{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:31:07Z","timestamp":1790897467689,"version":"4.1.0"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["117459"],"award-info":[{"award-number":["117459"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Letters"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1016\/j.toxlet.2020.01.018","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T02:26:54Z","timestamp":1579660014000},"page":"104-110","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":53,"special_numbering":"C","title":["Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin"],"prefix":"10.1016","volume":"322","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-9097","authenticated-orcid":false,"given":"Monique","family":"Combrink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du Toit","family":"Loots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"du Preez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxlet.2020.01.018_bib0005","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.rmed.2009.07.010","article-title":"Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis","volume":"103","author":"Ahmad","year":"2009","journal-title":"Respir. Med."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0010","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/jat.1591","article-title":"GC\u2013MS-based metabolomics reveals mechanism of action for hydrazine induced hepatotoxicity in rats","volume":"31","author":"Bando","year":"2011","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0015","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/jgh.12516","article-title":"Mechanisms of isoniazid\u2010induced idiosyncratic liver injury: emerging role of mitochondrial stress","volume":"29","author":"Boelsterli","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0020","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.taap.2004.06.031","article-title":"Comparative metabonomics of differential hydrazine toxicity in the rat and mouse","volume":"204","author":"Bollard","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0025","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.bbrc.2018.02.030","article-title":"First-line anti-tuberculosis drugs induce hepatotoxicity: a novel mechanism based on a urinary metabolomics platform","volume":"497","author":"Cao","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0030","doi-asserted-by":"crossref","first-page":"4630","DOI":"10.1021\/pr300430u","article-title":"Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response","volume":"11","author":"Cunningham","year":"2012","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0035","doi-asserted-by":"crossref","first-page":"306","DOI":"10.2174\/2213235X113016660006","article-title":"Using metabolomics for elucidating the mechanisms related to tuberculosis treatment failure","volume":"1","author":"De Villiers","year":"2013","journal-title":"Curr. Metabolomics"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0040","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1080\/03602532.2018.1559184","article-title":"Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance","volume":"50","author":"Du Preez","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0045","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2217\/bmm-2016-0287","article-title":"Metabolomics biomarkers for tuberculosis diagnostics: current status and future objectives","volume":"11","author":"Du Preez","year":"2017","journal-title":"Biomarkers"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0050","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.tube.2019.03.003","article-title":"The application of metabolomics toward pulmonary tuberculosis research","volume":"115","author":"Du Preez","year":"2019","journal-title":"Tuberculosis"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0055","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.trac.2004.11.021","article-title":"Metabolomics: current analytical platforms and methodologies","volume":"24","author":"Dunn","year":"2005","journal-title":"Trac Trends Anal. Chem."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0060","doi-asserted-by":"crossref","first-page":"569","DOI":"10.2133\/dmpk.DMPK-11-RG-055","article-title":"Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human urine","volume":"26","author":"Feng","year":"2011","journal-title":"Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0065","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1021\/tx0498915","article-title":"Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity in the rat","volume":"18","author":"Garrod","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0070","first-page":"178","article-title":"Suicidal isoniazid poisoning","volume":"21","author":"Khoharo","year":"2009","journal-title":"J. Ayub Med. Coll. Abbottabad"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0075","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nm.3104","article-title":"Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy","volume":"19","author":"Li","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0080","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1124\/dmd.116.070920","article-title":"A high dose of isoniazid disturbs endobiotic homeostasis in mouse liver","volume":"44","author":"Li","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0085","first-page":"696","article-title":"Metabonomic profile of urine from rats administrated with different treatment period of rifampin","volume":"30","author":"Liao","year":"2008","journal-title":"Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0090","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1600-079X.2004.00176.x","article-title":"Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model","volume":"38","author":"Loots","year":"2005","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0095","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2217\/bmm-2017-0141","article-title":"The role of metabolomics in tuberculosis treatment research","volume":"11","author":"Luies","year":"2017","journal-title":"Biomark. Med."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0100","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.bcp.2011.08.003","article-title":"Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine","volume":"82","author":"Nakajima","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0105","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1021\/tx000231j","article-title":"Metabonomic investigations into hydrazine toxicity in the rat","volume":"14","author":"Nicholls","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0110","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jceh.2012.12.001","article-title":"Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management","volume":"3","author":"Ramappa","year":"2013","journal-title":"J. Clin. Exp. Hepatol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0115","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1177\/0960327117705426","article-title":"Metabolomics approach discriminates toxicity index of pyrazinamide and its metabolic products, pyrazinoic acid and 5-hydroxy pyrazinoic acid","volume":"37","author":"Rawat","year":"2018","journal-title":"Hum. Exp. Toxicol."},{"issue":"Suppl. 1","key":"10.1016\/j.toxlet.2020.01.018_bib0120","doi-asserted-by":"crossref","first-page":"S146","DOI":"10.1093\/toxsci\/kfq358","article-title":"Metabolomics in toxicology: preclinical and clinical applications","volume":"120","author":"Robertson","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0125","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clinbiochem.2010.08.016","article-title":"Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: a review","volume":"44","author":"Roux","year":"2011","journal-title":"Clin. Biochem."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0130","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.toxlet.2018.05.032","article-title":"Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by 1H NMR based metabolomics approach","volume":"295","author":"Ruan","year":"2018","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0135","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1021\/acs.chemrestox.6b00121","article-title":"Chronic treatment with isoniazid causes protoporphyrin IX accumulation in mouse liver","volume":"29","author":"Sachar","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0140","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2174\/1389200216666150812123725","article-title":"Adverse drug reactions to anti-TB Drugs: pharmacogenomics perspective for identification of host genetic markers","volume":"16","author":"Sahu","year":"2015","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0145","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/BF01970674","article-title":"Proton NMR spectroscopic studies on the metabolism and biochemical effects of hydrazine in vivo","volume":"66","author":"Sanins","year":"1992","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0150","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1164\/rccm.200510-1666ST","article-title":"An official ATS statement: hepatotoxicity of antituberculosis therapy","volume":"174","author":"Saukkonen","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0155","first-page":"111","article-title":"Rifampicin adverse effects","volume":"9","author":"Tripathi","year":"1991","journal-title":"Lung India"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0160","series-title":"Global Tuberculosis Report 2019 World Health Organization","first-page":"284","author":"WHO","year":"2019"},{"key":"10.1016\/j.toxlet.2020.01.018_bib0165","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1146\/annurev.pharmtox.45.120403.100120","article-title":"The magic bullets and tuberculosis drug targets","volume":"45","author":"Zhang","year":"2004","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.toxlet.2020.01.018_bib0170","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1039\/C6TX00245E","article-title":"Pyrazinamide-induced hepatotoxicity and gender differences in rats as revealed by a (1)H NMR based metabolomics approach","volume":"6","author":"Zhao","year":"2017","journal-title":"Toxicol. Res."}],"container-title":["Toxicology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427420300266?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427420300266?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:53:27Z","timestamp":1777568007000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378427420300266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":34,"alternative-id":["S0378427420300266"],"URL":"https:\/\/doi.org\/10.1016\/j.toxlet.2020.01.018","relation":{},"ISSN":["0378-4274"],"issn-type":[{"value":"0378-4274","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin","name":"articletitle","label":"Article Title"},{"value":"Toxicology Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxlet.2020.01.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}