留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

应中央军委要求,2022年9月起,《药学实践杂志》将更名为《药学实践与服务》,双月刊,正文96页;2023年1月起,拟出版月刊,正文64页,数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿!

异烟肼致肝损伤发病机制的研究进展

王玉鹏 鲍婕

王玉鹏, 鲍婕. 异烟肼致肝损伤发病机制的研究进展[J]. 药学实践与服务, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
引用本文: 王玉鹏, 鲍婕. 异烟肼致肝损伤发病机制的研究进展[J]. 药学实践与服务, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
WANG Yupeng, BAO Jie. Research progress on the pathogenesis of isoniazid induced liver injury[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
Citation: WANG Yupeng, BAO Jie. Research progress on the pathogenesis of isoniazid induced liver injury[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001

异烟肼致肝损伤发病机制的研究进展

doi: 10.3969/j.issn.1006-0111.2019.04.001

Research progress on the pathogenesis of isoniazid induced liver injury

  • 摘要: 异烟肼(isoniazid,INH)是化学预防、治疗结核病的重要药物之一,是四大一线抗结核病药物中至关重要的首选药物。一系列研究表明异烟肼具有肝脏毒性,而其肝损伤机制仍未阐明。对异烟肼肝毒性与其代谢物、线粒体功能障碍、氧化应激、脂质过氧化的关系进行阐述。综述现阶段潜在的异烟肼肝毒性机制研究,为后续深入揭示该方面研究工作提供参考。
  • [1] RAMAPPA V,AITHAL G P.Hepatotoxicity related to anti-tuberculosis drugs:mechanisms and management[J].J Clin Exp Hepatol,2013,3(1):37-49.
    [2] Williams C.Global tuberculosis control:WHO report 2011[J].Austral New Zeal J Publ Health,2012,36(5):497-498.
    [3] DEVARBHAVI H,DIERKHISING R,KREMERS W K. Antituberculosis therapy drug-induced liver injury and acute liver failure[J].Hepatology,2010,52(2):798-799.
    [4] PARK W B,KIM W,LEE K L,et al.Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis[J].J Infect,2010,61(4):323-329.
    [5] YEW WW,LEUNG C C.Antituberculosis drugs and hepatotoxicity[J].Am J Respir Crit Care Med,2007,175(8):858.
    [6] WANG P C,PRADHAN K,ZHONG X B,et al.Isoniazid metabolism and hepatotoxicity[J].Acta Pharm Sin B,2016,6(5):384-392.
    [7] METUSHI I G,CAI P,ZHU X,et al.A fresh look at the mechanism of isoniazid-induced hepatotoxicity[J].Clin Pharmacol Ther,2011,89(6):911-914.
    [8] MITCHELL J R,ZIMMERMAN H J,ISHAK K G,et al.Isoniazid liver injury:clinical spectrum,pathology,and probable pathogenesis[J].Ann Intern Med,1976,84(2):181-192.
    [9] INGAWALE D K,MANDLIK S K,NAIK S R.Models ofhepatotoxicity and the underlying cellular,biochemical and immunological mechanism(s):A critical discussion[J].Environ Toxicol Pharmacol,2014,37(1):118-133.
    [10] HASSAN H M,HONGLI G,YOUSEF B A,et al.Hepatotoxicity mechanisms of isoniazid:A mini-review[J].J Appl Toxicol,2015,35(12):1427-1432.
    [11] BALÓ J.Role of hydrazine incarcinogenesis[J].Adv Cancer Res,1979,30:151-164.
    [12] TIMPERIO A M,RINALDUCCI S,ZOLLA L.Hydrazide derivatives produce active oxygen species as hydrazine[J].Bioorg Chem,2005,33(6):459-469.
    [13] PERWITASARI D A,ATTHOBARI J,WILFFERT B. Pharmacogenetics of isoniazid-induced hepatotoxicity[J].Drug Metab Rev,2015,47(2):222-228.
    [14] GARROD S,BOLLARD M E,NICHOLLS A W,et al.Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity in the rat[J].Chem Res Toxicol,2005,18(2):115-122.
    [15] BANDO K,KUNIMATSU T,JUN S K,et al.GC-MS-based metabolomics reveals mechanism of action for hydrazine induced hepatotoxicity in rats[J].J Appl Toxicol,2011,31(6):524-535.
    [16] OLTHOF E,TOSTMANN A,PETERS W H,et al.Hydrazine-induced liver toxicity is enhanced by glutathione depletion but is not mediated by oxidative stress in HepG2 cells[J].Int J Antimicrob Agents,2009,34(4):385-386.
    [17] BOELSTERLI U A,LEE KK.Mechanisms of isoniazid-induced idiosyncratic liver injury:emerging role of mitochondrial stress[J].J Gastroenterol Hepatol,2014,29(4):678-687.
    [18] PESSAYRE D,MANSOURI A,BERSON A,et al.Mitochondrial involvement in drug-induced liverinjury[J].Handb Exp Pharmacol,2010(196):311-365.
    [19] LEE KK,BOELSTERLI U A.By passing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes[J].Redox Biol,2014,2:599-609.
    [20] 张炜.抗结核药物致小鼠肝细胞线粒体损伤的研究[D].河北唐山:华北煤炭医学院,2010:22-26
    [21] BHADAURIA S,SINGH G,SINHA N,et al.Isoniazid induces oxidative stress,mitochondrial dysfunction and apoptosis in HepG2 cells[J].Cell Mol Biol(Noisy-le-grand),2007,53(1):102-114.
    [22] BHADAURIA S,MISHRA R,KANCHAN R,et al.Isoniazid-induced apoptosis in HepG2 cells:generation of oxidative stress and Bcl-2 down-regulation[J].Toxicol Mech Methods,2010,20(5):242-251.
    [23] 郭瑶雪,邓晔,李春,等.异烟肼致线粒体损伤引起药物性肝损伤研究进展[J].中国临床药理学与治疗学,2015,20(3):356-360.
    [24] WU Z R,BAI Z T,SUN Y,et al.Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin[J].Bioorg Med Chem Lett,2015,25(22):5424-5426.
    [25] CHEN X,XU J,ZHANG C,et al.The protective effects ofursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice[J].Eur J Pharmacol,2011,659(1):53-60.
    [26] CEDERBAUM A.Nrf2 and antioxidant Defense against CYP2E1toxicity[J].Expert Opin Drug Metab Toxicol,2009,5(10):1223-1244.
    [27] HASSAN H M,GUO H L,YOUSEF B A,et al.Role of inflammatory and oxidative stress,cytochrome P4502E1,and bile acid disturbance in rat liver injury induced by isoniazid and lipopolysaccharide cotreatment[J].Antimicrob Agents Chemother,2016,60(9):5285-5293.
    [28] CHOWDHURY A,SANTRA A,BHATTACHARJEE K,et al. Mitochondrial oxidative stress and permeability transition inisoniazid and rifampicin induced liver injury in mice[J].J Hepatol,2006,45(1):117-126.
    [29] YUE J,PENG R X,YANG J,et al.CYP2E1 mediatedisoniazid-induced hepatotoxicity in rats[J].Acta Pharmacol Sin,2004,25(5):699-704.
    [30] SHENG Y J,WU G,HE H Y,et al.The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs:A meta-analysis[J].Infect Genet Evol,2014,24:34-40.
    [31] CHEN YY,XUE P,HOU Y Y,et al.Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes[J].Toxicol Appl Pharmacol,2013,273(3):435-441.
    [32] SAAD E I,EL-GOWILLY S M,SHERHAA M O,et al.Role of oxidative stress and nitric oxide in the protective effects of alpha-lipoic acid and aminoguanidine against isoniazid-rifampicin-induced hepatotoxicity in rats[J].Food Chem Toxicol,2010,48(7):1869-1875.
    [33] PAL R,RANA S V,VAIPHEI K,et al.Isoniazid-rifampicin induced lipid changes in rats[J].Clin Chim Acta,2008,389(1-2):55-60.
    [34] PALANISAMY N,MANIAN S.Protective effects of Asparagusracemosus on oxidative damage in isoniazid-induced hepatotoxic rats:An in vivo study[J].Toxicol Ind Health,2012,28(3):238-244.
    [35] SHIH T Y,YOUNG T H,LEE H S,et al.Protective effects of kaempferol on isoniazid- and rifampicin-induced hepatotoxicity[J].AAPS J,2013,15(3):753-762.
    [36] DONG Y Z,HUANG J C,LIN X,et al.Hepatoprotective effects of Yulangsan polysaccharide against isoniazid and rifampicin-induced liver injury in mice[J].J Ethnopharmacol,2014,152(1):201-206.
    [37] LI F,LU J,CHENG J,et al.Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy[J].Nat Med,2013,19(4):418-420.
    [38] SACHAR M,ANDERSON K E,MA X C.Protoporphyrin IX:the good,the bad,and the ugly[J].J Pharmacol Exp Ther,2016,356(2):267-275.
    [39] FONTANA A O,PIFFARETTI D,MARCHI F,et al.Epithelial growth factor receptor expression influences 5-ALA induced glioblastoma fluorescence[J].J Neurooncol,2017,133(3):497-507.
    [40] LYOUMI S,LEFEBVRE T,KARIM Z,et al.PXR-ALAS1:a key regulatory pathway in liver toxicity induced byisoniazid-rifampicin antituberculosis treatment[J].Clin Res Hepatol Gastroenterol,2013,37(5):439-441.
    [41] SACHAR M,LI F,LIU K,et al.Chronic treatment with isoniazid causes protoporphyrin IX accumulation in mouse liver[J].Chem Res Toxicol,2016,29(8):1293-1297.
    [42] JAMES L,ROBERTS D.Isoniazid hepatotoxicity:progress in understanding the immunologic component[J].Hepatology,2014,59(3):746-748.
    [43] METUSHI I G,UETRECHT J.Isoniazid-induced liver injury and immune response in mice[J].J Immunotoxicol,2014,11(4):383-392.
    [44] SALAZAR-PÓRAMO M,RUBIN R L,GARCÍA-DE LA TORRE I.Systemic lupuserythematosus induced by isoniazid[J].Ann Rheum Dis,1992,51(9):1085-1087.
    [45] UETRECHT J.Immunoallergic drug-induced liver injury in humans[J].Semin Liver Dis,2009,29(4):383-392.
    [46] METUSHI I G,SANDERS C,ACUTE LIVER STUDY GROUP,et al.Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure[J].Hepatology,2014,59(3):1084-1093.
    [47] VIGNATI L,TURLIZZI E,MONACI S,et al.An in vitro approach to detect metabolite toxicity due to CYP3A4-dependent bioactivation of xenobiotics[J].Toxicology,2005,216(2-3):154-167.
    [48] 张志华.异烟肼和利福平合用致肝细胞毒性及药物保护机制探讨[D].石家庄:河北医科大学,2009:62-64.
    [49] WEN X,WANG J S,NEUVONEN P J,et al.Isoniazid is a mechanism-based inhibitor of cytochrome P4501A2,2A6,2C19 and 3A4 isoforms in human liver microsomes[J].Eur J Clin Pharmacol,2002,57(11):799-804.
    [50] LIU K,LI F,LU J,et al.Role of CYP3A inisoniazid metabolism in vivo[J].Drug Metab Pharmacokinet,2014,29(2):219-222.
    [51] ORTEGA-ALONSO A,STEPHENS C,LUCENA M I,et al.Case characterization,clinical features and risk factors in drug-induced liver injury[J].Int J Mol Sci,2016,17(5):E714.
    [52] 朱家莲,龚奕,彭文兴.异烟肼/利福平致肝损伤的生物标志物研究进展[J].中国医院药学杂志,2018,38(22):2380-2383.
    [53] TASDUQ S A,PEERZADA K,KOUL S,et al.Biochemical manifestations of anti-tuberculosis drugs induced hepatotoxicity and the effect of silymarin[J].Hepatol Res,2005,31(3):132-135.
    [54] WU Z R,BAI Z T,SUN Y,et al.Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin[J].Bioorg Med Chem Lett,2015,25(22):5424-5426.
  • [1] 李想, 陆鸿远, 张明玉, 高欢, 姚东, 许子华.  米格列醇激活UCP1介导棕色脂肪对冷暴露小鼠损伤的研究 . 药学实践与服务, 2025, 43(1): 1-6. doi: 10.12206/j.issn.2097-2024.202404005
    [2] 陈莹, 许子华, 胡北, 崔亚玲, 高欢, 吴琼.  通便灵胶囊治疗便秘的药效与机制研究 . 药学实践与服务, 2025, 43(1): 1-7. doi: 10.12206/j.issn.2097-2024.202404008
    [3] 张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英.  二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
    [4] 景凯, 杨慈荣, 张圳, 臧艺蓓, 刘霞.  黄芪甲苷衍生物治疗慢性心力衰竭小鼠的药效评价及作用机制研究 . 药学实践与服务, 2024, 42(5): 190-197. doi: 10.12206/j.issn.2097-2024.202310004
    [5] 李清, 郭宜银, 陈颖, 瞿发林, 董文燊, 戈煜.  夜宁胶囊对小鼠镇静催眠作用及其机制的研究 . 药学实践与服务, 2024, 42(8): 346-349. doi: 10.12206/j.issn.2097-2024.202211047
    [6] 段禹, 刘爱军.  活血化瘀法治疗血管性痴呆的研究进展 . 药学实践与服务, 2024, 42(): 1-6. doi: 10.12206/j.issn.2097-2024.202408045
    [7] 刘汝雄, 杨万镇, 涂杰, 盛春泉.  铁死亡调控蛋白GPX4的小分子抑制剂研究进展 . 药学实践与服务, 2024, 42(9): 375-378. doi: 10.12206/j.issn.2097-2024.202312075
    [8] 顾佳钰, 胡馨儿, 王晓飞, 张颖, 张海, 曹岩.  侧流免疫层析定量检测方法的研究进展 . 药学实践与服务, 2024, 42(7): 273-277, 284. doi: 10.12206/j.issn.2097-2024.202307037
    [9] 马兹芬, 许维恒, 金煜翔, 薛磊.  食管癌的靶向治疗与免疫治疗研究进展 . 药学实践与服务, 2024, 42(6): 231-237. doi: 10.12206/j.issn.2097-2024.202306008
    [10] 冯婷婷, 张景翔, 王彦, 许维恒, 张俊平.  ANXA3基因及蛋白的研究进展 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202309023
    [11] 杨凤艳, 张月, 陈恩贤, 缪雪蓉, 魏凯.  瑞马唑仑临床应用研究进展 . 药学实践与服务, 2024, 42(9): 365-374. doi: 10.12206/j.issn.2097-2024.202405026
    [12] 张林晨, 张小琴, 张俊平.  山楂酸药理作用的研究进展 . 药学实践与服务, 2024, 42(5): 185-189. doi: 10.12206/j.issn.2097-2024.202307052
    [13] 修建平, 杨朝爱, 刘禧澳, 潘乾禹, 韦广旭, 王卫星.  全反式维甲酸对肝星状细胞活化及氧化应激的作用和机制探索 . 药学实践与服务, 2024, 42(7): 291-296. doi: 10.12206/j.issn.2097-2024.202312054
    [14] 宋泽成, 陈林林, 鲁仁义, 刘梦肖, 王彦.  脓毒症治疗的研究进展 . 药学实践与服务, 2024, 42(11): 457-460, 502. doi: 10.12206/j.issn.2097-2024.202405059
    [15] 张岩, 李炎君, 刘家荟, 邓娇, 原苑, 张敬一.  药物性肝损伤不良反应分析 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404034
    [16] 姜涛, 徐卫凡, 蒋益萍, 夏天爽, 辛海量.  巴戟天丸组方对Aβ损伤成骨细胞的作用及基于网络药理学的机制研究 . 药学实践与服务, 2024, 42(7): 285-290, 296. doi: 10.12206/j.issn.2097-2024.202305011
    [17] 杨念, 张博乐, 张俊霞, 张振强.  一种中药组合物对ANIT诱导的小鼠胆汁淤积肝损伤的保护作用研究 . 药学实践与服务, 2024, 42(12): 508-511, 519. doi: 10.12206/j.issn.2097-2024.202305008
    [18] 钱淑雨, 李铁军.  耐碳青霉烯类肠杆菌耐药机制的研究进展 . 药学实践与服务, 2024, 42(10): 419-425. doi: 10.12206/j.issn.2097-2024.202405005
    [19] 徐飞, 陈瑾, 鲁育含, 李志勇.  肠道菌群参与糖尿病肾病的机制研究进展 . 药学实践与服务, 2024, 42(5): 181-184, 197. doi: 10.12206/j.issn.2097-2024.202312023
    [20] 王耀振, 徐灿, 吕顺莉, 田泾, 张东炜.  钾离子竞争性酸阻滞剂的药学特征研究进展 . 药学实践与服务, 2024, 42(7): 278-284. doi: 10.12206/j.issn.2097-2024.202306040
  • 加载中
计量
  • 文章访问数:  5822
  • HTML全文浏览量:  1043
  • PDF下载量:  814
  • 被引次数: 0
出版历程
  • 收稿日期:  2018-12-20
  • 修回日期:  2019-03-28

异烟肼致肝损伤发病机制的研究进展

doi: 10.3969/j.issn.1006-0111.2019.04.001

摘要: 异烟肼(isoniazid,INH)是化学预防、治疗结核病的重要药物之一,是四大一线抗结核病药物中至关重要的首选药物。一系列研究表明异烟肼具有肝脏毒性,而其肝损伤机制仍未阐明。对异烟肼肝毒性与其代谢物、线粒体功能障碍、氧化应激、脂质过氧化的关系进行阐述。综述现阶段潜在的异烟肼肝毒性机制研究,为后续深入揭示该方面研究工作提供参考。

English Abstract

王玉鹏, 鲍婕. 异烟肼致肝损伤发病机制的研究进展[J]. 药学实践与服务, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
引用本文: 王玉鹏, 鲍婕. 异烟肼致肝损伤发病机制的研究进展[J]. 药学实践与服务, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
WANG Yupeng, BAO Jie. Research progress on the pathogenesis of isoniazid induced liver injury[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
Citation: WANG Yupeng, BAO Jie. Research progress on the pathogenesis of isoniazid induced liver injury[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(4): 289-293. doi: 10.3969/j.issn.1006-0111.2019.04.001
参考文献 (54)

目录

    /

    返回文章
    返回