AIM: To investigate the effect of pyrrolidine dithiocarbamate (PDTC), a novel nuclear factor-kappaB (NF-kappaB) inhibitor, on expression of multiple inflammatory mediators and neutrophilic inflammation of cold preserved grafts after rat liver transplantation and its significance. METHODS: Orthotopic liver transplantation (OLT) was performed after 24 h of cold storage using University of Wisconsin solution with varied concentrations of PDTC. We determined the time course of NF-kappaB activation and expression of multiple inflammatory signals, such as tumor necrosis factor-alpha (TNF-alpha), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) by ELISA methods. Serum alanine aminotransferase (ALT), intrahepatic myeloperoxidase (MPO)/WBC (a measure of neutrophil accumulation) and Mac-1 expression (a measure of circulating neutrophil activity) were also evaluated. RESULTS: PDTC decreased NF-kappaB activation induced by prolonged cold preservation in a dose dependent manner (from 20 mmol/L to 60 mmol/L), diminished TNF-alpha, CINC, ICAM-1 proteins in the grafts, and reduced the expression of increases in plasma TNF-alpha levels induced by prolonged cold preservation. Neutrophilic inflammation of the graft was significantly suppressed after preservation with PDTC (P<0.05). The total neutrophil accumulation in PDTC (40 mmol/L) group (7.04+/-0.97) was markedly reduced compared to control group (14.07+/-1.31) (P<0.05). Mac-1 expression was significantly reduced in PDTC (40 mmol/L) group (181+/-11.3%) compared with the control group (281+/-13.2%) (P<0.05) at 6 h after reperfusion. Furthermore, PDTC inhibited the increased serum ALT levels after liver transplantation. CONCLUSION: PDTC can inhibit B NF-kappaB activation and expression of the inflammatory mediators, which are associated with improved graft viability via inhibiting intrahepatic neutrophilic inflammation. Our study suggests that a therapeutic strategy directed at inhibition of NF-kappaB activation in the transplanted liver might be effective in reducing intrahepatic neutrophilic inflammation, and would be beneficial to cold preserved grafts.
AIM: To investigate the effect of pyrrolidine dithiocarbamate (PDTC), a novel nuclear factor-kappaB (NF-kappaB) inhibitor, on expression of multiple inflammatory mediators and neutrophilic inflammation of cold preserved grafts after rat liver transplantation and its significance. METHODS: Orthotopic liver transplantation (OLT) was performed after 24 h of cold storage using University of Wisconsin solution with varied concentrations of PDTC. We determined the time course of NF-kappaB activation and expression of multiple inflammatory signals, such as tumor necrosis factor-alpha (TNF-alpha), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) by ELISA methods. Serum alanine aminotransferase (ALT), intrahepaticmyeloperoxidase (MPO)/WBC (a measure of neutrophil accumulation) and Mac-1 expression (a measure of circulating neutrophil activity) were also evaluated. RESULTS:PDTC decreased NF-kappaB activation induced by prolonged cold preservation in a dose dependent manner (from 20 mmol/L to 60 mmol/L), diminished TNF-alpha, CINC, ICAM-1 proteins in the grafts, and reduced the expression of increases in plasma TNF-alpha levels induced by prolonged cold preservation. Neutrophilic inflammation of the graft was significantly suppressed after preservation with PDTC (P<0.05). The total neutrophil accumulation in PDTC (40 mmol/L) group (7.04+/-0.97) was markedly reduced compared to control group (14.07+/-1.31) (P<0.05). Mac-1 expression was significantly reduced in PDTC (40 mmol/L) group (181+/-11.3%) compared with the control group (281+/-13.2%) (P<0.05) at 6 h after reperfusion. Furthermore, PDTC inhibited the increased serum ALT levels after liver transplantation. CONCLUSION:PDTC can inhibit B NF-kappaB activation and expression of the inflammatory mediators, which are associated with improved graft viability via inhibiting intrahepatic neutrophilic inflammation. Our study suggests that a therapeutic strategy directed at inhibition of NF-kappaB activation in the transplanted liver might be effective in reducing intrahepatic neutrophilic inflammation, and would be beneficial to cold preserved grafts.
Authors: S Arii; K Monden; Y Adachi; W Zhang; H Higashitsuji; M Furutani; M Mise; S Fujita; T Nakamura; M Imamura Journal: Transplantation Date: 1994-11-27 Impact factor: 4.939
Authors: S Natori; M Selzner; K L Valentino; L C Fritz; A Srinivasan; P A Clavien; G J Gores Journal: Transplantation Date: 1999-07-15 Impact factor: 4.939
Authors: R Ricciardi; R D Kim; T P McDade; R A Perugini; T M Veal; S H Quarfordt; M P Callery; R S Chari; W C Meyers Journal: J Surg Res Date: 2000-09 Impact factor: 2.192