curr Probl Clin Biochem. 1979(9):88-104.
Male rats were housed singly in metabolic cages, injected i.v. with cephaloridine, 24 h urine samples collected successively; then the rats were killed for obtaining the kidneys of corresponding animals. The concentrations of protein, aminopeptidase (AP), alkaline phosphatase (aPP), lactic dehydrogenase (LDH), and aldolase (ALD) were determined in urine and the percentages of injured proximal tubules counted in sections stained for aPP. The results from individual animals were: (1) After placing animals singly in metabolic cages large but not systematic changes of urinary enzyme concentrations occurred. After 6-10 days the enzymes reached steady state levels. (2) After a single injection of cephaloridine a dose dependent injury of proximal tubules was observed, the urinary LDH content correlating best with the tubular injury (r greater than 0.93) and giving up to 1,000 fold increases above normal values. (3) A circadian rhythm of the susceptibility of rat kidney for cephaloridine was observed, the smallest response was seen when the animals were injected at 7 a.m. and the largest after injection at 7 p.m. (4) In subacute toxicity studies urinary LDH was increased on day 2 above the extent after a single dose, but declined on day 3 to reach normal levels after 8 to 10 days (time of sacrifice). The kidneys revealed practically normal histology. The other enzymes studied had also returned to normal values. This indicates some adaptation mechanism.
雄性大鼠单独饲养在代谢笼中，静脉注射头孢噻啶，连续收集24小时尿液样本；然后处死大鼠以获取相应动物的肾脏。测定尿液中蛋白质、氨基肽酶（AP）、碱性磷酸酶（aPP）、乳酸脱氢酶（LDH）和醛缩酶（ALD）的浓度，并在aPP染色切片中计数受损近端小管的百分比。个体动物的结果如下：（1）将动物单独置于代谢笼中后，尿酶浓度发生了较大但无系统性的变化。6-10天后，酶达到稳态水平。（2）单次注射头孢噻啶后，观察到近端小管的剂量依赖性损伤，尿LDH含量与肾小管损伤的相关性最好（r大于0.93），比正常值增加高达1000倍。（3）观察到大鼠肾脏对头孢噻啶的易感性存在昼夜节律，上午7点注射动物时反应最小，下午7点注射后反应最大。（4）在亚急性毒性研究中，尿LDH在第2天高于单次给药后的水平，但在第3天下降，8至10天（处死时间）后恢复正常水平。肾脏组织学基本正常。所研究的其他酶也恢复到正常水平。这表明存在某种适应机制。
