Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-5-10
pubmed:abstractText
Mice are relatively resistant to the lethal effects of endotoxin. Sensitivity to lipopolysaccharide (LPS) and monophosphoryl lipid A (MPL) can be enhanced by concurrently loading animals with D-galactosamine (D-gal). Significant diurnal variation in susceptibility to lethal toxicity was observed in D-gal loaded mice upon LPS or MPL immunostimulant challenge. In mice treated with either MPL or MPL plus D-gal, at the time of greatest toxic sensitivity, serum TNF levels were significantly higher than was seen in mice treated at a time of low sensitivity. Peritoneal exudate cells (PECs) harvested from mice treated with either D-gal or MPL displayed enhanced in vitro superoxide (SO) production. Simultaneous treatment with D-gal and MPL led to a synergistic enhancement of SO production above that induced by either xenobiotic alone. Pretreatment with the SO dismutase mimetic Cu(II) (diisopropyl salicylate)2 significantly protected mice from the lethal toxicity of D-gal-MPL challenge. PECs harvested from these same mice failed to display the elevated in vitro SO production reported above. SO elaboration in vivo, presumably by hepatocytes, PECs, and possibly other cells, subsequent to D-gal loading and LPS or MPL challenge, appears to play an important role in the lethal toxicity observed. The diurnal variation in toxicity reported in this animal model may result from TNF modulation of SO production in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1053-8550
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-74
pubmed:dateRevised
2008-3-18
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
The D-galactosamine loaded mouse and its enhanced sensitivity to lipopolysaccharide and monophosphoryl lipid A: a role for superoxide.
pubmed:affiliation
Ribi ImmunoChem Research, Inc., Hamilton, Montana 59840.
pubmed:publicationType
Journal Article