Katoh M, Sugimoto T
Nihon Yakurigaku Zasshi. 1982 Jul;80(1):83-91.
Effect of malotilate on chronic liver injury induced by carbon tetrachloride (CCl4) was studied in rats. Rats were intraperitoneally injected with CCl4 dissolved in olive oil at a rate of 0.5 ml/kg, twice a week for 10 weeks. Malotilate mixed with a laboratory chow diet at a concentration of 0.2% was fed to the rats for 10 weeks, the increases of liver triglycerides (TG), malonedialdehyde (MA), and 4-hydroxyproline contents, and decrease of liver protein content were observed at 5, 8, and 10 weeks after initiation of CCl4-injection. In the histopathological study, vacuolation at 5 weeks, vacuolation and fibrosis at 8 weeks, and extreme fibrosis at 10 weeks were observed in rat liver with CCl4-injection. In the rats fed the diet containing malotilate for 10 weeks, these changes of biochemical parameters and histopathological findings were not observed at any time and only slight increase of liver TG and slight vacuolation at 10 weeks was observed. When rats were fed the diet containing malotilate for the last 5 or 2 weeks, these changes of biochemical parameters and histopathological findings caused by CCl4 were improved thereafter. Although the covalent bindings of the radioactivity from 14CCl4 to liver microsomal phospholipids were slightly depressed by malotilate feeding, it is difficult to explain the protective effect of malotilate on the liver injury only by this phenomenon. Other probable mechanisms for this effect were discussed.
研究了马洛替酯对四氯化碳(CCl4)诱导的大鼠慢性肝损伤的影响。大鼠腹腔注射溶解于橄榄油中的CCl4,剂量为0.5 ml/kg,每周两次,共10周。将浓度为0.2%的马洛替酯与实验室常规饲料混合后喂给大鼠10周,在开始注射CCl4后的第5、8和10周观察到肝脏甘油三酯(TG)、丙二醛(MA)和4-羟脯氨酸含量增加,以及肝脏蛋白质含量降低。在组织病理学研究中,注射CCl4的大鼠肝脏在第5周出现空泡化,第8周出现空泡化和纤维化,第10周出现严重纤维化。在喂食含马洛替酯饲料10周的大鼠中,在任何时候均未观察到这些生化参数变化和组织病理学改变,仅在第10周观察到肝脏TG略有增加和轻微空泡化。当大鼠在最后5周或2周喂食含马洛替酯的饲料时,由CCl4引起的这些生化参数变化和组织病理学改变随后得到改善。尽管喂食马洛替酯会使14CCl4的放射性与肝微粒体磷脂的共价结合略有降低,但仅通过这一现象难以解释马洛替酯对肝损伤的保护作用。讨论了这种作用的其他可能机制。