Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Friday, 07 / 19 / 2019

Articles

Mitochondrial Damage and Drp1 Overexpression in Rifampicin- and Isoniazid-induced Liver Injury Cell Model

ORIGINAL ARTICLE

Mitochondrial Damage and Drp1 Overexpression in Rifampicin- and Isoniazid-induced Liver Injury Cell Model

Fangfang Li#,2, Juan Zhou#,3, Yi Li4, Kewei Sun5 and Jun Chen1,*

1Department of Liver Diseases, Third Hospital of Shenzhen, Shenzhen, Guangdong, China
2Department of Digestive Diseases, First Hospital of Chenzhou, Chenzhou, Hunan, China
3Department of Infectious Diseases, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan, China
4Liver Diseases Center, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
5Department of Infectious Diseases, First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
#These two authors contributed equally to this work.
*Correspondence to: Jun Chen, Department of Liver Diseases, Third Hospital of Shenzhen, Shenzhen, Guangdong 311115, China. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2019;7(1):40-45 DOI: 10.14218/JCTH.2018.00052
Received: September 20, 2018 Accepted: December 29, 2018 Published online: March 15, 2019

Abstract

Background and Aims: Rifampicin (RFP) and isoniazid (INH) are widely used as anti-tuberculosis agents. However, the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP- and INH-related hepatotoxicity have not been established yet. This study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP- and INH-induced hepatocyte injury.

Methods: Cell injury, changes in mitochondrial function, and expression and activation of dynamin related protein 1 (Drp1), known as the main protein for mitochondrial fission, were analyzed in cultured QSG7701 cells exposed to RFP and INH.

Results: INH and RFP treatment induced pronounced hepatocyte injury and increased cell death. In the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease, changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH (p < 0.05). Particularly, we observed the overactivation and mitochondrial translocation of Drp1 in RFP-induced cell injury, which was not occurred with exposure to INH.

Conclusions: RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1-mediated mitochondrial fission.

Keywords

Anti-tuberculosis drug-induced liver injury, Drp1, Mitochondrial dysfunction, Mitochondrial fission

 

 

 

 

Journal of Clinical and Translational Hepatology 2019 vol. 7, 40-45  [ Html ] [ PDF Full-text ]

 

© The Authors 2018. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

 

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