First-line anti-tuberculosis drugs induce hepatotoxicity: A novel mechanism based on a urinary metabolomics platform
| Autor: | Yicong Bian, Liyan Miao, Cuilin Shi, Linsheng Liu, Yijun Mi, Chenrong Huang, Jun Cao, Zhijian Ye |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Purine Tuberculosis Antitubercular Agents Biophysics Pharmacology Biochemistry Mass Spectrometry Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Isoniazid Humans Metabolomics Medicine Molecular Biology Chromatography High Pressure Liquid Ethambutol Hypoxanthine business.industry Cell Biology Middle Aged Pyrazinamide medicine.disease Regimen 030104 developmental biology Liver chemistry Purines 030220 oncology & carcinogenesis Female Chemical and Drug Induced Liver Injury Rifampin business Metabolic Networks and Pathways Rifampicin medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 497:485-491 |
| ISSN: | 0006-291X |
| Popis: | Tuberculosis (TB) has become a global public health and social threat. As clinical first-line drugs, rifampicin and isoniazid used in combination with pyrazinamide and ethambutol (the HRZE regimen) usually induce hepatotoxicity. However, the mechanisms underlying this phenomenon remain unclear, and studying the metabolic impact of co-treating TB patients with the HRZE regimen can provide new hepatotoxicity evidence. In this study, urine metabolites from TB patients were profiled using a high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) platform. The tricarboxylic acid circulation, arginine and proline metabolism and purine metabolic pathways were found to be affected by anti-TB drugs. The levels of pyroglutamate, isocitrate, citrate, and xanthine were significantly decreased after the administration of HRZE. The above mentioned pathways were also different between drug-induced liver injury (DILI) and non-DILI patients. Urate and cis-4-octenedioic acid levels in the DILI group were significantly increased compared to those in the non-DILI group, while the cis-aconitate and hypoxanthine levels were significantly decreased. These results highlight that superoxide generation can aggravate the hepatotoxic effects of the HRZE regimen. In addition, our metabolomic approach had the ability to predict hepatotoxicity for clinical applications. |
| Databáze: | OpenAIRE |
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