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The effects of R-75,317 on antiglomerular basement membrane glomerulonephritis in rats

  • PAF and the Renal System
  • Published:
Lipids

Abstract

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.

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Abbreviations

AA:

arachidonic acid

Ccr:

creatinine clearance

GBM:

glomerular basement membrane

GFR:

glomerular filtration rate

NAG:

N-acetyl-β-D-glucosaminidase

PAF:

plateletactivating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine

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Authors and Affiliations

  1. New Lead Research Laboratories, Sankyo Co., Ltd., 140, Tokyo, Japan

    Yasuteru Ijima

  2. Fermentation Research Laboratories, Sankyo Co., Ltd., 140, Tokyo, Japan

    Norio Nakamura

  3. Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, 140, Tokyo, Japan

    Masaaki Miyamoto, Hiroyuki Koike, Toshio Sada & Junichiro Fukushige

Authors
  1. Masaaki Miyamoto
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  2. Hiroyuki Koike
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  3. Toshio Sada
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  4. Yasuteru Ijima
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  5. Junichiro Fukushige
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  6. Norio Nakamura
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Miyamoto, M., Koike, H., Sada, T. et al. The effects of R-75,317 on antiglomerular basement membrane glomerulonephritis in rats. Lipids 26, 1316–1319 (1991). https://doi.org/10.1007/BF02536556

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  • DOI: https://doi.org/10.1007/BF02536556

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