Effect of emodin in suppressing acute rejection following liver allograft transplantation in rats.
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.


CONCLUSIONS
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.
Lin
Sheng-zhang
SZ
Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang (310003), China. zysxswzsz@zju.edu.cn
Tong
Hong-fei
HF
Chen
Kang-jie
KJ
Jing
He
H
Yang
Xiao
X
Zheng
Shu-sen
SS
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D004642:Emodin / Q000494:pharmacology* / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D016031:Liver Transplantation / Q000276:immunology / Q000534:rehabilitation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
D016207:Cytokines; D007166:Immunosuppressive Agents; D004642:Emodin
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