Exploring the mechanism of isoniazid induced hypersensitivity reaction based on network toxicology

doi:10.3969/j.issn.1000-1565.2025.03.003

Abstract

Abstract: The molecular mechanism of hypersensitivity reactions induced by isoniazid in the treatment of pulmonary tuberculosis was studied using network toxicology methods. Through queries on ChEMBL, STITCH, GeneCards, and OMIM databases, 45 potential targets related to isoniazid and hypersensitivity reactions were identified. Further screening using STRING and Cytoscape software highlighted 11 core targets, including BCL2, CYP3A4, and DRD2. GO and KEGG pathway analysis showed through DAVID and FUMA databases that isoniazid induced hypersensitivity reactions are mainly related to the enrichment of substance metabolism and endocrine pathways. Molecular docking using Autodock confirmed that isoniazid can stably bind to core targets such as BCL2. The results of this study suggest that isoniazid may - DOI:10.3969/j.issn.1000-1565.2025.03.003基于网络毒理学探究异烟肼诱发超敏反应的作用机制张沛祥¹,田铄琪¹,王姚俊¹,武丽红²,梁建琴²,刘中成¹(1.河北大学药学院,河北省药物质量分析控制重点实验室,河北保定 071002;2. 中国人民解放军总医院第八医学中心,北京 100091)摘要:基于网络毒理学的方法研究异烟肼治疗肺结核时引发超敏反应的分子机制,通过ChEMBL、STITCH、GeneCards和OMIM数据库查询,获得了与异烟肼和超敏反应相关的45个潜在靶点.进一步利用STRING和Cytoscape软件进行筛选,突出了包括BCL2、CYP3A4和DRD2在内的11个核心靶点.GO和KEGG通路分析通过DAVID和FUMA数据库显示,异烟肼诱导超敏反应主要与物质代谢和内分泌通路的富集有关.使用Autodock进行的分子对接验证了异烟肼与BCL2等核心靶标可以稳定结合.本研究结果表明,异烟肼可能通过调节细胞代谢及钙信号通路、胆碱能突触通路等影响超敏反应的发生和发展.此研究不仅为理解异烟肼诱导超敏反应的分子机制提供了理论依据,还为找寻预防其不良反应的方法奠定了基础.关键词:异烟肼;网络毒理学;分子对接;超敏反应中图分类号:R593.21 文献标志码:A 文章编号:1000-1565(2025)03-0244-10Exploring the mechanism of isoniazid induced hypersensitivity reaction based on network toxicologyZHANG Peixiang¹, TIAN Shuoqi¹, WANG Yaojun¹, WU Lihong², LIANG Jianqin², LIU Zhongcheng¹(1. Key Laboratory of Drug Quality Analysis and Control, College of Pharmacy, Hebei University, Baoding 071002, China; 2. The Eighth Medical Center, the General Hospital of the Chinese Peoples Liberation Army, Beijing 100091,China)Abstract: The molecular mechanism of hypersensitivity reactions induced by isoniazid in the treatment of pulmonary tuberculosis was studied using network toxicology methods. Through queries on ChEMBL, STITCH, GeneCards, and OMIM databases, 45 potential targets related to isoniazid and hypersensitivity reactions were identified. Further screening using STRING and Cytoscape software highlighted 11 core targets, including BCL2, CYP3A4, and DRD2. GO and KEGG pathway analysis showed through DAVID and FUMA databases that isoniazid induced hypersensitivity reactions are mainly related to the enrichment of substance metabolism and endocrine pathways. Molecular docking using Autodock confirmed that isoniazid can stably bind to core targets such as BCL2. The results of this study suggest that isoniazid may - 收稿日期:2024-08-21;修回日期:2025-02-25 基金项目:河北省自然科学基金资助项目(H2023201026;H2022201035);首都卫生发展科研专项(2024-2-5094) 第一作者:张沛祥(1999—),男,河北大学在读硕士研究生,主要从事超敏反应相关信号通路研究.E-mail:zhangpeixiang@stumail.hbu.edu.cn 通信作者:刘中成(1979—),男,河北大学教授,主要从事基因工程制药、分子毒理学方向研究.E-mail:liuzc@hbu.edu.cn梁建琴(1966—),女,中国人民解放军总医院主任医师,主要从事结核药物不良反应的研究.E-mail:ljqbj309@163.com 第3期张沛祥等:基于网络毒理学探究异烟肼诱发超敏反应的作用机制河北大学学报(自然科学版) 第45卷affect the occurrence and development of hypersensitivity reactions by regulating cellular metabolism, calcium signaling pathways, cholinergic synaptic pathways, and other pathways. This study not only provides a theoretical basis for understanding the molecular mechanism of isoniazid induced hypersensitivity reactions, but also lays the foundation for finding methods to prevent its adverse reactions.

Key words: isoniazid, network toxicology, molecular docking, hypersensitivity

CLC Number:

R593.21

ZHANG Peixiang, TIAN Shuoqi, WANG Yaojun, WU Lihong, LIANG Jianqin, LIU Zhongcheng. Exploring the mechanism of isoniazid induced hypersensitivity reaction based on network toxicology[J]. Journal of Hebei University(Natural Science Edition), 2025, 45(3): 244-253.

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