PMID- 9655692
OWN - NLM
STAT- MEDLINE
DCOM- 19980825
LR  - 20190322
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 275
IP  - 1
DP  - 1998 Jul
TI  - S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced 
      hepatic injury.
PG  - G125-9
LID - 10.1152/ajpgi.1998.275.1.G125 [doi]
AB  - S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline. 
      Adomet deficiency occurs in certain types of liver injury, and the injury is 
      attenuated by exogenous Adomet. Tumor necrosis factor-alpha (TNF-alpha) is also a 
      mediator of these models of hepatotoxicity. We investigated the role of Adomet in 
      lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both 
      Adomet and choline. Rats were maintained on either a methionine-restricted and 
      choline-deficient (MCD) diet or a diet containing sufficient amounts of all 
      nutrients [methionine and choline sufficient (MCS)] and then administered either 
      LPS or saline. MCS-LPS rats had normal liver histology and no change in serum 
      transaminases compared with the MCS-saline control group. MCD-saline rats had 
      hepatosteatosis but no necrosis, and a five- to sevenfold increase in 
      transaminases vs. the MCS-saline group. MCD-LPS rats additionally had 
      hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet 
      administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not 
      of choline, prevented necrosis but not steatosis, and attenuated transaminases. 
      Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 
      300-fold higher with LPS challenge. Exogenous Adomet attenuated increased serum 
      TNF-alpha in MCD-LPS rats.
FAU - Chawla, R K
AU  - Chawla RK
AD  - Department of Internal Medicine, College of Medicine, University of Kentucky, 
      Lexington, Kentucky 40536, USA.
FAU - Watson, W H
AU  - Watson WH
FAU - Eastin, C E
AU  - Eastin CE
FAU - Lee, E Y
AU  - Lee EY
FAU - Schmidt, J
AU  - Schmidt J
FAU - McClain, C J
AU  - McClain CJ
LA  - eng
GR  - AA-08565/AA/NIAAA NIH HHS/United States
GR  - AA-10496/AA/NIAAA NIH HHS/United States
GR  - MO1-RR2602/RR/NCRR NIH HHS/United States
PT  - Journal Article
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 Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Choline Deficiency/pathology/*physiopathology
MH  - Glutathione/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Liver/drug effects/metabolism/*pathology
MH  - Male
MH  - Methionine/deficiency
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - S-Adenosylmethionine/*deficiency/pharmacology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1998/07/09 00:00
MHDA- 1998/07/09 00:01
CRDT- 1998/07/09 00:00
PHST- 1998/07/09 00:00 [pubmed]
PHST- 1998/07/09 00:01 [medline]
PHST- 1998/07/09 00:00 [entrez]
AID - 10.1152/ajpgi.1998.275.1.G125 [doi]
PST - ppublish
SO  - Am J Physiol. 1998 Jul;275(1):G125-9. doi: 10.1152/ajpgi.1998.275.1.G125.