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- Title
Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat.
- Authors
Albrightson, Christine R.; Short, Brian; Dytko, George; Zabko-Potapovich, Bogdan; Brickson, Bridget; Adams, Jerry L.; Griswold, Don E.
- Abstract
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, PCrk; creatinine clearance, CCrk; 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&E 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 ⩾ 100 mg/kg). The anti-GBM antibody-mediated decrease in glomerular filtration rate (GFR) and increase in BUN and PCrk 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 PCrk 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.
- Subjects
LIPOXYGENASES; IMMUNOGLOBULINS; GLOMERULONEPHRITIS; UREA; EXCRETION; PATHOLOGICAL physiology
- Publication
Kidney International, 1994, Vol 45, Issue 5, p1301
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.170