Evidence suggesting a role for platelet-activating factor (PAF) in experimental nephrotic syndrome.
Sprague-Dawley rats injected with a single dose of adriamycin at 7.5 mg/kg/day developed an important and persistent proteinuria from day 14. Animals treated from day 0 to 3 weeks with PAF-receptor antagonists (BN 52021 or alprazolam) did not present (p less than 0.0005) the adriamycin-induced proteinuria or only to a very low extent. Furthermore, epithelial glomerular cells presented in these animals a normal aspect, while in rats injected with adriamycin, but not treated, the epithelial cells showed effacement of foot processes and intensive degenerative changes. By contrast, rats treated with steroids or cyclosporin did not present a significant reduction in proteinuria or improvements in epithelial cell lesions. Rats injected with adriamycin also presented an increase in the number of inflammatory infiltrating cells, chiefly la(+)-reactive cells (OX6+ cells), macrophages (ED1+ cells) and T-cytotoxic/suppressor cells (OX8+ cells). Concomitant administration of PAF-receptor antagonists induced a significant reduction in the number of these cells. Glomerular cells from normal control rats incubated with adriamycin incorporated 3H-acetate into a polar lipid with biological and migratory characteristics on thin-layer chromatography similar to synthetic PAF. On the whole, our data suggest a role for PAF in the pathogenesis of experimental nephrotic syndrome induced by adriamycin.
Egido
J
J
Servizio de Nefrologia, Fundación Jiménez Díaz, Madrid, Spain.
Mampaso
F
F
Gómez-Chiarri
M
M
González
E
E
Ortíz
A
A
Lerma
J L
JL
Robles
A
A
Braquet
P
P
Hernando
L
L
D000085:Acetates / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D013997:Time Factors
D000085:Acetates; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D004317:Doxorubicin