OBJECTIVE: To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation. METHODS: Brown Norway (BW) recipient rats of orthotopic liver transplantation (OLT) were divided into three groups, Group A receiving isografting (with BW rats as donor), Group B receiving allografting (with Lewis rats as donor), Group C receiving allografting and emodin treatment (50 mg/kg daily). They were sacrificed on day 7 of post-transplantation, and their hepatic histology, plasma cytokine levels, and T-cell subset expression were detected. RESULTS: Compared with those in Group A, rats: in Group B exhibited severe allograft rejection with a rejection activity index (RAI) of 7.67+/-0.98, extensive hepatocellular apoptosis with an apoptosis index (AI) of 35.83+/-2.32, and elevated plasma levels of interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), CD4(+) and CD4 CD4(+)/CD8(+) ratio. However, recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis, as well as a decrease in plasma levels of IL-2, TNF-alpha, CD4(+) and CD4(+)/CD8(+) ratio, but elevated levels of IL-10 as compared with the allograft group. CONCLUSION: Post-OLT acute rejection could be attenuated by emodin, its mechanism of action may be associated with protecting hepatocytes from apoptosis, polarizing the Th 1 paradigm to Th2, and inhibiting the proliferation of CD4(+) T cell in plasma.
OBJECTIVE: To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation. METHODS: Brown Norway (BW) recipient rats of orthotopic liver transplantation (OLT) were divided into three groups, Group A receiving isografting (with BW rats as donor), Group B receiving allografting (with Lewis rats as donor), Group C receiving allografting and emodin treatment (50 mg/kg daily). They were sacrificed on day 7 of post-transplantation, and their hepatic histology, plasma cytokine levels, and T-cell subset expression were detected. RESULTS: Compared with those in Group A, rats: in Group B exhibited severe allograft rejection with a rejection activity index (RAI) of 7.67+/-0.98, extensive hepatocellular apoptosis with an apoptosis index (AI) of 35.83+/-2.32, and elevated plasma levels of interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), CD4(+) and CD4CD4(+)/CD8(+) ratio. However, recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis, as well as a decrease in plasma levels of IL-2, TNF-alpha, CD4(+) and CD4(+)/CD8(+) ratio, but elevated levels of IL-10 as compared with the allograft group. CONCLUSION: Post-OLT acute rejection could be attenuated by emodin, its mechanism of action may be associated with protecting hepatocytes from apoptosis, polarizing the Th 1 paradigm to Th2, and inhibiting the proliferation of CD4(+) T cell in plasma.
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