title: Emodin prolongs recipient survival time after orthotopic liver transplantation in rats by polarizing the Th1/Th2 paradigm to Th2.
abstract: Advances in immunosuppressive drugs have improved the short-term survival of liver transplantation. However, drug toxicities have been a serious problem in patients after long-term administration. Therefore, it is necessary to develop a novel immunosuppressant with low-toxicity. We investigated the immunosuppressive effects of Emodin on acute graft rejection following liver transplantation in rats. The recipient rats of orthotopic liver transplantation were divided into groups as follows: isograft+NS group, allograft+NS group, and allograft+emodin group. The survival time of the recipients in each group was recorded. Histopathological changes in the liver, as well as serum concentrations of IL-2, TNF-α, and IL-10 and their expressions in liver tissue were determined. Our results showed that Emodin treatment prolonged liver allograft survival time and inhibited histopathologic changes of acute graft rejection. The rejection activity index in groups isograft+NS, allograft+NS, and allograft+emodin were 1.52 ± 0.37, 6.95 ± 0.75, and 4.23 ± 0.51, respectively (P < 0.01, isograft+NS group vs. allograft+emodin group and allograft+NS group vs. allograft+emodin group). The serum levels of IL-2 and TNF-α were down-regulated but that of IL-10 was up-regulated by Emodin. Serum levels of IL-2 and TNF-α were higher in allograft+NS group than the allograft+emodin group, but that of IL-10 showed opposite effects (P < 0.05 or 0.01). Changes in the expression of these cytokines in transplanted liver tissue were consistent with changes in serum concentrations. These results demonstrate that Emodin has therapeutic potentials for alleviating acute rejection following liver transplantation in rats and prolonging liver allograft survival. The mechanisms underlying this effect may be associated with polarizing the Th1/Th2 paradigm to Th2.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Tong
authors.forename: Kangjie
authors.initials: K
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Huayong
authors.initials: H
authors.lastname: Wu
authors.forename: Haiduo
authors.initials: H
authors.lastname: Lin
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Ni
authors.forename: Shengzhang
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004642:Emodin / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D016031:Liver Transplantation; D008297:Male; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma; D004642:Emodin