PMID- 12937155
OWN - NLM
STAT- MEDLINE
DCOM- 20030922
LR  - 20211103
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 163
IP  - 3
DP  - 2003 Sep
TI  - A critical involvement of oxidative stress in acute alcohol-induced hepatic 
      TNF-alpha production.
PG  - 1137-46
AB  - Tumor necrosis factor-alpha (TNF-alpha) production is a critical factor in the 
      pathogenesis of alcoholic liver injury. Both oxidative stress and endotoxin have 
      been implicated in the process of alcohol-induced TNF-alpha production. However, 
      a cause-and-effect relationship between these factors has not been fully defined. 
      The present study was undertaken to determine the mediators of acute 
      alcohol-induced TNF-alpha production using a mouse model of acute alcohol 
      hepatotoxicity. Alcohol administration via gavage at a dose of 6 g/kg to 129/Sv 
      mice induced hepatic TNF-alpha production in Kupffer cells as demonstrated by 
      measuring protein levels, immunohistochemical localization, and mRNA expression. 
      Alcohol intoxication caused liver injury in association with increases in plasma 
      endotoxin and hepatic lipid peroxidation. Treatment with an endotoxin 
      neutralizing protein significantly suppressed alcohol-induced elevation of plasma 
      endotoxin, hepatic lipid peroxidation, and inhibited TNF-alpha production. 
      Treatment with antioxidants, N-ACETYL-L-CYSTEINE, or dimethylsulfoxide, failed to 
      attenuate plasma endotoxin elevation, but significantly inhibited alcohol-induced 
      hepatic lipid peroxidation, TNF-alpha production and steatosis. All treatments 
      prevented alcohol-induced necrotic cell death in the liver. This study thus 
      systemically dissected the relationship among plasma endotoxin elevation, hepatic 
      oxidative stress, and TNF-alpha production following acute alcohol 
      administration, and the results demonstrate that oxidative stress mediates 
      endotoxin-induced hepatic TNF-alpha production in acute alcohol intoxication.
FAU - Zhou, Zhanxiang
AU  - Zhou Z
AD  - Department of Medicine, University of Louisville School of Medicine, 511 South 
      Floyd Street, MDR 525, Louisville, KY, USA. z0zhou01@louisville.edu
FAU - Wang, Lipeng
AU  - Wang L
FAU - Song, Zhenyuan
AU  - Song Z
FAU - Lambert, Jason C
AU  - Lambert JC
FAU - McClain, Craig J
AU  - McClain CJ
FAU - Kang, Y James
AU  - Kang YJ
LA  - eng
GR  - HL 63760/HL/NHLBI NIH HHS/United States
GR  - R01 HL063760/HL/NHLBI NIH HHS/United States
GR  - R01 HL059225/HL/NHLBI NIH HHS/United States
GR  - HL 59225/HL/NHLBI NIH HHS/United States
GR  - R21 AA013601/AA/NIAAA NIH HHS/United States
GR  - AA 10496/AA/NIAAA NIH HHS/United States
GR  - AA 13601/AA/NIAAA NIH HHS/United States
GR  - AA 01762/AA/NIAAA NIH HHS/United States
GR  - R01 AA010496/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Endotoxins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Endotoxins/blood/metabolism
MH  - Ethanol/*poisoning
MH  - Liver/*drug effects/*metabolism/pathology
MH  - Mice
MH  - *Oxidative Stress
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
PMC - PMC1868249
EDAT- 2003/08/26 05:00
MHDA- 2003/09/23 05:00
PMCR- 2004/03/01
CRDT- 2003/08/26 05:00
PHST- 2003/08/26 05:00 [pubmed]
PHST- 2003/09/23 05:00 [medline]
PHST- 2003/08/26 05:00 [entrez]
PHST- 2004/03/01 00:00 [pmc-release]
AID - S0002-9440(10)63473-6 [pii]
AID - 3751 [pii]
AID - 10.1016/s0002-9440(10)63473-6 [doi]
PST - ppublish
SO  - Am J Pathol. 2003 Sep;163(3):1137-46. doi: 10.1016/s0002-9440(10)63473-6.