PMID- 25858767
OWN - NLM
STAT- MEDLINE
DCOM- 20160229
LR  - 20150604
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 29
IP  - 5
DP  - 2015 Aug
TI  - Acute toxicity of CCl4 but not of paracetamol induces a transcriptomic signature 
      of fibrosis in precision-cut liver slices.
PG  - 1012-20
LID - S0887-2333(15)00056-9 [pii]
LID - 10.1016/j.tiv.2015.03.015 [doi]
AB  - In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce 
      liver necrosis, but long-term treatment with CCl4, in contrast to paracetamol, 
      causes liver fibrosis. The aim of this study was to perform transcriptomic 
      analysis to compare the early changes in mRNA expression profiles induced by APAP 
      and CCl4 in the rat precision-cut liver slice model (PCLS) and to identify early 
      markers that could predict fibrosis-inducing potential. Microarray data of rat 
      PCLS exposed to APAP andCCl4was generated using a toxic dose based on decrease in 
      ATP levels. Toxicity pathway analysis using a custom made fibrosis-related gene 
      list showed fibrosis as one of the predominant toxic endpoints in CCl4-treated, 
      but not in APAP-treated PCLS. Moreover, genes which have a role in fibrosis such 
      as alpha-B crystallin, jun proto-oncogene, mitogen-activated protein kinase 6, 
      serpin peptidase inhibitor and also the transcription factor 
      Kruppel-like-factor-6 were up-regulated by CCl4, but not by APAP. Predicted 
      activation or inhibition of several upstream regulators due to CCl4 is in 
      accordance with their role in fibrosis. In conclusion, transcriptomic analysis of 
      PCLS successfully identified the fibrotic potential of CCl4 as opposed to APAP. 
      The application of PCLS as an ex vivo model to identify early biomarkers to 
      predict the fibrogenic potential of toxic compounds should be further explored.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Vatakuti, Suresh
AU  - Vatakuti S
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, 
      Groningen Research Institute for Pharmacy, University of Groningen, Groningen, 
      The Netherlands.
FAU - Schoonen, Willem G E J
AU  - Schoonen WG
AD  - Toxicology Consultant, Oss, The Netherlands.
FAU - Elferink, Marieke L G
AU  - Elferink ML
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, 
      Groningen Research Institute for Pharmacy, University of Groningen, Groningen, 
      The Netherlands.
FAU - Groothuis, Geny M M
AU  - Groothuis GM
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, 
      Groningen Research Institute for Pharmacy, University of Groningen, Groningen, 
      The Netherlands.
FAU - Olinga, Peter
AU  - Olinga P
AD  - Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, 
      Groningen Research Institute for Pharmacy, University of Groningen, Groningen, 
      The Netherlands. Electronic address: p.olinga@rug.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150406
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (RNA, Messenger)
RN  - 362O9ITL9D (Acetaminophen)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Acetaminophen/*toxicity
MH  - Animals
MH  - Carbon Tetrachloride/*toxicity
MH  - Gene Expression Profiling
MH  - Liver/*drug effects/metabolism
MH  - Liver Cirrhosis/*genetics
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/metabolism
MH  - Rats, Wistar
OTO - NOTNLM
OT  - CCl(4)
OT  - Paracetamol
OT  - Precision cut liver slices
OT  - Prediction of fibrosis
EDAT- 2015/04/11 06:00
MHDA- 2016/03/02 06:00
CRDT- 2015/04/11 06:00
PHST- 2014/11/26 00:00 [received]
PHST- 2015/03/10 00:00 [revised]
PHST- 2015/03/18 00:00 [accepted]
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
AID - S0887-2333(15)00056-9 [pii]
AID - 10.1016/j.tiv.2015.03.015 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2015 Aug;29(5):1012-20. doi: 10.1016/j.tiv.2015.03.015. Epub 
      2015 Apr 6.