title: Novel action of 3,4-DAA ameliorating acute liver allograft injury.
abstract: The anti-allergic drug, N-(3,4-dimethoxycinnamonyl) anthranilic acid (3,4-DAA), is a synthetic anthranilic acid derivative that has been used therapeutically in Japan for many years. In this study, to investigate the effects of 3,4-DAA in allograft immunorejection model, liver orthotopic transplants were performed using inbred male Dark Agouti donors and Lewis rat recipients (allografts). The levels of indoleamine 2,3-dioxygenases (IDO) enzymic activities in five groups, allografts (control), dimethyl sulphoxide-treated group (vehicle control), 200 mg·kg(-1) ·day(-1) of 3,4-DAA-treated group and 200 mg·kg(-1) ·day(-1) of 3,4-DAA + 5 mg·ml(-1) of 1-methyl-D-tryptophan (1-MT)-treated group were confirmed by determination of L-kynurenine (L-Kyn) concentrations. The serum alanine aminotransferase levels in 3,4-DAA-treated rats significantly decreased compared with those in mock and control group, whereas treatment of 1-MT in allografts led to the opposite effect. Administration of 3,4-DAA reduced histological severity of allograft immunorejection, decreased serum levels of cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and raised serum levels of interleukin-10 (IL-10), suggesting that 3,4-DAA has both anti-inflammatory and anti-immunorejection properties through IDO in immune regulation and may therefore be useful in filling an unmet need, in the treatment of allograft immunorejection.
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital to Wenzhou Medical College, Rui'an, Zhejiang, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Sun
authors.forename: Ji-Guang
authors.initials: JG
authors.lastname: Ding
authors.forename: Ji-Fang
authors.initials: JF
authors.lastname: Sheng
authors.forename: Man-Hua
authors.initials: MH
authors.lastname: Zhu
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Zi-Ke
authors.initials: ZK
authors.lastname: Sheng
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tang
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology; D007371:Interferon-gamma; D016753:Interleukin-10 / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000293:injuries* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D062367:ortho-Aminobenzoates / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D062367:ortho-Aminobenzoates; D016753:Interleukin-10; D007371:Interferon-gamma; C012293:tranilast