1.Effect of prostaglandin E1 on the expression of tissue inhibitor of metalloproteinase-1 in experimental liver fibrosis rats.
Shao-jun LIU ; Shou-rong SHEN ; Xiao-yan WANG ; Wu-liang TANG ; Fen WANG
Journal of Central South University(Medical Sciences) 2006;31(3):383-386
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
2.Treatment of CCl4 induced chronic liver injury with bone marrow mesenchymal stem cells overexpressing hepatocyte growth factor.
Li-sha WANG ; Hai-feng DUAN ; Jiang-wei HU ; Qun-wei ZHANG ; Hua WANG ; Zhuo-zhuang LU ; Zu-ze WU ; Li-sheng WANG
Chinese Journal of Hepatology 2005;13(12):934-936
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
4.Histochemical and Ultrastructural Studies of Hepatic Fibrogenesis; Its Initiation and the Effect of Dexamethasone in Rats.
Chang Jin KIM ; Chan Il PARK ; Chung Sook KIM ; Yoo Bock LEE
Yonsei Medical Journal 1982;23(2):89-100
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
5.Sasa veitchii extract protects against carbon tetrachloride-induced hepatic fibrosis in mice.
Hiroki YOSHIOKA ; Tsunemasa NONOGAKI ; Shiori FUKAYA ; Yoshimi ICHIMARU ; Akito NAGATSU ; Masae YOSHIKAWA ; Hirohisa FUJII ; Makoto NAKAO
Environmental Health and Preventive Medicine 2018;23(1):49-49
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
6.Effect of sodium selenite on the hepatotoxicity induced with carbon tetrachloride.
Kyu Sik LEE ; Tai Sun SHIN ; Kum Duck CHOI
Yonsei Medical Journal 1973;14(1):53-62
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
7.Effects of blueberry on the expression patterns of heme oxygenase-1 in rats with hepatic fibrosis.
Yu-ping WANG ; Ming-liang CHENG ; Bao-fang ZHANG ; Jun WU
Chinese Journal of Hepatology 2010;18(9):656-660
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
8.Synthesis of metabolites of bicyclol.
Ye TANG ; Wei HU ; Yan LI ; Chun-zhen ZHANG
Acta Pharmaceutica Sinica 2007;42(10):1054-1057
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
9.Improving the solubility of fraxinellone to increase its oral bioavailability and hepatoprotective action against acute liver injury in mice.
Qi-Qiong RAN ; Li-Ping RUAN ; Dan-Ni ZHU ; Bo-Yang YU
Acta Pharmaceutica Sinica 2007;42(6):675-680
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
10.Effects of total C-21 steroidal glucosides from Cynanchum auriculatum on oxidative stress pathway in mice with liver injury.
Wei-Wei CUI ; Yun-Ru PENG ; Yong-Fang DING
China Journal of Chinese Materia Medica 2019;44(14):2960-2965
The study aimed to investigate the mechanism of hepatoprotective effect of C-21 steroidal glucosides from Cynanchum auriculatum( Baishouwu) on oxidative stress in mice with liver injury. Mice were randomly divided into normal group,model group,positive control group,Baishouwu high group and Baishouwu low group. The liver injury model was induced by intraperitoneal injection of CCl4 peanut oil solution. All mice were sacrificed to collect blood and liver specimens. The activities of serum levels of ALT and AST were detected. The content of MDA and the activity of SOD in liver homogenate were examined by colorimetry method. Tissues were stained with hematoxylin-eosin for histological examination. The hepatic protein expressions of NF-κB p65,p-IκBα,i NOS and COX-2 were detected by Western blot. The mRNA expressions of TNF-α and IL-6 were determined by RT-PCR. It was found that treatment with C-21 steroidal glucosides from Baishouwu successfully attenuated liver injury induced by CCl4,as shown by decreased levels of serum biochemical indicators( AST,ALT)( P<0. 01). Administration of total C-21 steroidal glucosides enhanced the activity of SOD( P<0. 01) and decreased the content of MDA( P<0. 01) in liver homogenate. Microscopic features suggested that treatment with C-21 steroidal glucosides from Baishouwu was effective in inhibiting CCl4-induced hepatocyte edema and degeneration. Further studies showed that NF-κB p65 overexpression induced by CCl4 was decreased by C-21 steroidal glucosides,leading to the markedly down-regulated protein expression levels of p-IκBα,i NOS and COX-2,as well as the depression of TNF-α and IL-6 mRNA expressions. In conclusion,total C-21 steroidal glucosides from Baishouwu exhibited potent effect on oxidative stress pathway in mice with liver injury induced by CCl4,with enhanced activity of SOD,decreased content of MDA,and down-regulated levels of NF-κB p65,p-IκBα,i NOS and COX-2.
Animals
;
Carbon Tetrachloride
;
Chemical and Drug Induced Liver Injury
;
drug therapy
;
Cynanchum
;
chemistry
;
Glucosides
;
pharmacology
;
Hepatocytes
;
drug effects
;
Liver
;
drug effects
;
Mice
;
Oxidative Stress
;
Random Allocation