Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin

•Isoniazid and rifampicin are the most important first-line TB drugs.•Despite the drugs’ anti-mycobacterial properties, it can cause severe side effects.•Drug toxicity is a major contributor to TB treatment failure.•Metabolomics can be used to elucidate TB drug toxicity mechanisms.•Metabolomics can...

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Bibliographic Details
Published in:Toxicology letters 2020-04, Vol.322, p.104-110
Main Authors: Combrink, Monique, Loots, Du Toit, du Preez, Ilse
Format: Article
Language:English
Subjects:
Animals
Antitubercular Agents - metabolism
Antitubercular Agents - toxicity
Biomarkers - metabolism
Biotransformation
Drug-Related Side Effects and Adverse Reactions - diagnosis
Drug-Related Side Effects and Adverse Reactions - etiology
Drug-Related Side Effects and Adverse Reactions - metabolism
Humans
Isoniazid
Isoniazid - metabolism
Isoniazid - toxicity
Metabolomics
Metabolomics - methods
Rifampicin
Rifampin - metabolism
Rifampin - toxicity
Risk Assessment
Toxicity
Toxicity Tests - methods
Tuberculosis
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Summary:•Isoniazid and rifampicin are the most important first-line TB drugs.•Despite the drugs’ anti-mycobacterial properties, it can cause severe side effects.•Drug toxicity is a major contributor to TB treatment failure.•Metabolomics can be used to elucidate TB drug toxicity mechanisms.•Metabolomics can contribute to the development of less toxic TB drugs. Isoniazid and rifampicin are well-known anti-mycobacterial agents and are widely used to treat pulmonary tuberculosis (TB) as part of the combined therapy approach, recommended by the World Health Organization. The ingestion of these first-line TB drugs are, however, not free of side effects, and are toxic to the liver, kidney, and central nervous system. These side effects are associated with poor treatment compliance, resulting in TB treatment failure, relapse and drug resistant TB. This occurrence has subsequently led to the recent application of novel research technologies, towards a better understanding of the underlying toxicity mechanisms of TB drugs in humans, mostly focussing on the 2 most important TB drugs: isoniazid and rifampicin. In this review, we discuss the contribution that one such an approach, termed metabolomics has made toward this field, and also highlight the impact that this might have towards the development of improved TB treatment regimens.
ISSN:0378-4274
1879-3169
DOI:10.1016/j.toxlet.2020.01.018