ABSTRACT
The purpose of this study was to evaluate the influence of high dose carbon tetrachloride (CCI4) on the hepatotoxic effect of dimethylnitrosamine (DMN) which induces acute hemorrhagic necrosis in liver. Rats were injected intraperitoneally DMN dissolved in physiologic saline by a dose of 40 mg/kg. For changes related to CCI⁴ pretreatment, rats were injected intraperitoneally CCI⁴ dissolved in olive oil by a dose of 0.4 mg/kg, and then injected DMN. The livers were extracted from the rats 3, 6, 12, 24, 48, 72, and 120 hours after CCI⁴ and/ or DMN injection. Liver tissues were examined with light and electron microscopes. The results were summarized as follows; Light microscopic findings: Severe centrilobular hemorrhagic necrosis developed from 12 hours after injection of DMN and continued to 120 hours. On injection of DMN after CCI4 pretreatment, Massive necrosis occurred early. But active regenerative changes were produced in 24 hours. In 120 hours, the liver recovered in almost normal appearance. The degree of necrosis in pretreated group was similar to that in DMN injection only, and the time of recovery was faster in pretreated group. Electron microscopic findings: The early change was mainly disorganization of RER in DMN injection, and clumping and vesicular dilatation of ER in injection of CCI4. In pretreatment group, the early change was similar in appearance with CCI4 group, but severer in degree. According to the results, it was revealed that acute toxic effect of DMN was recovered more rapidly in pretreatment group. Thus it was suggested that CCI4 had protective effect in DMN hepatotoxicity.