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Article

An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage

by 1, 1,2 and 1,2,*
1
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore
2
NUS Graduate School for Integrative Sciences & Engineering, Centre for Life Sciences, National University of Singapore, Singapore 119077, Singapore
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3714; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103714
Received: 10 April 2020 / Revised: 19 May 2020 / Accepted: 22 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Molecular Mechanisms and Biomarkers in Drug-Induced Organ Injury)
Tuberculosis remains a significant infectious lung disease that affects millions of patients worldwide. Despite numerous existing drug regimens for tuberculosis, drug-induced liver injury is a major challenge that limits the effectiveness of these therapeutics. Two drugs that form the backbone of the commonly administered quadruple antitubercular regimen, that is, pyrazinamide (PZA) and isoniazid (INH), are associated with such hepatotoxicity. Yet, we lack safe and effective alternatives to the antitubercular regimen. Consequently, current research largely focuses on exploiting the hepatoprotective effect of nutraceutical compounds as complementary therapy. Silibinin, a herbal product widely believed to protect against various liver diseases, potentially provides a useful solution given its hepatoprotective mechanisms. In our study, we identified silibinin’s role in mitigating PZA- and INH-induced hepatotoxicity and elucidated a deeper mechanistic understanding of silibinin’s hepatoprotective ability. Silibinin preserved the viability of human foetal hepatocyte line LO2 when co-administered with 80 mM INH and decreased apoptosis induced by a combination of 40 mM INH and 10 mM PZA by reducing oxidative damage to mitochondria, proteins, and lipids. Taken together, this proof-of-concept forms the rational basis for the further investigation of silibinin’s hepatoprotective effect in subsequent preclinical studies and clinical trials. View Full-Text
Keywords: drug-induced liver injury (DILI); silibinin; oxidative stress; tuberculosis; pyrazinamide; isoniazid drug-induced liver injury (DILI); silibinin; oxidative stress; tuberculosis; pyrazinamide; isoniazid
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MDPI and ACS Style

Goh, Z.-H.; Tee, J.K.; Ho, H.K. An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage. Int. J. Mol. Sci. 2020, 21, 3714. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103714

AMA Style

Goh Z-H, Tee JK, Ho HK. An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage. International Journal of Molecular Sciences. 2020; 21(10):3714. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103714

Chicago/Turabian Style

Goh, Zhang-He, Jie K. Tee, and Han K. Ho 2020. "An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage" International Journal of Molecular Sciences 21, no. 10: 3714. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103714

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