Protective effects of PDTC on acute liver injury induced by ischemia reperfusion and endotoxiemia in rats

    WANG Lei, DOU Keª²Feng, YU Liª²Ping

    1Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi¬ðan 710033, China, 2Department of General Surgery, PLA Fifth Hospital, Yinchuan 750004, China, 3Department of Endocrinology, Second Affiliated Hospital, Ninxia Medical College, Yinchuan 750001, China

    ¡¾Abstract¡¿ AIM: To explore the protective effects of pyrrolidine dithiocarbamate (PDTC) on acute liver injury (ALI) induced by hepatic ischemia reperfusion and endotoxemia (HIRE) in rats. METHODS: Forty Wister rats were randomly divided into ischemia reperfusion and endotoxemia (HIRE) group (n=20), in which hepatic reperfusion was given after 60 min of ischemia by interruption of the arterial and portal venous blood supply to the left lobes and middle lobes of the liver and LPS (2.5 mg/kg) was injected via the dorsum vein of penis; HIRE+PDTC group (n=20), in which PDTC (120 mg/kg) was injected via the dorsum vein of penis before ischemia/reperfusion and endotoxemia. The NFª²¦ÊB activities were determined by EMSA, the expression levels of TNFª²¦Á were measured by immunohistochemistry (IH) and the serum levels of ALT were measured. RESULTS: NFª²¦ÊB was activated 0-12 h after reperfusion and reached its maximum 3 h after reperfusion in ischemia/ reperfusion endotoxemia group. The expression level of TNFª²¦Á increased markedly from 0 to 12 h and peaked 3 h after reperfusion in HIRE group. The serum levels of ALT increased significantly after reperfusion in ischemia/ reperfusion endotoxemia group. NFª²kB activities were significantly lower in PDTC treatment group than those in ischemia/ reperfusion endotoxemia group. The expression level of TNFª²¦Á was lowered markedly in HIRE+PDTC group as compared with that in HIRE group from 0 to 12 h after reperfusion. The serum levels of ALT decreased significantly after reperfusion in PDTC treatment group as compared with those in ischemia reperfusion endotoxemia group. CONCLUSION: PDTC protects against ALI by suppressing excessive NFª²¦ÊB activation and subsequent proinflammatory mediators during HIRE. ......