Tomic Zdenko, Milijasevic Boris, Sabo Ana, Dusan Lalosevic, Jakovljevic Vida, Mikov Momir, Majda Satman, Vasovic Velibor
Institute of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia.
Eur J Drug Metab Pharmacokinet. 2008 Oct-Dec;33(4):253-60. doi: 10.1007/BF03190881.
In the last years there appeared many articles about the adverse influence of non-steroidal anti-inflammatory drugs on the liver and heart. This study is concerned with the influence of the duration of treatment with diclofenac and ketoprofen on the macroscopic and microscopic changes in the liver, lungs, heart, and kidneys in rats. Experiments were carried out on mature Wistar strain rats. Animals of test groups received diclofenac and ketoprofen in a dose of 8 mg/kg/day (equivalent to the therapeutic dose for man) during 7 per os (p.o.) or 28 days intraperitoneally (i.p.), whereas controls received physiological solution p.o. A high morbidity was observed in the animals receiving diclofenac p.o. and somewhat lower in those treated with ketoprofen. On the other hand, the rats got through the 28-day i.p. treatment with both drugs mainly without significant complications. Macroscopic examinations revealed some changes in treated rats: distension of the stomach, ascites, fibrin deposits on the internal organs, lung effusion and the changes in color and structure of the liver. These changes were more frequent in the group of rats receiving diclofenac for the 7 days compared with those that received ketoprofen for the same time. It may be thought that the high mortality and macroscopic changes in the internal organs of experimental animals are a consequence of the microscopic changes in the liver and its lowered function.
在过去几年里，出现了许多关于非甾体抗炎药对肝脏和心脏不良影响的文章。本研究关注双氯芬酸和酮洛芬的治疗时长对大鼠肝脏、肺、心脏和肾脏宏观及微观变化的影响。实验在成年Wistar品系大鼠身上进行。试验组动物经口（p.o.）7天或腹腔注射（i.p.）28天给予剂量为8毫克/千克/天的双氯芬酸和酮洛芬（相当于人类治疗剂量），而对照组经口给予生理盐水。经口给予双氯芬酸的动物中观察到高发病率，用酮洛芬治疗的动物发病率略低。另一方面，用这两种药物进行28天腹腔注射治疗的大鼠主要没有明显并发症。宏观检查发现治疗后的大鼠有一些变化：胃扩张、腹水、内脏上有纤维蛋白沉积、肺积液以及肝脏颜色和结构的变化。与同期接受酮洛芬治疗的大鼠相比，接受双氯芬酸7天治疗的大鼠组中这些变化更频繁。可以认为实验动物内脏的高死亡率和宏观变化是肝脏微观变化及其功能降低的结果。
