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抗生素肾毒性的基础研究。II. 抗生素对大鼠肾脏溶酶体稳定性影响的研究

[Basic study of nephrotoxicity of antibiotics. II. Studies of the effect of antibiotics on lysosomal stability in rat kidneys].

作者信息

Saito S, Ishikawa H, Koiso K

机构信息

Department of Urology, University of Tsukuba, Japan.

出版信息

Nihon Hinyokika Gakkai Zasshi. 1990 Feb;81(2):282-8. doi: 10.5980/jpnjurol1989.81.282.

Abstract

In order to assess the potential nephrotoxicity of antibiotics, effects of these agents on rat kidney lysosomal membrane were investigated in various conditions. Antibiotics were given to Wistar rats for 5 successive days. After nephrectomy rat lysosomes were separated and their membrane stability was examined by measuring the activities of acid-phosphatase. In addition, after separation of lysosomes from normal untreated Wistar rats, antibiotics were added in the incubation system to assess the in vitro effect of antibiotics. Effects of renal ischemia and the lysosomal membrane stabilizer (cortisol) were also examined. Aminoglycosides antibiotics (streptomycin, kanamycin, gentamycin), doxytetracycline, chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used for this purpose. It was clearly pointed out that aminoglycosides interfered with the lysosomal stability in vivo and in vitro. After a 60 minutes ischemia of the rat kidneys by clamping the renal arteries, effects of antibiotics on administration of 5 successive days on rat lysosomal stability were investigated. It was demonstrated that aminoglycosides also made the lysosomal membrane more unstable. Effects of the lysosomal stabilizer, cortisol, on rat kidney lysosomes were examined. Use of cortisol simultaneously with an antibiotic was more effective than that before and after it.

摘要

为了评估抗生素的潜在肾毒性,在不同条件下研究了这些药物对大鼠肾溶酶体膜的影响。连续5天给Wistar大鼠使用抗生素。肾切除术后分离大鼠溶酶体,并通过测量酸性磷酸酶的活性来检查其膜稳定性。此外,从正常未处理的Wistar大鼠分离溶酶体后,在孵育系统中加入抗生素以评估抗生素的体外作用。还研究了肾缺血和溶酶体膜稳定剂(皮质醇)的作用。为此使用了氨基糖苷类抗生素(链霉素、卡那霉素、庆大霉素)、强力霉素、氯霉素和头孢菌素(头孢噻吩、头孢匹林、头孢替唑、拉氧头孢)。结果清楚地表明,氨基糖苷类抗生素在体内和体外均会干扰溶酶体的稳定性。通过夹闭肾动脉使大鼠肾脏缺血60分钟后,研究了连续5天给药抗生素对大鼠溶酶体稳定性的影响。结果表明,氨基糖苷类抗生素也会使溶酶体膜更不稳定。研究了溶酶体稳定剂皮质醇对大鼠肾溶酶体的作用。皮质醇与抗生素同时使用比在其之前或之后使用更有效。

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