PMID- 20595623
OWN - NLM
STAT- MEDLINE
DCOM- 20100924
LR  - 20211020
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 299
IP  - 3
DP  - 2010 Sep
TI  - Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis.
PG  - G661-8
LID - 10.1152/ajpgi.00287.2009 [doi]
AB  - Ethanol metabolism in the liver induces oxidative stress and altered cytokine 
      production preceding myofibroblast activation and fibrogenic responses. The 
      purpose of this study was to determine how ethanol affects the fibrogenic 
      response in precision-cut liver slices (PCLS). PCLS were obtained from chow-fed 
      male Wistar rats (200-300 g) and were cultured up to 96 h in medium, 25 mM 
      ethanol, or 25 mM ethanol and 0.5 mM 4-methylpyrazole (4-MP), an inhibitor of 
      ethanol metabolism. Slices from every time point (24, 48, 72, and 96 h) were 
      examined for glutathione (GSH) levels, lipid peroxidation [thiobarbituric 
      acid-reactive substance (TBARS) assay], cytokine production (ELISA and RT-PCR), 
      and myofibroblast activation [immunoblotting and immunohistochemistry for smooth 
      muscle actin (SMA) and collagen]. Treatment of PCLS with 25 mM ethanol induced 
      significant oxidative stress within 24 h, including depletion of cellular GSH and 
      increased lipid peroxidation compared with controls (P < 0.05). Ethanol treatment 
      also elicited a significant and sustained increase in interleukin-6 (IL-6) 
      production (P < 0.05). Importantly, ethanol treatment accelerates a fibrogenic 
      response after 48 h, represented by significant increases in SMA and collagen 
      1alpha(I) production (P < 0.05). These ethanol-induced effects were prevented by 
      the addition of 4-MP. Ethanol metabolism induces oxidative stress (GSH depletion 
      and increased lipid peroxidation) and sustained IL-6 expression in rat PCLS. 
      These phenomena precede and coincide with myofibroblast activation, which occurs 
      within 48 h of treatment. These results indicate the PCLS can be used as in vitro 
      model for studying multicellular interactions during the early stages of 
      ethanol-induced liver injury and fibrogenesis.
FAU - Schaffert, Courtney S
AU  - Schaffert CS
AD  - Veterans Affairs Medical Center and the Department of Internal Medicine, 
      University of Nebraska Medical Center, Omaha, USA.
FAU - Duryee, Michael J
AU  - Duryee MJ
FAU - Bennett, Robert G
AU  - Bennett RG
FAU - DeVeney, Amy L
AU  - DeVeney AL
FAU - Tuma, Dean J
AU  - Tuma DJ
FAU - Olinga, Peter
AU  - Olinga P
FAU - Easterling, Karen C
AU  - Easterling KC
FAU - Thiele, Geoffrey M
AU  - Thiele GM
FAU - Klassen, Lynell W
AU  - Klassen LW
LA  - eng
GR  - R01 AA10435/AA/NIAAA NIH HHS/United States
GR  - R21 AA15505-01A2/AA/NIAAA NIH HHS/United States
GR  - R37 AA07818/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100701
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Interleukin-6)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Ethanol/*toxicity
MH  - Fibroblasts/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Interleukin-6/genetics/metabolism
MH  - Lipid Peroxidation
MH  - Liver/cytology/*drug effects
MH  - Liver Cirrhosis/*chemically induced/pathology
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
PMC - PMC2950678
EDAT- 2010/07/03 06:00
MHDA- 2010/09/25 06:00
PMCR- 2011/09/01
CRDT- 2010/07/03 06:00
PHST- 2010/07/03 06:00 [entrez]
PHST- 2010/07/03 06:00 [pubmed]
PHST- 2010/09/25 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - ajpgi.00287.2009 [pii]
AID - GI-00287-2009 [pii]
AID - 10.1152/ajpgi.00287.2009 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G661-8. doi: 
      10.1152/ajpgi.00287.2009. Epub 2010 Jul 1.