Effects of the platelet-activating factor antagonists CV-6209 and CV-3988 on nephrotoxic serum nephritis in the rat.
Platelet-activating factor (PAF) is known as an important mediator in the pathogenesis of glomerular injury. In the present study, we evaluated the effect of the specific PAF antagonists CV-6209 and CV-3988 on accelerated nephrotoxic serum nephritis (NTN) in the rat. The amount of urinary protein excretion was significantly less in the rats treated with CV-6209 or CV-3988 on the 5th and 7th day of treatment than in the nontreated controls. The results of light- and immunofluorescence-microscopic examination did not demonstrate any favorable effect on glomerular changes by these PAF antagonists. However, CV-6209 protected against the loss of glomerular anionic charges in rats with NTN. Thus, it is suggested that PAF is a potent mediator of protein excretion, and that the loss of glomerular anionic charges is an important mechanism for the mediation of PAF in glomerulonephritis.
Iida
H
H
Second Department of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Fujita
M
M
Izumino
K
K
Asaka
M
M
Entani
C
C
Takata
M
M
Sasayama
S
S
D000818:Animals; D000838:Anions; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D011507:Proteinuria / Q000517:prevention & control; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000838:Anions; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; C037913:CV 3988