PMID- 10869469
OWN - NLM
STAT- MEDLINE
DCOM- 20000810
LR  - 20190513
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 56
IP  - 1
DP  - 2000 Jul
TI  - Pentoxifylline attenuates bacterial lipopolysaccharide-induced enhancement of 
      allyl alcohol hepatotoxicity.
PG  - 203-10
AB  - Small amounts of exogenous lipopolysaccharide (LPS) (10 ng/kg-100 microg/kg) 
      enhance the hepatotoxicity of allyl alcohol in male Sprague-Dawley rats. This 
      augmentation of allyl alcohol hepatotoxicity appears to be linked to Kupffer cell 
      function, but the mechanism of Kupffer cell involvement is unknown. Since Kupffer 
      cells produce tumor necrosis factor-alpha (TNF alpha) upon exposure to LPS, and 
      this cytokine has been implicated in liver injury from large doses of LPS, we 
      tested the hypothesis that TNF alpha contributes to LPS enhancement of allyl 
      alcohol hepatotoxicity. Rats were treated with LPS (10-100 microg/kg iv) 2 h 
      before allyl alcohol (30 mg/kg ip). Co-treatment with LPS and allyl alcohol 
      caused liver injury as assessed by an increase in activity of alanine 
      aminotransferase in plasma. Treatment with LPS caused an increase in plasma TNF 
      alpha concentration, which was prevented by administration of either 
      pentoxifylline (PTX) (100 mg/kg iv) or anti-TNF alpha serum (1 ml/rat iv) one h 
      prior to LPS. Only PTX protected rats from LPS-induced enhancement of allyl 
      alcohol hepatotoxicity; anti-TNF alpha serum had no effect. Exposure of cultured 
      hepatocytes to LPS (1-10 microg/ml) or to TNF alpha (15-150 ng/ml) for 2 h did 
      not increase the cytotoxicity of allyl alcohol (0.01-200 microM). These data 
      suggest that neither LPS nor TNF alpha alone was sufficient to increase the 
      sensitivity of isolated hepatocytes to allyl alcohol. Furthermore, hepatocytes 
      isolated from rats treated 2 h earlier with LPS (i.e., hepatocytes which were 
      exposed in vivo to TNF alpha and other inflammatory mediators) were no more 
      sensitive to allyl alcohol-induced cytotoxicity than hepatocytes from naive rats. 
      These data suggest that circulating TNF alpha is not involved in the mechanism by 
      which LPS enhances hepatotoxicity of allyl alcohol and that the protective effect 
      of PTX may be due to another of its biological effects.
FAU - Sneed, R A
AU  - Sneed RA
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, Michigan 48824, USA.
FAU - Buchweitz, J P
AU  - Buchweitz JP
FAU - Jean, P A
AU  - Jean PA
FAU - Ganey, P E
AU  - Ganey PE
LA  - eng
GR  - ES08789/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Propanols)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3W678R12M0 (allyl alcohol)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Antibodies, Blocking/pharmacology
MH  - Cells, Cultured
MH  - Chemical and Drug Induced Liver Injury/blood/*etiology
MH  - Drug Synergism
MH  - Escherichia coli
MH  - Kupffer Cells/drug effects/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Liver/cytology/*drug effects/metabolism
MH  - Male
MH  - Pentoxifylline/*pharmacology
MH  - Propanols/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism/pharmacology
EDAT- 2000/06/28 11:00
MHDA- 2000/08/12 11:00
CRDT- 2000/06/28 11:00
PHST- 2000/06/28 11:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 2000/06/28 11:00 [entrez]
AID - 10.1093/toxsci/56.1.203 [doi]
PST - ppublish
SO  - Toxicol Sci. 2000 Jul;56(1):203-10. doi: 10.1093/toxsci/56.1.203.