PMID- 29976085
OWN - NLM
STAT- MEDLINE
DCOM- 20181022
LR  - 20181022
IS  - 1793-6853 (Electronic)
IS  - 0192-415X (Linking)
VI  - 46
IP  - 5
DP  - 2018
TI  - Kaempferol's Protective Effect on Ethanol-Induced Mouse Primary Hepatocytes 
      Injury Involved in the Synchronous Inhibition of SP1, Hsp70 and CYP2E1.
PG  - 1093-1110
LID - 10.1142/S0192415X1850057X [doi]
AB  - The mechanism of ethanol-induced hepatotoxicity was complicated, accompanied by 
      the over-expressions of the cytochrome P450 2E1 (CYP2E1), heat shock protein 70 
      (Hsp70) and the nuclear factor specificity protein 1 (SP1). Kaempferol (Kaem) 
      could protect the ethanol-induced hepatotoxicity likely by inhibiting the CYP2E1 
      expression and activity. This study investigated the protective mechanism(s) of 
      kaempferol on ethanol-induced toxicity by dynamic alteration of SP1, Hsp70 and 
      CYP2E1 among the nucleus and different organelles in hepatocytes. After ethanol 
      treatment alone and co-incubation hepatocytes with kaempferol, protein levels of 
      CYP2E1, Hsp70, and SP1 were determined in vitro (western blotting and 
      immunofluorescence). Hepatocytes' viability was assessed by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods. 
      Glutathione (GSH) levels were evaluated for ethanol-induced oxidative stress. In 
      the ethanol-treated hepatocytes, kaempferol decreased protein levels of CYP2E1 in 
      both microsome and mitochondria, cytosolic Hsp70 and SP1 in nuclear and cytosol, 
      and the oxidative stress and increased the cell viability compared to those of 
      ethanol group. Collectively, our findings propose that the protective mechanism 
      of kaempferol is involved in the synchronous, early and persistent inhibitions of 
      mitochondrial and microsomal CYP2E1, cytosolic Hsp70 and nuclear and cytosolic 
      SP1 in mouse primary hepatocytes' injury induced by ethanol.
FAU - Zhou, Bo
AU  - Zhou B
AD  - * College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 
      712100, P. R. China.
FAU - Jiang, Zhihui
AU  - Jiang Z
AD  - dagger Research Center of Modern Biotechnology, School of Biotechnology and Food 
      Engineering, Anyang Institute of Technology, Anyang, Henan 455000, P. R. China.
FAU - Li, Xinping
AU  - Li X
AD  - * College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 
      712100, P. R. China.
FAU - Zhang, Xiaoying
AU  - Zhang X
AD  - * College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 
      712100, P. R. China.
AD  - dagger Research Center of Modern Biotechnology, School of Biotechnology and Food 
      Engineering, Anyang Institute of Technology, Anyang, Henan 455000, P. R. China.
AD  - double dagger Centre of Molecular and Environmental Biology, Department of Biology, 
      University of Minho, Campus de Gualtar, Braga, Portugal.
LA  - eng
PT  - Journal Article
DEP - 20180705
PL  - Singapore
TA  - Am J Chin Med
JT  - The American journal of Chinese medicine
JID - 7901431
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Kaempferols)
RN  - 0 (Protective Agents)
RN  - 0 (Sp1 Transcription Factor)
RN  - 3K9958V90M (Ethanol)
RN  - 731P2LE49E (kaempferol)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP2E1/genetics/*metabolism
MH  - Ethanol/*adverse effects
MH  - Glutathione/metabolism
MH  - HSP70 Heat-Shock Proteins/genetics/*metabolism
MH  - Hepatocytes/*drug effects/metabolism
MH  - Humans
MH  - Kaempferols/*pharmacology
MH  - Liver/*drug effects/injuries/metabolism
MH  - Liver Diseases, Alcoholic/genetics/*metabolism/prevention & control
MH  - Male
MH  - Mice
MH  - Oxidative Stress/drug effects
MH  - Protective Agents/*pharmacology
MH  - Sp1 Transcription Factor/genetics/*metabolism
OTO - NOTNLM
OT  - Cytochrome P450 2E1 (CYP2E1)
OT  - Ethanol-Induced Hepatotoxicity
OT  - Heat Shock Protein 70 (Hsp70)
OT  - Kaempferol's Hepatoprotection
OT  - Mouse Primary Hepatocytes
OT  - Specificity Protein 1 (SP1)
EDAT- 2018/07/07 06:00
MHDA- 2018/10/23 06:00
CRDT- 2018/07/07 06:00
PHST- 2018/07/07 06:00 [pubmed]
PHST- 2018/10/23 06:00 [medline]
PHST- 2018/07/07 06:00 [entrez]
AID - 10.1142/S0192415X1850057X [doi]
PST - ppublish
SO  - Am J Chin Med. 2018;46(5):1093-1110. doi: 10.1142/S0192415X1850057X. Epub 2018 
      Jul 5.