AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver ...AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.展开更多
AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha...AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.展开更多
[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and ...[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and CCl_4 was used to induce hepatocellular injury. Interventions were carried out with Saikosaponin d and Baicalin at different dosage. The proliferation of L-02 cells in each group was determined by methylthiazolyl tetrazolium( MTT) assay; the levels of AST and ALT in the culture supernatants were detected by enzyme-linked immunosorbent assay( ELISA); the expressions of TLR4 and NFκBp65 proteins in each group were determined by immunohistochemistry.[Results] In the CCl_4 injured group,the proliferation of L-02 cells was significantly declined,the levels of AST and ALT in cell culture medium were significantly increased,and the expressions of TLR4 and NFκBp65 in L-02 cells were increased; after the intervention of Saikosaponin d and Baicalin,1. 75 μg/mL group and 1. 5 μg/mL group had an effect of promoting the proliferation of L-02 cells and could reduce the levels of AST and ALT in the cell culture medium,and TLR4 and NFκBp65 proteins in L-02 cells also had a certain inhibitory effect. [Conclusions] The compatibility of Saikosapon d and Baicalin has a certain protective effect on CCl_4 injured L-02 cells. The protection mechanism may be related with its down-regulating TLR4-NFκB signaling pathway and reducing the inflammation.展开更多
Background and aim:Advanced liver fibrosis is a major risk for developing hepatocellular carcinoma(HCC)in chronic hepatitis C virus(HCV)patients.Direct-acting antivirals(DAAs)which are used for treating HCV infection,...Background and aim:Advanced liver fibrosis is a major risk for developing hepatocellular carcinoma(HCC)in chronic hepatitis C virus(HCV)patients.Direct-acting antivirals(DAAs)which are used for treating HCV infection,produce more than 90%cure rate but do not seem to diminish the rate of occurrence or recurrence of HCC.This study aimed to investigate the effect of DAAs sofosbuvir(SOF)and daclatasvir(DAC)on carbon tetrachloride(CCl4)-induced fibrotic changes in mice.Methods:Eighty adult male Swiss albino mice were randomly allocated into 8 groups(10 mice/group):normal control group,SOF group(receiving SOF 80 mg/kg body weight(BW),oral gavage,daily),DAC group(receiving DAC 30 mg/kg BW,oral gavage,daily),SOF t DAC group(receiving a combination of both,daily),CCl4 model group(receiving CCl42 mL/kg BW,intraperitoneal twice weekly)and three CCl4-intoxicated groups receiving either SOF or DAC or their combination.All CCl4 groups received CCl4 for 12 weeks followed by DAAs for another 12 weeks.Results:CCl4-induced a significant elevation of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and produced histopathological evidence of fibrosis and liver degeneration along with a significant increase(P0.001)of the proliferation markers(proliferating cell nuclear antigen(PCNA)and Ki-67),hepatic stellate cells(HSCs)activation markers(alpha-smooth muscle actin(a-SMA)and glial fibrillary acidic protein(GFAP)),fibrosis marker(matrix metalloproteinase-9(MMP-9))and proinflammatory cytokine(tumor necrosis factor-alpha(TNF-a)).CCl4-intoxicated mice treated with SOF,DAC,or their combination revealed a significant amelioration(P0.001)of CCl4-induced elevation of liver enzymes,fibrotic changes,and liver degeneration along with a significant attenuation(P0.001)of CCl4-induced upregulation of all tested markers.The effects of SOF,DAC,and their combination on liver enzymes were comparable while the effect of SOF t DAC combination on mitigating CCl4-induced upregulation of the proliferation and HSCs activation markers was significantly stronger than either SOF or DAC alone.As for MMP-9 and TNF-a,the effects of DAC and SOF t DAC combination were comparable and both were more significant than that of SOF alone.Conclusions:SOF and DAC may possess an antifibrotic effect that is independent of their role as antiviral agents against CCl4-induced liver injury.This might exclude the role of DAAs in early occurrence or accelerated recurrence of HCC through the progression of the HCV patients'pre-existing fibrosis.However,HCC patients treated with DAAs should be closely monitored with continuous HCC surveillance during and post-therapy.展开更多
基金Supported by a grant from the Institute of Virology, College of Life Sciences, Wuhan University
文摘AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.
基金Supported by National Natural Science Foundation of China and National Key Technologies R and D Program of the 11th five-year plan,No.2009ZX09501-015
文摘AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.
基金Supported by Project of Shaanxi Administration of Traditional Chinese Medicine(zy06)Special Project of Education Department of Shaanxi Provincial Government(12JK1016)Program of Shaanxi Provincial Department of Science and Technology(2013jk4023)
文摘[Objectives] To study the protection of compatibility of Saikosapon d and Baicalin on carbon tetrachloride( CCl_4) injured L-02 cells. [Methods] Normal human hepatocyte cell line L-02 cells were cultured in vitro,and CCl_4 was used to induce hepatocellular injury. Interventions were carried out with Saikosaponin d and Baicalin at different dosage. The proliferation of L-02 cells in each group was determined by methylthiazolyl tetrazolium( MTT) assay; the levels of AST and ALT in the culture supernatants were detected by enzyme-linked immunosorbent assay( ELISA); the expressions of TLR4 and NFκBp65 proteins in each group were determined by immunohistochemistry.[Results] In the CCl_4 injured group,the proliferation of L-02 cells was significantly declined,the levels of AST and ALT in cell culture medium were significantly increased,and the expressions of TLR4 and NFκBp65 in L-02 cells were increased; after the intervention of Saikosaponin d and Baicalin,1. 75 μg/mL group and 1. 5 μg/mL group had an effect of promoting the proliferation of L-02 cells and could reduce the levels of AST and ALT in the cell culture medium,and TLR4 and NFκBp65 proteins in L-02 cells also had a certain inhibitory effect. [Conclusions] The compatibility of Saikosapon d and Baicalin has a certain protective effect on CCl_4 injured L-02 cells. The protection mechanism may be related with its down-regulating TLR4-NFκB signaling pathway and reducing the inflammation.
文摘Background and aim:Advanced liver fibrosis is a major risk for developing hepatocellular carcinoma(HCC)in chronic hepatitis C virus(HCV)patients.Direct-acting antivirals(DAAs)which are used for treating HCV infection,produce more than 90%cure rate but do not seem to diminish the rate of occurrence or recurrence of HCC.This study aimed to investigate the effect of DAAs sofosbuvir(SOF)and daclatasvir(DAC)on carbon tetrachloride(CCl4)-induced fibrotic changes in mice.Methods:Eighty adult male Swiss albino mice were randomly allocated into 8 groups(10 mice/group):normal control group,SOF group(receiving SOF 80 mg/kg body weight(BW),oral gavage,daily),DAC group(receiving DAC 30 mg/kg BW,oral gavage,daily),SOF t DAC group(receiving a combination of both,daily),CCl4 model group(receiving CCl42 mL/kg BW,intraperitoneal twice weekly)and three CCl4-intoxicated groups receiving either SOF or DAC or their combination.All CCl4 groups received CCl4 for 12 weeks followed by DAAs for another 12 weeks.Results:CCl4-induced a significant elevation of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and produced histopathological evidence of fibrosis and liver degeneration along with a significant increase(P0.001)of the proliferation markers(proliferating cell nuclear antigen(PCNA)and Ki-67),hepatic stellate cells(HSCs)activation markers(alpha-smooth muscle actin(a-SMA)and glial fibrillary acidic protein(GFAP)),fibrosis marker(matrix metalloproteinase-9(MMP-9))and proinflammatory cytokine(tumor necrosis factor-alpha(TNF-a)).CCl4-intoxicated mice treated with SOF,DAC,or their combination revealed a significant amelioration(P0.001)of CCl4-induced elevation of liver enzymes,fibrotic changes,and liver degeneration along with a significant attenuation(P0.001)of CCl4-induced upregulation of all tested markers.The effects of SOF,DAC,and their combination on liver enzymes were comparable while the effect of SOF t DAC combination on mitigating CCl4-induced upregulation of the proliferation and HSCs activation markers was significantly stronger than either SOF or DAC alone.As for MMP-9 and TNF-a,the effects of DAC and SOF t DAC combination were comparable and both were more significant than that of SOF alone.Conclusions:SOF and DAC may possess an antifibrotic effect that is independent of their role as antiviral agents against CCl4-induced liver injury.This might exclude the role of DAAs in early occurrence or accelerated recurrence of HCC through the progression of the HCV patients'pre-existing fibrosis.However,HCC patients treated with DAAs should be closely monitored with continuous HCC surveillance during and post-therapy.
