Two-stage carcinogenesis has been widely used as a method for evaluating precancerous lesion on animal experiments. Here we used diethylnitrosamine (DEN), a tumor trigger, and carbon tetrachloride (CCl4), a tumor promoter, to mimic the first two stages of hepatic carcinogenesis. Single intra-peritoneal injection of DEN 1% in combination with repeated intra-peritoneal injection of CCl4 4% for 16 weeks led to the formation of hyperplasia nodules on mouse livers. Microscopic examination also revealed dramatic changes in hepatocellular morphology and architecture: increased cell density and proliferation, abnormalities in cell division and nucleus structure. These changes were not observed in animal treated with NaCI or DEN alone. Repeated injection of CCl4 alone led to alterations on microscopic pictures but did not cause hyperplasia nodules. Our results indicate that DEN in combination of CCl4 causes abnormal proliferation of hepatic cells and evokes hepatic hyperplasia
Hepatocytes ; Cell Proliferation ; Carbon Tetrachloride

The hepatoprotective effects of extracts from Phyllanthus niruri obtained by different extraction procedures were evaluated using mice with acute hepatitis, included by CCL4. The effects of lowering the serum ALT and AST of these extracts were clearly demonstrated. It was founded that the hepatoprotective effect of extract produced a protective action better than a recovery one on. Activities of Extract 3 and ChophytolR were compared
Adenoma ; Hepatocytes ; Phyllanthus ; Carbon Tetrachloride ; Pharmaceutical Preparations

Effects of aqueous extract from the root of Morinda sp. were studied on liver injury induced by a high dose of carbon tetrachloride in rats. The results showed that the extract had a hepatoprotective effect at a dose of 10g/kg of body weight. The effect was similar to that of silymarin at a dose of 25mg/kg of body weight in terms of AST, ALT activities, total serum cholesterol and protein concentrations as well as macro-and microscopic histological studies of the liver.
Liver ; Plants, Medicinal ; Plants ; Carbon Tetrachloride ; rats

The experimental trial was conducted on bull white mice, ddY strain, weight of 18-20g, were randomly assigned to different lots, with 8-15 mice in each lot. Experimental product was total dry lingzhi extract produced by OPC Company which reached standards at basic level. Lingzhi dry powder was prepared with distilled water to make liquid extract with concentration of 15% (15g dry extract/100ml water), 30% and 75%. These liquid extracts were used to test hepatoprotective effect effect of Lingzhi extract on chronic hepatic toxication by DEN and CCl4. The results showed that lingzhi extract did not show microprotective effects. However, lingzhi extract can inhibit hyperplastic nodule formation. On the other hand, lingzhi extract also reduced abnormal cells formation
Drugs, Chinese Herbal ; Liver ; Diethylnitrosamine ; Carbon Tetrachloride

Carbon tetrachloride and dimethylnitrosamine, both potent hepatotoxic agents, affect the hepatic lobules with fatty changes and central necrosis, and hemorrhagic necrosis. To study the effects on morphologic changes of the hepatic lobules in cases of single and repeated treatment of both hepatotoxins, sublethal doses of carbon tetrachloride, 0.4ml/kg, and dimethyl nitrosamine, 40 mg/kg of rats were given introperitoneally single, twice and triple. With interval of 3 days, and the results were as follows: 1. The fatty changes and central necrosis of the hepatic lobules were milder and more quickly disappeared in the rats with twice or triple treatment than single administration of carbon tetrachloride, and regenerative changes of hepatic and sinusoidal cells achieved fater in the rats with repeated administration of carbon tetrachloride than those with single treatment. 2. The hemorrhagic necrosis of the hepatic lobules was not significantly influenced by the times of DMN treatment, but the hyperplastic changes showed more active to animals, with multiple administration of DMN.
Animals ; Carbon Tetrachloride* ; Carbon* ; Dimethylnitrosamine* ; Liver* ; Necrosis ; Rats*

Two rat hepatic intoxication models by high doses CCl4 and PAR were used. The experimental results showed that the oral administration of Panax Notoginseng (aqueous extract) with the dose of 5g/kg body weight has significantly reduced the serum concentrations of SGOT and SGPT with 29.1% and 43.1% respectively in comparison with that of CCl4 - treated control . In PAR - intoxicated group, Panax Notoginseng with the dose of 5g/kg body weight resulted in a marked decrease of SGOT and SGPT serum concentration 97.0% and 75.5%, respectively, which were significantly different from that of group without Panax Notoginseng. The hepatoprotective effect of Panax Notoginseng with the dose of 5g/kg and Silymarin with the dose of 25mg/kg on both CCl4 and PAR hepatic-intoxication models is the same. In histopathological examinations, Panax Notoginseng has improved CCl4 and PAR induced hepatic injuries
Panax notoginseng ; Carbon Tetrachloride ; poisoning ; liver ; rats ; Animal Experimentation

The purpose of this study was to evaluate the influence of phenobarbital (PB) on hepatotoxic effect of carbon tetrachloride (CCI4) which induces centrilobular necrosis in liver. Rats were injected intraperitoneally CCI4 dissolved in olive oil by a dose of 0.4 mg/kg. For change related to PB pretreatment, rats were injected CCI₄ 0.4mg/kg after PB pretreatment. The liver samples were taken in 6, 12, 24, 48, 72 and 120 hours after CCI₄ and/ or PB injection. Extracted liver tissue was examined with light and electron microscopes. The results were summarized as follows: 1. Light microscopic findings: In CCI₄ group, centrilobular necrosis developed from 6 hours after injection, was the most severe in 48 hours, and recovered after 72 hours. In addition to necrosis, fatty change and pale cell change were accompanied. In PB-CCI4 group, necrosis occurred from 6 hours after CCI₄ injection and continued to 72 hours, and the degree of necrosis was more severe than that of CCI₄ group and pale cell change was decreased. 2. Electron microscopic findings: In CCI4 group, the early principal change was clumping and vesicular dilatation of endoplasmic reticulum. In PB-CCI₄ group, the degenerative change of endoplasmic reticulum was aggravated and the mitochondria also revealed severe degenerative change. According to the results, it was revealed that CCI₄ hepatotoxicity primarily began with the damage of endoplasmic reticulum, then damage of other cell organelles and cell necrosis followed, and these cytotoxic effects were aggravated by PB pretreatment.
Animals ; Carbon Tetrachloride* ; Carbon* ; Dilatation ; Endoplasmic Reticulum ; Liver ; Mitochondria ; Necrosis ; Olive Oil ; Organelles ; Phenobarbital* ; Rats*

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.
Animals ; Carbon Tetrachloride* ; Carbon* ; Dilatation ; Dimethylnitrosamine ; Hepatocytes* ; Liver ; Necrosis ; Olive Oil ; Rats

The kiwi (Actinidia deliciosa) is well known to contain anti-oxidants. In this study, we investigated the anti-oxidant effects of kiwi extract on carbon tetrachloride (CCl4) induced liver injury in BALB/c mice. The radical scavenging effect of 80% methanol extract of Halla-Gold kiwi was observed. For the animal study, mice were randomly divided into four groups: normal group, CCl4-induced model group, kiwi extract administered group, and silymarin treated group. The kiwi extract was provided daily for 10 days. At the 24 h after last administration, CCl4 was injected. The kiwi extract showed strong inhibitory effect of DPPH radicals and superoxide scavenging. In animal study, administration of CCl4 resulted in significantly elevated plasma levels of ALT and AST but they decreased in kiwi-extract pretreated group. Anti-oxidant enzymes such as GSH-px and GSH-rd were restored in the kiwi extract treatment group. Histopathological degeneration was also prevented in the kiwi extract treated group compared with of the control group, which exhibited CCl4-induced hepatotoxicity. On the basis of the obtained results, it can be concluded that kiwi extract showed protective effects, not only as anti-oxidant effects, but also in the protection of hepatotoxicity in CCl4-intoxicated mice.
Animals ; Antioxidants ; Carbon ; Carbon Tetrachloride ; Cytochrome P-450 CYP2E1 ; Fruit ; Liver ; Methanol ; Mice ; Plasma ; Silymarin ; Superoxides

This study was designed to investigate the synergetic hepatoprotective effects from a mixture of Korean Red Ginseng and Pueraria Radix on carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice. Liver toxicity was induced by intraperitoneal administration of CCl₄ (0.6 mg/kg) in 12 groups of ICR mice. The negative control group was given CCl₄ without test samples and the normal group was given no treatment. Among treatment groups, the RGAP treatment (Korean Red ginseng acetic acid extract : Pueraria Radix water extract, w/w, 38.4:57.6) decreased CCl₄-elevated ALT (101.60 IU/L), AST (833.89 IU/L), and LDH (365.02 IU/L) levels in the serum, and increased the SOD (11.03 unit/mg protein) and CAT (0.37 unit/mg protein) levels and the LPO levels (59.09 µM/g tissue) more than that in the mice group with CCl₄-induced control group hepatotoxicity. These results suggest that administration of a mixture of Korean Red ginseng and Pueraria Radix decreases CCl₄-induced liver damage and enhances antioxidant activity in mice and imply that administration of the mixture in a certain ratio is more effective than single administration of either Korean Red ginseng or Pueraria Radix alone.
Acetic Acid ; Animals ; Carbon Tetrachloride* ; Carbon* ; Cats ; Liver* ; Mice* ; Mice, Inbred ICR ; Panax* ; Pueraria* ; Water