The study was designed to investigate the role of hepatic metabolic activity on body burden of HCH residue. Male albino rats were orally administered 0, 5, and 10 mg/kg HCH for 90 days, followed by either sodium phenobarbital or carbon tetrachloride treatment for 0, 15 and 30 days after withdrawal of their respective HCH administration. The liver weight was significantly increased at 30 days after the administration of phenobarbital and carbon tetrachloride in both 5 mg and 10 mg/kg HCH withdrawal groups when compared to control. HCH residue was maximum in fat followed by adrenal > thymus > liver > kidney > spleen > tests > brain > plasma. Carbon tetrachloride caused an accumulation of HCH residues in the liver 15 and 30 days after administration of both doses of HCH. Phenobarbital did not show significant variation in HCH residues in hepatic tissue. Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities. Significant decreases in activities were observed by carbon tetrachloride when compared to animals treated with HCH alone. The overall results clearly suggest the role of P450 protein on the body burden of HCH residues.
Animals ; Carbon Tetrachloride ; toxicity ; Inactivation, Metabolic ; Lindane ; pharmacokinetics ; toxicity ; Liver ; enzymology ; metabolism ; pathology ; Liver Function Tests ; Male ; Organ Size ; drug effects ; Phenobarbital ; toxicity ; Rats ; Tissue Distribution

BACKGROUNDLiver fibrosis normally progresses to cirrhosis and destroys the normal architecture of the liver, resulting in liver dysfunction and irreversible cirrhosis. The aim of this study was to investigate the anti-fibrosis effect and the possible underlying mechanisms of decorin.

METHODSThe mice model of liver fibrosis was induced by intraperitoneal injection of 50% (v/v) of carbon tetrachloride (CCl4) diluted in olive oil (1 ml/kg body weight) once every 2 days for 5 weeks. Three weeks after injecting CCl4 intraperitoneally, mice were randomly divided into normal control with vehicles only (olive oil), mouse model given CCl4 only, and CCl4 plus decorin (DCN, 250 µg/kg). Two weeks later, all the mice were sacrificed and their liver tissues were analyzed for the expressions of genes related to liver fibrosis and under hematoxylin-eosin staining, Masson staining, and immunohistochemical staining of all groups. Aspartate transaminase, alanine transaminase, and total bilirubin of the serum were determined for evaluation of the liver function.

RESULTSExogenous protein decorin could reduce liver fibrosis induced by CCl4 in mice. The degree of fibrosis in the experimental group was alleviated, and the contents of collagen fibers were lower in the experimental group than those of the control group. In addition, expressions of transforming growth factor β1 and α-smooth muscle actin decreased in the experimental group.

CONCLUSIONSTaking liver fibrosis model of mouse as the experimental target and by injecting exogenous protein decorin into the model, we confirmed that decorin could inhibit the expression of proteins related to fibrosis and reduce the formation of liver fibrosis in mice.

Animals ; Carbon Tetrachloride ; toxicity ; Decorin ; therapeutic use ; Immunohistochemistry ; Liver Cirrhosis ; chemically induced ; prevention & control ; Mice ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the alteration of apparent diffusion coefficient (ADC) in diffusion-weighted MR imaging (MR-DWI) of liver fibrosis and its pathological basis in rabbits.

METHODSFive rabbits in the control group and 22 with experimental liver fibrosis induced by transperitoneal injection of carbon tetrachloride (CCl4) were examined with MR-DWI. Diffusion-weighted SE EPI sequence with a relatively high b factor (b=600 s/mm2) was used to measure the ADC. The mean values of ADC were compared among the rabbits in different stages of liver fibrosis and analyzed in relation to the pathological findings.

RESULTSThe mean ADC value decreased significantly with increased severity of liver fibrosis (P<0.05). Pathologically, the amount and extension of fibrotic matrix increased, and the hepatic necroinflammation worsened with the progression of the liver fibrosis.

CONCLUSIONThe ADC value decreases with the progression of liver fibrosis possibly as the result of water diffusion limitation due to increased fibrous tissue in the liver and abnormal water diffusion within the intracellular and extracellular spaces.

Animals ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis ; chemically induced ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Male ; Rabbits ; Random Allocation

OBJECTIVETo assess whether Angiotensin II (Ang II) and carbon tetrachloride (CCl(4)) used in combination could accelerate the process of fibrosis and whether Ang II play a role in exagerating hepatic fibrosis in rats.

METHODSAng II was injected into the abdominal cavity of Sprague-Dawley (SD) rats together with subcutaneous injection of CCl(4). Rats were killed after 14 and 28 d. Blood serum and liver specimen were collected. The extent of fibrosis in the stained liver tissue sections was determined with the KS 400 Image Analysis System.

RESULTSRats receiving Ang II and CCl(4) for 28 d showed extensive liver fibrosis. Along with the increase of hepatic fibrosis, the serum concentration of Ang II went up gradually.

CONCLUSIONSA combination of Ang II and CCl(4) would accelerate the process of hepatic fibrosis. Ang II probably took part in the occurrence of heparic fibrosis.

Alanine Transaminase ; blood ; Angiotensin II ; blood ; toxicity ; Animals ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis, Experimental ; chemically induced ; Male ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System ; physiology

BACKGROUND/AIMS: It is well known that alcohol enhances the toxicity of CCl4. We tried to establish an alcoholic liver cirrhosis model by administration of alcohol and CCl4 to rats. We also wanted to know the hepatoprotective effect of low doses of lipopolysaccharide(LPS) in this animal model. METHODS: Of 20 female adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were ingested with 10% alcohol and 50% 1mL/kg CCl4 intragastrically by Sonde twice a week(group 2) The remaining 6 were ingested with 10% alcohol, CCl4, and 0.1mg/kg LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated semiquantitatively on a scale of 0(none) to 3(cirrhosis). RESULTS: 1) After 10 weks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2 and 3 but there was no fibrotic change in group 1. 2) There was no significant difference in pathological grading between groups 2 and 3. CONCLUSIONS: Hepatic fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCl4 ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose LPS by semiquantitative evaluation of pathological grading.
Animals ; Carbon Tetrachloride Poisoning/*complications ; English Abstract ; Ethanol/*toxicity ; Female ; Lipopolysaccharides/*administration & dosage ; Liver/pathology ; Liver Cirrhosis, Alcoholic/pathology/*prevention & control ; Rats ; Rats, Sprague-Dawley

Intralobular fibrogenesis of the liver following hepatocellular damage has long been a controversial subject in regard to its initiation and prevention. To investigate the site of hepatic fibrogenesis and the effect of glucocorticoids during the early stage of hepatic fibrogenesis, dexamethasone was administered in a daily dose of 8 mg/rat following a sing1e dose of CCl4 to induce hepatic necrosis with or without combination of vitamin A to Stimulate lipocytes. Light and electron microscopic examinations of the liver at 2, 4, 6, 8 and 10 days after CCl4, vitamin A and dexamethasone treatment demonstrated that hepatocellular damage stimulated perisinusoidal lipocytes which in turn actively produced collagens. Concomitant administration of vitamin A enhanced stimulation of lipocytic activity and consequently increased collagen formation, while administration of dexamethasone suppressed lipocytic activity leading to an inhibition of collagen formation.
Animal ; Carbon Tetrachloride/toxicity ; Dexamethasone/pharmacology* ; Histocytochemistry ; Liver/drug effects ; Liver/pathology* ; Liver/ultrastructure ; Male ; Microscopy, Electron ; Necrosis ; Rats ; Vitamin A/pharmacology

Fraxinellone, the major component of Cortex Dictamni, is naturally degraded limonids compound. Fraxinellone has significant anti-inflammatory activity in acute liver injury model. However, the low solubility and permeability of fraxinellone limited its potential application and even therapeutic effects. The aim of the paper is to increase oral bioavailability of fraxinellone, thus improving its hepatoprotection effect in vivo. We evaluated the effects of different pH values and different solubilizer (PEG 6000, PVP K30, HP-beta-CD, F68 and SDS) on the solubility of fraxinellone. The results showed that HP-beta-CD increased solubility of fraxinellone up to 155 times compared to that of water. More than 2. 1 mg mL1 fraxinellone can be resolved when adding 20% HP-beta-CD. Mouse acute liver injury model induced hy CCl4 was used to evaluate in vivo activity of fraxinellone with or without HP-beta-CD. The result shows that the hepatoprotective activity of fraxinellone in 20% HP-beta-CD solution has been significantly improved compared with that of fraxinellone solution without HP-beta-CD: the former inhibited 59 percent the increase of enzyme activity of ALT in liver, while the latter only inhibited 20 percent. A LC-MS/MS method was also developed to determine the oral bioavailability of fraxinellone. Fraxinellone solution with or without HP-betaCD were administered intra-gastrically to rats, and it was found that the bioavailahility of fraxinellone with HP-beta-CD was 23%, while only 5% without HP-beta-CD. The result showed that HP-beta-CD can significantly increase the solubility and permeability of fraxinellone, and improve bioavailability 3. 5 fold in vivo acute liver injury model as well as administration.
Animals ; Benzofurans ; chemistry ; pharmacokinetics ; pharmacology ; Biological Availability ; Carbon Tetrachloride ; toxicity ; Female ; Hydrogen-Ion Concentration ; Liver ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Rats ; Rats, Sprague-Dawley ; Solubility

OBJECTIVETo study the protective effect of Blueberry against rat hepatic fibrosis and the effect of Blueberry on HO-1 expression patterns.

METHODSA total of 45 SD rats were randomly divided into five groups namely control group (group A), model group (group B), blueberry group (group C), Dan-shao-hua-xian (DSHX) capsule group (group D) and blueberry +Dan-shao-hua-xian group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4 and high-lipid/low-protein diet for 8 weeks except the control group which accepted saline alone. The level of alanine aminotransferase (ALT) in serum was examined. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. by the xanthine oxidase method and the thiobarbituric acid method. The pathology of hepatic fibrosis was evaluated by hematoxylin and eosin (H and E) staining. The Expression of HO-1 was detected by real-time RT-PCR, immunohistochemical techniques and western blotting.

RESULTSSerum ALT levels in every prevention group was lower than the group B [(149.44+/-16.51), (136.88+/-10.07), (127.38+/-11.03) vs (203.25+/-31.62) U/L, F = 92.498, P < 0.05], the SOD of liver homogenate in prevention group was significantly higher and the MDA was lower compared with the group B [SOD: (1.36+/-0.09), (1.42+/-0.13), (1.50+/-0.15) vs (1.08+/-0.19) U/mg, F = 13.671, P < 0.05; MDA: (0.294+/-0.026), (0.285+/-0.025), (0.284+/-0.028) vs (0.335+/-0.056) nmol/mg, F = 20.809, P < 0.05]. The pathological stages of hepatic fibrosis were all significantly reduced in prevention group (Chi2 test = 24.956, P < 0.05). Compared with group A, the mRNA and protein expressions of HO-1 were elevated (F = 4.549, 22.926, P < 0.05) in group B and increased in group C-E, but there is no significant difference existed.

CONCLUSIONBlueberry may have preventive and protective effects on CCl4-induced hepatic fibrosis by reducing lipid peroxidation. However, these effects may not be related to the activation of HO-1 during long-term of CCl4.

Animals ; Blueberry Plants ; chemistry ; Carbon Tetrachloride ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase (Decyclizing) ; blood ; Liver Cirrhosis, Experimental ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of Cordyceps sinensis (CS) on pancreatic islet B cells of experimental hepatic fibrogenesis rats.

METHODSRats were randomly allocated into three groups: normal group, model group and CS group. The rats in the latter two groups were administered with CCl(4) solution to induce liver fibrosis, the CS group was also treated with CS 10 days after the beginning of CCl(4) administration. Rats in normal group were sacrificed at the beginning of the experiment, while the rats in the other two groups were sacrificed randomly at the end of the third and sixth weeks. The rats' islets were isolated and cultured in vitro, then the basal insulin level of the islets and the serum level of insulin were determined by radioimmunological assay.

RESULTSIt seemed no change that the levels of serum insulin and basal insulin between the model group and the normal group at the third week. But at the sixth week, both insulin levels in the model group were higher than those in the normal group (52.6 mU/L2.5 mU/L vs 23.7 mU/L 2.3 mU/L, q=13.01, p<0.05; 52.94muU/ml 13.12muU/ml vs 35.16muU/ml 5.64muU/ml, q=10.06, p<0.01). No significant change could be seen in the serum levels of insulin between the CS group and the model group at the third and sixth weeks. But the basal insulin levels in the CS group were apparently higher than those in the model group at the third and sixth weeks (156.63muU/ml 6.57muU/ml vs 39.64muU/ml 3.95muU/ml, q=66.94, p<0.001; 140.44muU/ml 38.53muU/ml vs 52.94muU/ml 13.12muU/ml, q=12.98, p<0.01).

CONCLUSIONCordyceps sinensis can increase the basal insulin level of the islets in CCl(4)-induced liver fibrosis rats.

Animals ; Carbon Tetrachloride ; toxicity ; Cordyceps ; Female ; Insulin ; blood ; secretion ; Islets of Langerhans ; physiopathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; pathology ; physiopathology ; therapy ; Male ; Rats ; Rats, Wistar

BACKGROUND: The current study aimed to investigate the hepatoprotective effects of Sasa veitchii extract (SE) on carbon tetrachloride (CCl)-induced liver fibrosis in mice. METHODS: Male C57BL/6J mice were intraperitoneally injected with CCl dissolved in olive oil (1 g/kg) twice per week for 8 weeks. SE (0.1 mL) was administered orally once per day throughout the study, and body weight was measured weekly. Seventy-two hours after the final CCl injection, mice were euthanized and plasma samples were collected. The liver and kidneys were collected and weighed. RESULTS: CCl administration increased liver weight, decreased body weight, elevated plasma alanine aminotransferase, and aspartate aminotransferase and increased liver oxidative stress (malondialdehyde and glutathione). These increases were attenuated by SE treatment. Overexpression of tumor necrosis factor-α was also reversed following SE treatment. Furthermore, CCl-induced increases in α-smooth muscle actin, a marker for hepatic fibrosis, were attenuated in mice treated with SE. Moreover, SE inhibited CCl-induced nuclear translocation of hepatic nuclear factor kappa B (NF-κB) p65 and phosphorylation of mitogen-activated protein kinase (MAPK). CONCLUSION These results suggested that SE prevented CCl-induced hepatic fibrosis by inhibiting the MAPK and NF-κB signaling pathways.
Animals ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis ; chemically induced ; drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Random Allocation ; Sasa ; chemistry