Indoleamine 2, 3-dioxygenase 1 aggravates acetaminophen-induced acute liver failure by triggering excess nitroxidative stress and iron accumulation

Li, Yunjia; Song, Yu; Deng, Guanghui; Tan, Qinxiang; Xu, Shu; Yang, Menghan; Shi, Hao; Hong, Mu-Keng; Ye, Haixin; Wu, Chaofeng; Ma, Shuoyi; Huang, Huacong; Zhang, Yanhong; Zeng, Zhiyun; Wang, Ming; Chen, Yuyao; Wang, Yunqing; Ma, Jun; Li, Juan; Gao, Lei

doi:10.1016/j.freeradbiomed.2021.07.008

Cited by 4 publications

(1 citation statement)

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“…IDO1 is associated with many disorders of immune function, including cancer, HBV infection, allergy, and autoimmune diseases (Ito et al, 2014;Liu et al, 2018;Heidari et al, 2022). Inhibition of IDO1 expression can induce immune-mediated liver injury (Affolter et al, 2019), but it has also been shown that IDO1 deficiency or inhibition can weaken acetaminophen or concanavalin A-induced liver injury (Li et al, 2021b). ICAM1, a cell surface glycoprotein and adhesion receptor, is expressed at a low basic level in immune, endothelial, and epithelial cells, but upregulated in Frontiers in Chemistry frontiersin.org response to inflammatory stimulation, which promotes the recruitment and activation of white blood cells from circulation to inflammatory sites (Bui et al, 2020), playing an important role in the progress of diseases including tumors, hepatitis, colitis, and cardiovascular and cerebrovascular diseases (Chen et al, 2013;Hoke et al, 2015;Zhu et al, 2015;West et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

A gene expression profile-based approach to screen the occurrence and predisposed host characteristics of drug-induced liver injury: a case study of Psoralea corylifolia Linn

Zhang,

Li,

Wang

et al. 2023

Front. Chem.

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Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

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