AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.METHODS:Livers of male Lewis rats were transplanted after 24 h of...AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100μmol/(h·kg),n=5 each) was continuously administered via the jugular vein.RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281U/L (mean±SE) in controls but to only 908_+187 U/L (P<0.05) in animals treated with 100μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatocytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7mol/L and 97±18μmol/L,but to only 20±3mol/L in untreated recipients.Furthermore, plasma glutathione disulfide (GSSG) increased to 7.5±1.0mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5mol/L vs 2.2±0.2mol/L).CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts.Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.展开更多
INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo ...INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.展开更多
本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,...本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,外周血胰岛素浓度增高、C 肽浓度减低。断流术前后,门脉和外周血胰岛素和 C 肽浓度、门静脉压力均无明显改变。提示肝硬化时出现的高胰岛素血症主要原因是肝细胞受损,胰岛素降解减少。但断流术能维持门脉血胰岛素的含量,有利于受损肝细胞的恢复和正常肝细胞的再生。展开更多
基金Supported in part by a grant from the Friedrich-Baur Stiftung,the Muenchener Medizinische Wochenschrift (MMW)the Deutsche Forschungsgemeinschaft (DFG Scha 857/1-1DFG FOR 440-717)
文摘AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100μmol/(h·kg),n=5 each) was continuously administered via the jugular vein.RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281U/L (mean±SE) in controls but to only 908_+187 U/L (P<0.05) in animals treated with 100μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatocytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7mol/L and 97±18μmol/L,but to only 20±3mol/L in untreated recipients.Furthermore, plasma glutathione disulfide (GSSG) increased to 7.5±1.0mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5mol/L vs 2.2±0.2mol/L).CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts.Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.
基金Supported by the Youth Science Grant of Jiangshu Province,No.BQ98048.
文摘INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.
文摘本实验用四氯化碳(简称 CCl_4)诱发大鼠肝硬化,观察硬化形成过程中门脉和外周血胰岛素的变化,以及门奇静脉断流术后门脉和外周血中胰岛素变化情况。结果发现,随肝硬化程度加重,门静脉压力逐渐增高,门脉血中胰岛素和 C 肽浓度逐渐降低,外周血胰岛素浓度增高、C 肽浓度减低。断流术前后,门脉和外周血胰岛素和 C 肽浓度、门静脉压力均无明显改变。提示肝硬化时出现的高胰岛素血症主要原因是肝细胞受损,胰岛素降解减少。但断流术能维持门脉血胰岛素的含量,有利于受损肝细胞的恢复和正常肝细胞的再生。
