PMID- 20371285
OWN - NLM
STAT- MEDLINE
DCOM- 20100617
LR  - 20181201
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 24
IP  - 4
DP  - 2010 Jun
TI  - Participation of lipid transport and fatty acid metabolism in valproate 
      sodium-induced hepatotoxicity in HepG2 cells.
PG  - 1086-91
LID - 10.1016/j.tiv.2010.03.014 [doi]
AB  - The hepatotoxicity induced by valproic acid (VPA) has been described in many 
      clinical studies and the related mechanism has been partly elucidated. The 
      objective of this study is to investigate the hepatotoxicity and its underlying 
      mechanism of valproic acid on human hepatoma carcinoma cell line HepG2. The cell 
      viability was evaluated by 3-(4,5-dimethyltyiazol-2-yl)-2,5-diphenyltetrazolium 
      bromide (MTT) assay. The activities of alanine aminotransferase (ALT), aspartate 
      aminotransferase (AST) and lactate dehydrogenase (LDH) in the medium were 
      detected using spectrophotometry. The gene expressions of cytochrome P450 1 A1 
      (CYP1A1), ATP-binding cassette transporter G1 (ABCG1) and carnitine 
      palmitoyltransferase 1 (CPT1A), related to lipid transport and fatty acid 
      metabolism, were measured by quantitative real-time reverse transcriptase-PCR. 
      Treatment with valproate sodium obviously decreased the viability of HepG2 cells, 
      accompanied by the increased leakages of ALT, AST and LDH in a dose-dependent 
      manner. Furthermore, the gene expressions of CYP1A1, ABCG1 and CPT1A were almost 
      up-regulated in the treated groups. In conclusion, these data suggest that 
      VPA-induced hepatotoxicity was critically enhanced with the elevation of 
      valproate sodium, which may be correlated with up-regulated gene expressions of 
      CYP1A1, ABCG1 and CPT1A.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
FAU - Ji, Qiaoli
AU  - Ji Q
AD  - Department of Pharmacology and Pharmacy, Key Laboratory of Environment and Genes 
      Related to Diseases, School of Medicine, Xi'an Jiaotong University, Xi'an, 
      Shaanxi 710061, PR China.
FAU - Shi, Xiaolian
AU  - Shi X
FAU - Lin, Rong
AU  - Lin R
FAU - Mao, Youhua
AU  - Mao Y
FAU - Zhai, Xiaogang
AU  - Zhai X
FAU - Lin, Qinqin
AU  - Lin Q
FAU - Zhang, Jiye
AU  - Zhang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100403
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Anticonvulsants)
RN  - 0 (Fatty Acids)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Alanine Transaminase/metabolism
MH  - Anticonvulsants/*toxicity
MH  - Aspartate Aminotransferases/metabolism
MH  - Carnitine O-Palmitoyltransferase/metabolism
MH  - Cell Survival/drug effects
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Fatty Acids/*metabolism
MH  - Gene Expression/drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipid Metabolism/*drug effects
MH  - Liver/*drug effects/metabolism
MH  - Toxicity Tests
MH  - Valproic Acid/*toxicity
EDAT- 2010/04/08 06:00
MHDA- 2010/06/18 06:00
CRDT- 2010/04/08 06:00
PHST- 2009/10/10 00:00 [received]
PHST- 2010/03/08 00:00 [revised]
PHST- 2010/03/25 00:00 [accepted]
PHST- 2010/04/08 06:00 [entrez]
PHST- 2010/04/08 06:00 [pubmed]
PHST- 2010/06/18 06:00 [medline]
AID - S0887-2333(10)00078-0 [pii]
AID - 10.1016/j.tiv.2010.03.014 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2010 Jun;24(4):1086-91. doi: 10.1016/j.tiv.2010.03.014. Epub 
      2010 Apr 3.