PMID- 21419764
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20161125
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 659
IP  - 1
DP  - 2011 May 20
TI  - The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin 
      induced liver injury in mice.
PG  - 53-60
LID - 10.1016/j.ejphar.2011.03.007 [doi]
AB  - Antitubercular drugs have been known to be potentially hepatotoxic and may lead 
      to drug-induced liver injury. In this study, we aimed to investigate the 
      protective effects of ursodeoxycholic acid (UDCA) on liver injury caused by 
      co-administration with isoniazid and rifampicin, two famous antitubercular drugs. 
      Liver injury was induced by co-treatment with isoniazid (75mg/kg) and rifampicin 
      (150mg/kg) for one week. Mice were orally administered with UDCA (15, 50 and 
      150mg/kg) 30min before isoniazid and rifampicin. We show that serum alanine 
      aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly 
      increased in mice treated with isoniazid plus rifampicin. An obvious fatty 
      accumulation, accompanied by mild necrosis and inflammation, was observed in 
      liver of mice treated with rifampicin plus isoniazid. In addition, isoniazid plus 
      rifampicin resulted in hepatic apoptosis, as determined by terminal dUTP nick-end 
      labeling (TUNEL) staining and caspase-3 activation. Additional experiment showed 
      that isoniazid plus rifampicin significantly increased the level of hepatic 
      malondialdehyde (MDA) and caused glutathione (GSH) depletion and 3-nitrotyrosine 
      (3-NT) residues in liver. UDCA pretreatment significantly attenuated isoniazid 
      plus rifampicin induced oxidative stress in liver. Importantly, UDCA pretreatment 
      significantly alleviated isoniazid plus rifampicin induced hepatic apoptosis. 
      Moreover, UDCA-mediated anti-apoptotic effect seemed to be associated with its 
      regulation of Bcl-2 and Bax gene expression in liver. These findings suggest that 
      UDCA might protect against isoniazid and rifampicin induced liver injury through 
      its anti-oxidative and anti-apoptotic effects.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Chen, Xi
AU  - Chen X
AD  - Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei 230022, China.
FAU - Xu, Juan
AU  - Xu J
AD  - Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei 230022, China.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Yu, Tao
AU  - Yu T
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Zhao, Mei
AU  - Zhao M
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Duan, Zi-Hao
AU  - Duan ZH
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Xu, Jian-Ming
AU  - Xu JM
AD  - Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei 230022, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110322
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antioxidants)
RN  - 0 (Antitubercular Agents)
RN  - 724L30Y2QR (Ursodeoxycholic Acid)
RN  - V83O1VOZ8L (Isoniazid)
RN  - VJT6J7R4TR (Rifampin)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Antitubercular Agents/*adverse effects
MH  - Apoptosis/drug effects
MH  - Chemical and Drug Induced Liver Injury/metabolism/pathology/*prevention & control
MH  - Cytoprotection/*drug effects
MH  - Drug Interactions
MH  - Female
MH  - Isoniazid/*adverse effects
MH  - Liver/drug effects/metabolism/pathology
MH  - Mice
MH  - Oxidative Stress/drug effects
MH  - Rifampin/*adverse effects
MH  - Ursodeoxycholic Acid/*pharmacology
EDAT- 2011/03/23 06:00
MHDA- 2016/06/28 06:00
CRDT- 2011/03/23 06:00
PHST- 2010/11/17 00:00 [received]
PHST- 2011/03/01 00:00 [revised]
PHST- 2011/03/08 00:00 [accepted]
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
AID - S0014-2999(11)00262-7 [pii]
AID - 10.1016/j.ejphar.2011.03.007 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2011 May 20;659(1):53-60. doi: 10.1016/j.ejphar.2011.03.007. 
      Epub 2011 Mar 22.