title: As2 O3 combined with leflunomide prolongs heart xenograft survival via suppressing the response of Th1, Th2, and B cells in a rat model.
abstract: Xenotransplantation remits the severe shortage of human organs and tissues for transplantation, which is a problem that severely limits the application of transplantation to the treatment of human disease. However, severe immune rejection significantly limits the efficacy of xenotransplantation. In this study, we systematically investigated the immunosuppressive effect and mechanism of action of As2 O3 and leflunomide using a hamster-to-rat heart xenotransplantation model. We initially examined heart xenograft survival following As2 O3 and leflunomide treatment alone or combined treatment. We found that treatment with As2 O3 combined with leflunomide can significantly prolong the survival of heart xenograft by inhibiting Th1 and Th2 differentiation and reducing the production of IgG and IgM. Interestingly, As2 O3 and leflunomide showed low toxicity to the organs of the recipient. Taken together, these observations indicate that treatment with As2 O3 combined with leflunomide may be a promising immunosuppressive schedule for xenotransplantation.
authors.affiliation: The Second Department of Urinary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Jiao
authors.affiliation: Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Leng
authors.affiliation: Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Xia
authors.affiliation: Chenggong Hospital and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Hai-Qiao
authors.initials: HQ
authors.lastname: Wu
authors.affiliation: Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jin
authors.affiliation: Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Jia-Zhao
authors.initials: JZ
authors.lastname: Fu
authors.affiliation: Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, China.
authors.forename: Lian-Na
authors.initials: LN
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy Intravenous Admixture Service, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: The Second Department of Urinary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Ni
authors.affiliation: The Second Department of Urinary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Zhong-Quan
authors.initials: ZQ
authors.lastname: Qi
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D064593:Heterografts / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008297:Male; D010087:Oxides / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D001152:Arsenicals; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D010087:Oxides; D000077339:Leflunomide; D000077237:Arsenic Trioxide
keywords: As2O3; B cells; Th1/Th2; heart xenotransplantation; leflunomide