PMID- 18599023
OWN - NLM
STAT- MEDLINE
DCOM- 20080804
LR  - 20211020
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 76
IP  - 3
DP  - 2008 Aug 1
TI  - An in vitro method of alcoholic liver injury using precision-cut liver slices 
      from rats.
PG  - 426-36
LID - 10.1016/j.bcp.2008.05.012 [doi]
AB  - Alcohol abuse results in liver injury, but investigations into the mechanism(s) 
      for this injury have been hampered by the lack of appropriate in vitro culture 
      models in which to conduct in depth and specific studies. In order to overcome 
      these shortcomings, we have developed the use of precision-cut liver slices 
      (PCLS) as an in vitro culture model in which to investigate how ethanol causes 
      alcohol-induced liver injury. In these studies, it was shown that the PCLS 
      retained excellent viability as determined by lactate dehydrogenase and adenosine 
      triphosphate (ATP) levels over a 96-h period of incubation. More importantly, the 
      major enzymes of ethanol detoxification; alcohol dehydrogenase, aldehyde 
      dehydrogenase, and cytochrome P4502E1, remained active and PCLS readily 
      metabolized ethanol and produced acetaldehyde. Within 24 h and continuing up to 
      96h the PCLS developed fatty livers and demonstrated an increase in the redox 
      state. These PCLS secreted albumin, and albumin secretion was decreased by 
      ethanol treatment. All of these impairments were reversed following the addition 
      of 4-methylpyrazole, which is an inhibitor of ethanol metabolism. Therefore, this 
      model system appears to mimic the ethanol-induced changes in the liver that have 
      been previously reported in human and animal studies, and may be a useful model 
      for the study of alcoholic liver disease.
FAU - Klassen, Lynell W
AU  - Klassen LW
AD  - Experimental Immunology Laboratory, University of Nebraska Medical Center, 
      Department of Internal Medicine, Section of Rheumatology, 983025 Nebraska Medical 
      Center, Omaha, NE 68198-3025, USA.
FAU - Thiele, Geoffrey M
AU  - Thiele GM
FAU - Duryee, Michael J
AU  - Duryee MJ
FAU - Schaffert, Courtney S
AU  - Schaffert CS
FAU - DeVeney, Amy L
AU  - DeVeney AL
FAU - Hunter, Carlos D
AU  - Hunter CD
FAU - Olinga, Peter
AU  - Olinga P
FAU - Tuma, Dean J
AU  - Tuma DJ
LA  - eng
GR  - R37 AA007818/AA/NIAAA NIH HHS/United States
GR  - R21 AA15505-01A2/AA/NIAAA NIH HHS/United States
GR  - R01 AA010435/AA/NIAAA NIH HHS/United States
GR  - R21 AA015505-02/AA/NIAAA NIH HHS/United States
GR  - R21 AA015505/AA/NIAAA NIH HHS/United States
GR  - R37 AA07818/AA/NIAAA NIH HHS/United States
GR  - R01 AA010435-11/AA/NIAAA NIH HHS/United States
GR  - R01 AA10435/AA/NIAAA NIH HHS/United States
GR  - R37 AA007818-17/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080521
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Triglycerides)
RN  - 3K9958V90M (Ethanol)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.1.1.1 (Alcohol Dehydrogenase)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Alcohol Dehydrogenase/metabolism
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cytochrome P-450 CYP2E1/metabolism
MH  - *Disease Models, Animal
MH  - Ethanol/*toxicity
MH  - In Vitro Techniques
MH  - *Liver/drug effects/enzymology/pathology
MH  - *Liver Diseases, Alcoholic/enzymology/etiology/pathology
MH  - Male
MH  - Oxidation-Reduction
MH  - *Rats
MH  - Rats, Wistar
MH  - Triglycerides/metabolism
PMC - PMC2845461
MID - NIHMS60598
EDAT- 2008/07/05 09:00
MHDA- 2008/08/05 09:00
PMCR- 2010/03/25
CRDT- 2008/07/05 09:00
PHST- 2008/02/25 00:00 [received]
PHST- 2008/05/07 00:00 [revised]
PHST- 2008/05/08 00:00 [accepted]
PHST- 2008/07/05 09:00 [pubmed]
PHST- 2008/08/05 09:00 [medline]
PHST- 2008/07/05 09:00 [entrez]
PHST- 2010/03/25 00:00 [pmc-release]
AID - S0006-2952(08)00334-1 [pii]
AID - 10.1016/j.bcp.2008.05.012 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2008 Aug 1;76(3):426-36. doi: 10.1016/j.bcp.2008.05.012. Epub 
      2008 May 21.