机构：[1]Department of Liver Diseases, Third Hospital of Shenzhen, Shenzhen, Guangdong, China深圳市康宁医院深圳医学信息中心[2]Department of Digestive Diseases, First Hospital of Chenzhou, Chenzhou, Hunan, China[3]Department of Infectious Diseases, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan, China[4]Liver Diseases Center, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China[5]Department of Infectious Diseases, First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
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.
基金：
This study was supported by the TCM basis Building Program
of State Administration of Traditional Medicine of the People’s
Republic of China (No. JDZX2015189) and Sanming Project of Medicine in Shenzhen (SZSM201612014).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
无
最新[2025]版：
大类|3 区医学
小类|3 区胃肠肝病学
第一作者：
第一作者机构：[2]Department of Digestive Diseases, First Hospital of Chenzhou, Chenzhou, Hunan, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Liver Diseases, Third Hospital of Shenzhen, Shenzhen, Guangdong, China[*1]Department of Liver Diseases, Third Hospital of Shenzhen, Shenzhen, Guangdong 311115, China.
推荐引用方式(GB/T 7714)：
Li Fangfang,Zhou Juan,Li Yi,et al.Mitochondrial Damage and Drp1 Overexpression in Rifampicin- and Isoniazid-induced Liver Injury Cell Model.[J].Journal of clinical and translational hepatology.2019,7(1):40-45.doi:10.14218/JCTH.2018.00052.
APA：
Li Fangfang,Zhou Juan,Li Yi,Sun Kewei&Chen Jun.(2019).Mitochondrial Damage and Drp1 Overexpression in Rifampicin- and Isoniazid-induced Liver Injury Cell Model..Journal of clinical and translational hepatology,7,(1)
MLA：
Li Fangfang,et al."Mitochondrial Damage and Drp1 Overexpression in Rifampicin- and Isoniazid-induced Liver Injury Cell Model.".Journal of clinical and translational hepatology 7..1(2019):40-45
