Linked Life Data

8072241

Source:http://linkedlifedata.com/resource/pubmed/id/8072241

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-9-27
pubmed:abstractText
Three hours following injection of anti-GBM (glomerular basement membrane) antibody (10 mg/kg, i.v.) into rats, glomerular production of LTB4 was significantly increased as compared to untreated rats (497 +/- 26 vs. 244 +/- 18 pg of LTB4/mg protein). Twenty-four hours following administration of anti-GBM antibody, renal function (blood urea nitrogen, BUN; plasma creatinine, PCr; creatinine clearance, CCr; fractional excretion of sodium, FENa; fractional excretion of urea, FEUrea) was determined to be impaired proportionally to the amount of injected antibody (5 to 30 mg/kg, i.v.). In a second series of experiments, a selective 5-lipoxygenase (5-LO) inhibitor, SK&F 107649, was used to investigate the involvement of 5-LO products in the pathophysiology of anti-GBM antibody-induced glomerulonephritis. In preliminary experiments. SK&F 107649 (50 to 200 mg/kg, p.o.) inhibited ionophore (A23187)-stimulated whole blood leukotriene (LT) B4 production in a dose-dependent fashion (P < 0.05 at doses > or = 100 mg/kg). The anti-GBM antibody-mediated decrease in glomerular filtration rate (GFR) and increase in BUN and PCr were dose-dependently attenuated by SK&F 107649 (50 to 200 mg/kg, p.o. BID). These data confirm that glomerular LTB4 production is stimulated in anti-GBM antibody-induced glomerulonephritis, and demonstrate that inhibition of 5-LO by SK&F 107649 normalizes BUN and PCr and attenuate the decrease in GFR following anti-GBM antibody treatment. These results provide additional evidence for a role of 5-LO products in immune-mediated renal disease, and suggest that pharmacologic inhibition of 5-LO may be of therapeutic value.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1301-10
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat.
pubmed:affiliation
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
pubmed:publicationType
Journal Article