Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat
| Autor: | Don E. Griswold, George Dytko, Brian Short, Jerry L. Adams, Bogdan Zabko-Potapovich, Bridget Brickson, Christine R. Albrightson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Fractional excretion of sodium Tetrahydronaphthalenes Kidney Glomerulus Renal function Fluorescent Antibody Technique urologic and male genital diseases Leukotriene B4 Basement Membrane Excretion Rats Sprague-Dawley chemistry.chemical_compound Glomerulonephritis Internal medicine medicine Animals Urea Lipoxygenase Inhibitors Blood urea nitrogen Whole blood Arachidonate 5-Lipoxygenase Sheep Dose-Response Relationship Drug Chemistry urogenital system Glomerular basement membrane medicine.disease Rats Endocrinology medicine.anatomical_structure Nephrology Immunoglobulin G Glomerular Filtration Rate |
| Zdroj: | Kidney International. 45(5):1301-1310 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.1994.170 |
| Popis: | Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat. 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 ± 18pg 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 ≥ 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. |
| Databáze: | OpenAIRE |
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