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Novel action of 3,4‐DAA ameliorating acute liver allograft injury
Author(s) -
Sun QingFeng,
Ding JiGuang,
Sheng JiFang,
Zhu ManHua,
Li JunJie,
Sheng ZiKe,
Tang XiaoFeng
Publication year - 2011
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1805
Subject(s) - anthranilic acid , kynurenine , medicine , tumor necrosis factor alpha , immune system , indoleamine 2,3 dioxygenase , pharmacology , necrosis , tryptophan , immunology , chemistry , biochemistry , amino acid
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. Copyright © 2011 John Wiley & Sons, Ltd.