PMID- 9035283
OWN - NLM
STAT- MEDLINE
DCOM- 19970509
LR  - 20190914
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 7
IP  - 2
DP  - 1997 Feb
TI  - Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with 
      suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and 
      protection against endotoxin-induced liver injury.
PG  - 90-6
AB  - The effect of the free radical scavenger dimethyl sulfoxide (DMSO) on activation 
      of the nuclear transcription factor kappa B (NF-kappa B) was investigated in an 
      experimental model of endotoxin-induced liver failure. In 
      galactosamine-sensitized C3Heb/FeJ mice, DMSO (10 mL/kg) effectively inhibited 
      endotoxin-induced hepatic NF-kappa B activation, suppressed TNF-alpha levels in 
      plasma by 86%, attenuated intercellular adhesion molecule-1 (ICAM-1) mRNA 
      formation, blocked hepatic neutrophil accumulation by 79%, and reduced liver 
      injury by 80%. In galactosamine-sensitized mice treated with 20 micrograms/kg 
      murine TNF-alpha, DMSO moderately reduced hepatic NF-kappa B and decreased ICAM-1 
      mRNA formation and liver injury by 83%, but had no significant effect on hepatic 
      neutrophil accumulation. Thus, DMSO was able to inhibit, at least in part, two 
      critical NF-kappa B-dependent steps in the pathophysiology, i.e., TNF-alpha 
      formation and ICAM-1 gene transcription. Our data suggest the involvement of 
      redox-sensitive events in the signal transduction pathway of NF-kappa B 
      activation in the liver. Inhibition of NF-kappa B activation correlates with the 
      reduced activation of proinflammatory genes in vivo and the subsequent 
      attenuation of inflammatory liver injury. Thus, antioxidants that are NF-kappa B 
      inhibitors may have therapeutic potential in endotoxin shock and sepsis.
FAU - Essani, N A
AU  - Essani NA
AD  - Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007, USA.
FAU - Fisher, M A
AU  - Fisher MA
FAU - Jaeschke, H
AU  - Jaeschke H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Endotoxins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
CIN - Shock. 1997 Feb;7(2):97. PMID: 9035284
MH  - Administration, Topical
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Aspartate Aminotransferases/blood
MH  - Dimethyl Sulfoxide/*pharmacology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Endotoxins/*toxicity
MH  - Galactosamine/pharmacology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
MH  - Intercellular Adhesion Molecule-1/*genetics
MH  - Liver/*drug effects/enzymology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Neutrophils/metabolism
MH  - *Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - 10.1097/00024382-199702000-00003 [doi]
PST - ppublish
SO  - Shock. 1997 Feb;7(2):90-6. doi: 10.1097/00024382-199702000-00003.