OBJECTIVE: To investigate the effect of prostaglandin E1 (PGE1) on the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in experimental liver fibrosis rats. METHODS: The liver fibrosis model was established by carbon tetrachloride. Rats were divided into a control group and PGE1-treated group. The pathological changes of the liver tissue from the two groups, the semi-quantitative analysis of hepatitic activity in HE stain sections, the pathological image quantitative analysis of the fibrosis degree, TIMP-1 positive cells, and the content of collagen were synthetically analysed. RESULTS: The mark changes of liver pathology in HE stain sections were that the degree of hepatitic activity in the PGE1-treated group was obviously lower than that in the control group (P < 0.05). The fibrosis degree, TIMP-1 positive cells and the collagenous fibers decreased in the PGE1-treated group (P <0.05). CONCLUSION PGE1 has an anti-hepatofibrosis effect in the experimental rats, the inflammation of liver is light, and the proliferation of collagenous fibers can be restrained, whose mechanism is probably associated with the suppression of TIMP-1 expression caused by PGE1.
Alprostadil ; pharmacology ; Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

Animals ; Bone Marrow Cells ; cytology ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Cell Differentiation ; Cells, Cultured ; Genetic Therapy ; methods ; Hepatocyte Growth Factor ; genetics ; pharmacology ; Hepatocytes ; cytology ; Liver Cirrhosis, Experimental ; therapy ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Rats ; Rats, Wistar

Animals ; Antioxidants ; pharmacology ; Carbon Tetrachloride Poisoning ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Enzyme Inhibitors ; pharmacology ; Male ; Mice ; Protective Agents ; pharmacology ; Ribonucleases ; antagonists & inhibitors

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

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

The authors have demonstrated the effect of sodium selenite on the hepatotoxicity due to carbon tetrachloride, by observing the distribution and disaggregation of the pyroninophilic granules in the hepatic cell of the mature male albino mice. Each experimental mouse of the selenite and the selenite plus carbon tetrachloride groups was given a single dose of 4 ug. of sodium selenite per kilogram of body weight and that of the control and the carbon tetrachloride groups was given 0.1 ml. of distilled water alone. Six hours after the first administration of distilled water or sodium selenite, the experimental mice of the carbon tetrachloride and the selenite plus carbon tetrachloride groups were given a single dose of l.0 ml. of carbon tetrachloride per kilogram of body weight and those of the selenite groups were given 0.l ml. of paraffin oil alone. Following the 1ast administration of carbon tetrachloride or paraffin oil, the mice were sacrificed by bleeding (cutting the common carotid artery) at the intervals of 2,3,4,6,8, and 12 hours respectively. Histochemical preparations were stained by the methyl-green and pyronin method and oil red 0 method. The hepatotoxicity due to the administration of carbon tetrachoride was evident in the hepatic cells; the pyroninophilic granlues were partly reduced in volume in the hepatic cells of the centrilobular and the intermediate zones as early as the 3 hour-period, and markedly reduced or disappeared in the centrilobular and some part of the intermediate zones associated with hydropic degeneration as well as in the 6 hour-period. Thereafter marked reduction or dissolution of the pyroninophilic granules was found and extended as the periportal zone at the 12 hour-period. However, the pyroninophilic granules in the hepatic cells of selenite plus carbon tetrachbride group showed no significant changes in the hepatic cells of these zones, compared to the histochemical feature of the granules in the hepatic cells of the control and the selenite groups. Consequently it is suggested that the lipid peroxidative decomposition of the microsomal membranes, which is induced with carbon tetrachloride, would be prevented by a previous administration of sodium selenite.
Animal ; Carbon Tetrachloride Poisoning*/pathology ; Cell Nucleus/drug effects ; Cytoplasm/drug effects ; Cytoplasmic Granules ; Lipids ; Liver/drug effects* ; Liver/pathology ; Male ; Mice ; Selenium/pharmacology* ; Vacuoles/drug effects

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

OBJECTIVES: To observe the preventive and therapeutic action of Yuyin Ruangan Granule (YRG, Traditional Chinese Medicine) in hepatic fibrosis rats model and its effect on transforming growth factor-β1 (TGF-β1) expression. METHODS: The Wistar rats were randomly divided into 6 group (=10), and the model of hepatic fibrosis rats was established by subcutaneous injected with carbon tetrachloride (CCL4), fed on high-fat diet and 20% ethanol for 6 weeks, to survey the effect and mechanism of YRG preventing hypatic fibrosis by detecting liver function (the activity of alanine aminotransferase(ALT), aspartate aminotransferase(AST), etc.) of liver fibrosis rats, liver fibrosis indicators (hyaluronic acid, Ⅲ procollagen, type IV collagen, laminin and hepatic pathology, etc.), and TGF-β1 expression in liver tissue after 6 weeks treated with YRG through intragastric administration (q. d.). RESULTS: At the 7 week, fibrotic lesions appears distinctly in liver tissue of model group compared with control group (<0.01), YRG of 6.2~28.8 g/kg could significantly decrease hepatic index, ALT and AST activities, content of hyaluronic acid(HA), Ⅲ procollagen (PCⅢ), type Ⅳ collagen(C-Ⅳ), laminin (LN) in serum, relieve liver fibrosis pathological changes and inhibit TGF-β1 expression in fibrotic liver tissue (<0.05, <0.01). CONCLUSIONS YRG has significantly preventive effects on liver fibrosis rats model, and it may be one of its mechanisms to inhibit expression of TGF-β1.
Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; pharmacology ; Liver ; drug effects ; metabolism ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism

At present, there were few studies about the effects of cultivation measures on the quality and pharmacological activity of medicinal plants. To explore the hepetoprotective activity of Sedum sarmentosum aqueous extracts after different water treatments, S. sarmentosum were planted under five water treatments for 60 days, namely 15%-20% FC (field capacity, S1), 35%-40% FC (S2), 55%-60% FC (S3), 75%-80% FC(S4), and 95%-100% FC (S5) and CCl₄ drug-induced liver injury model in vitro was used. Cell viability, cell cycle, and cell apoptosis were individually detected by MTT, PI single staining, and Annexin-V FITC/PI double staining assays. Additionally, ALT, AST and antioxidant index in supernatant were determined by colorimetry. The results showed that, compared with the model group, S. sarmentosum aqueous extract could significantly improve the HepG2 cell viability. Among the five S. sarmentosum groups, the cell viability of S4 (75%-80% FC) treatment was the highest, and the cell apoptosis was the least. Meanwhile, the level of ALT, AST, and MDA in S4 was the lowest, but it achieved the highest level of SOD and GSH. Taken together, different water treatments had great influence on hepatoprotective effect of S. sarmentosum, and the soil moisture of the 75%-80% FC is beneficial to the hepetoprotective activity of S. sarmentosum.
Antioxidants ; metabolism ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; Hep G2 Cells ; Humans ; Plant Extracts ; pharmacology ; Sedum ; chemistry ; Soil ; Water

Bicyclol is a new generation of anti-hepatitis drug with China's own intellectual property rights. The chemical structure of bicyclol is new and original. Pharmacological research showed that it has high clinical efficacy in treating chronic hepatitis (HBV) patients and lower side effects. Two metabolites of bicyclol have been isolated: M2 (4-hydroxy-4'-methoxy-5, 6, 5', 6'-bis (methylenedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl) and M3 (4'-hydroxy-4-methoxy-5, 6, 5', 6'-bis (methyl enedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl). To further study the mechanism, safety, and effectiveness of bicyclol, the M2 and M3 have been total synthesized. The synthesis route is as following: the carboxyl and phenolic hydroxyl group of the aromatic bromide had been separately protected by bromobenzyl, coupling through the intermolecular asymmetric Ullmann reaction and then catalyst hydrogenated, borane reducted, two metabolites of bicyclol M2 and M3 were obtained. The structures were determined by IR, 1H NMR, HRMS. Comparison of hepatoprotective activity of bicyclol and the two metabolites on experimental liver injury, the potency of the metabolites were lower than that of bicyclol.
Alanine Transaminase ; blood ; Animals ; Benzodioxoles ; chemical synthesis ; chemistry ; pharmacology ; Biphenyl Compounds ; metabolism ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; Mice