PMID- 31168027
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20190708
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 44
IP  - 6
DP  - 2019
TI  - Ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver 
      injury in rats by suppressing inflammation and oxidative stress.
PG  - 405-414
LID - 10.2131/jts.44.405 [doi]
AB  - Several studies have demonstrated the chemopreventive role of ketoconazole in 
      animal models of liver injury. However, the underlying molecular mechanisms of 
      this hepatoprotective effect are poorly understood. The present study assessed 
      the potential of ketoconazole to enhance resistance to carbon 
      tetrachloride-induced hepatotoxicity in vivo in a rat model. Ketoconazole 
      pretreatment adult male rats were intraperitoneally injected with carbon 
      tetrachloride for 24 hr and various hepatic parameters were analyzed. We observed 
      decreased serum transaminases activity, reduced nuclear RelA/p65 expression, and 
      suppressed production of pro-inflammatory cytokines in the liver tissue. 
      Histopathological examination demonstrated ketoconazole pretreatment to 
      extensively prevent liver injury. In addition, it significantly increased nuclear 
      factor-erythroid 2 p45-related factor 2 (Nrf2) protein expression, glutathione 
      (GSH) to oxidized glutathione (GSSG) ratio, and antioxidant enzymes gene 
      expression. These results suggest that ketoconazole pretreatment ameliorates 
      carbon tetrachloride-induced acute liver injury in rats, signifying its 
      anti-inflammatory and antioxidant functions.
FAU - Zhou, Yunsong
AU  - Zhou Y
AD  - The First Clinical Medical College, Guangzhou Univ Chinese Med, China.
AD  - Lingnan Medical Research Center, Guangzhou Univ Chinese Med, China.
FAU - Peng, Chong
AU  - Peng C
AD  - The First Clinical Medical College, Guangzhou Univ Chinese Med, China.
AD  - Lingnan Medical Research Center, Guangzhou Univ Chinese Med, China.
FAU - Zhou, Zunming
AU  - Zhou Z
AD  - The First Clinical Medical College, Guangzhou Univ Chinese Med, China.
AD  - Lingnan Medical Research Center, Guangzhou Univ Chinese Med, China.
FAU - Huang, Keer
AU  - Huang K
AD  - The First Clinical Medical College, Guangzhou Univ Chinese Med, China.
AD  - The First Affliated Hospital of Guangzhou Univ Chinese Med, China.
AD  - Lingnan Medical Research Center, Guangzhou Univ Chinese Med, China.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - GAN16C9B8O (Glutathione)
RN  - R9400W927I (Ketoconazole)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Carbon Tetrachloride
MH  - Chemical and Drug Induced Liver Injury/*drug therapy/metabolism/pathology
MH  - Cytokines/metabolism
MH  - Glutathione/metabolism
MH  - Ketoconazole/pharmacology/*therapeutic use
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/drug effects
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Acute liver injury
OT  - Adaptive response
OT  - Aryl hydrocarbon receptor
OT  - Carbon tetrachloride
OT  - Ketoconazole
OT  - Nuclear factor erythroid 2-related factor 2
EDAT- 2019/06/07 06:00
MHDA- 2019/07/10 06:00
CRDT- 2019/06/07 06:00
PHST- 2019/06/07 06:00 [entrez]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
AID - 10.2131/jts.44.405 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2019;44(6):405-414. doi: 10.2131/jts.44.405.