Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin

• 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
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2020.01.018

•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.