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
[Objectives]To study the protective effect of Ershiwuwei Songshi Pills on chronic liver injury induced by carbon tetrachloride(CCL4)in rats before and after the modification conforming to the compatibility theory of T...[Objectives]To study the protective effect of Ershiwuwei Songshi Pills on chronic liver injury induced by carbon tetrachloride(CCL4)in rats before and after the modification conforming to the compatibility theory of Tibetan medicine,and to explore its action mechanism.[Methods]Male Wistar rats were randomly divided into the blank control group,model group,Hugan tablets group(0.490 g/kg),Ershiwuwei Songshi Pills group(0.117 g/kg),and Modified Ershiwuwei Songshi Pills group(removing cinnabaris,Aristolochia contorta,and Aconitum naviculare,0.105 g/kg).Except the blank group,the remaining groups were injected subcutaneously with 20%carbon tetrachloride olive oil solution every 3 d,and modeled for 6 weeks.During this time,intragastrically administered corresponding drugs.Six weeks later,blood was taken from the femoral artery,and the rats were killed through dislocating the cervical spine,the liver was taken,and the content of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)was determined.Then,liver fibrosis indicators tumor necrosis factor-α(TNF-α),nuclear factor-κB(NF-κB),interleukin-6(IL-6)and interleukin-1β(IL-1β)were detected by immunohistochemical method.[Results]Compared with the model group,the pathological map of the liver section showed that liver injury was improved in each administration group.The serum ALT and AST contents in rats of each administration group were significantly reduced(P<0.05),and the protein expressions of NF-κB,TNF-α,IL-1βand IL-6 in liver tissue were also reduced by varying degrees(P<0.05).[Conclusions]Ershiwuwei Songshi Pills and its modification group have a protective effect on liver injury induced by carbon tetrachloride.The modified prescription conforms to the compatibility rules of Tibetan medicine.The mechanism may be related to reducing the damage caused by inflammatory factors through regulating the role of inflammatory signaling pathway.Thus,it can be used as a reference for future optimization proposals.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 the Fundamental Research Funds for the Central Universities(2018NZD19)Systematic Study and Industrial Demonstration of Prevention and Treatment of Liver Diseases with Tibetan Medicines of the Qinghai-Tibet PlateauInnovating Research Program of Postgraduates of Southwest Minzu University in 2018(CX2018SZ81).
文摘[Objectives]To study the protective effect of Ershiwuwei Songshi Pills on chronic liver injury induced by carbon tetrachloride(CCL4)in rats before and after the modification conforming to the compatibility theory of Tibetan medicine,and to explore its action mechanism.[Methods]Male Wistar rats were randomly divided into the blank control group,model group,Hugan tablets group(0.490 g/kg),Ershiwuwei Songshi Pills group(0.117 g/kg),and Modified Ershiwuwei Songshi Pills group(removing cinnabaris,Aristolochia contorta,and Aconitum naviculare,0.105 g/kg).Except the blank group,the remaining groups were injected subcutaneously with 20%carbon tetrachloride olive oil solution every 3 d,and modeled for 6 weeks.During this time,intragastrically administered corresponding drugs.Six weeks later,blood was taken from the femoral artery,and the rats were killed through dislocating the cervical spine,the liver was taken,and the content of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)was determined.Then,liver fibrosis indicators tumor necrosis factor-α(TNF-α),nuclear factor-κB(NF-κB),interleukin-6(IL-6)and interleukin-1β(IL-1β)were detected by immunohistochemical method.[Results]Compared with the model group,the pathological map of the liver section showed that liver injury was improved in each administration group.The serum ALT and AST contents in rats of each administration group were significantly reduced(P<0.05),and the protein expressions of NF-κB,TNF-α,IL-1βand IL-6 in liver tissue were also reduced by varying degrees(P<0.05).[Conclusions]Ershiwuwei Songshi Pills and its modification group have a protective effect on liver injury induced by carbon tetrachloride.The modified prescription conforms to the compatibility rules of Tibetan medicine.The mechanism may be related to reducing the damage caused by inflammatory factors through regulating the role of inflammatory signaling pathway.Thus,it can be used as a reference for future optimization proposals.
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.
