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The effects of R‐75,317 on antiglomerular basement membrane glomerulonephritis in rats
Author(s) -
Miyamoto Masaaki,
Koike Hiroyuki,
Sada Toshio,
Ijima Yasuteru,
Fukushige Junichiro,
Nakamura Norio
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536556
Subject(s) - basement membrane , basement , glomerulonephritis , chemistry , lipidology , clinical chemistry , medicine , pathology , biochemistry , kidney , history , archaeology
Platelet‐activating factor (PAF) is a potent inflammatory mediator which is released by various inflammatory cells and produced by certain tissues, including the kidney. PAF has been shown to increase glomerular permeability to protein and to decrease glomerular filtration rate (GFR) by contracting mesangium. On the basis of these observations, it has been suspected that PAF may play a role as mediator of glomerular damage in glomerular nephritis. To examine this possibility, we studied the effects of a specific PAF antagonist, R‐75,317, on the development of an experimental model of anti‐glomerular basement membrane (anti‐GBM) glomerulonephritis. Glomerulonephritis was initiated by injecting rabbit anti‐rat GBM serum into rats. Proteinuria gradually developed after serum injection, plateaued at week 2, and remained at the high level of week 2 throughout the experimental period (6 wk). Chronic treatment with R‐75,317 (10 mg/kg/day i.p.) tended to delay the onset of proteinuria and significantly accelerated the recovery phase. Creatinine clearance (Ccr) fell to 40% at week 3. R‐75,317 treatment completely prevented this decline of Ccr. Histological changes in this model (glomerular hypertrophy, proliferation of mesangial matrix and interstitial fibrosis) were also ameliorated by the R‐75,317 treatment. The results suggest that PAF may play a role in the development of glomerulonephritis and that PAF antagonists could be used in the treatment of human renal disease.