PMID- 18375824
OWN - NLM
STAT- MEDLINE
DCOM- 20080530
LR  - 20220311
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Electronic)
IS  - 1535-3699 (Linking)
VI  - 233
IP  - 5
DP  - 2008 May
TI  - Zinc supplementation inhibits hepatic apoptosis in mice subjected to a long-term 
      ethanol exposure.
PG  - 540-8
LID - 10.3181/0710-RM-265 [doi]
AB  - Hepatocyte apoptosis has been documented in both clinical and experimental 
      alcoholic liver disease. This study was undertaken to examine the effect of 
      dietary zinc supplementation on hepatic apoptosis in mice subjected to a 
      long-term ethanol exposure. Male adult 129S6 mice fed an ethanol-containing 
      liquid diet for 6 months developed hepatitis, as indicated by neutrophil 
      infiltration and elevation of hepatic keratinocyte chemoattractant (KC) and 
      monocyte chemoattractant protein-1 (MCP-1) levels. Apoptotic cell death was 
      detected in ethanol-exposed mice by a terminal deoxynucleotidyl transferase dUTP 
      nick end labeling (TUNEL) assay and was confirmed by the increased activities of 
      caspase-3 and -8. Zinc supplementation attenuated alcoholic hepatitis and reduced 
      the number of TUNEL-positive cells in association with inhibition of caspase 
      activities. Ethanol exposure caused oxidative stress, as indicated by reactive 
      oxygen species accumulation, mitochondrial glutathione depletion, and decreased 
      metallothionein levels in the liver, which were suppressed by zinc 
      supplementation. The mRNA levels of tumor necrosis factor (TNF)-alpha, TNF-R1, 
      FasL, Fas, Fas-associated factor-1, and caspase-3 in the liver were upregulated 
      by ethanol exposure, which were attenuated by zinc supplementation. Zinc 
      supplementation also prevented ethanol-elevated serum and hepatic TNF-alpha 
      levels and TNF-R1 and Fas proteins in the liver. In conclusion, zinc 
      supplementation prevented hepatocyte apoptosis in mice subjected to long-term 
      ethanol exposure, and the action of zinc is likely through suppression of 
      oxidative stress and death receptor-mediated pathways.
FAU - Zhou, Zhanxiang
AU  - Zhou Z
AD  - The University of Louisville School of Medicine, Department of Medicine, 511 
      South Floyd Street, MDR Room 529, Louisville, KY 40292, USA. 
      z0zhou01@louisville.edu
FAU - Liu, Jie
AU  - Liu J
FAU - Song, Zhenyuan
AU  - Song Z
FAU - McClain, Craig J
AU  - McClain CJ
FAU - Kang, Y James
AU  - Kang YJ
LA  - eng
GR  - R01 AA014623/AA/NIAAA NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080328
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 3K9958V90M (Ethanol)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animal Feed
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Body Weight/drug effects
MH  - Ethanol/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Liver Diseases, Alcoholic/metabolism/*pathology/*prevention & control
MH  - Male
MH  - Mice
MH  - Organ Size/drug effects
MH  - Oxidative Stress/drug effects
MH  - Time Factors
MH  - Zinc/*pharmacology
PMC - PMC5895093
MID - NIHMS955233
EDAT- 2008/04/01 09:00
MHDA- 2008/05/31 09:00
PMCR- 2018/04/11
CRDT- 2008/04/01 09:00
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/05/31 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
PHST- 2018/04/11 00:00 [pmc-release]
AID - 0710-RM-265 [pii]
AID - 10.3181/0710-RM-265 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2008 May;233(5):540-8. doi: 10.3181/0710-RM-265. Epub 
      2008 Mar 28.