Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat.
We investigated the effects of YM264, WEB2086, methylprednisolone and ticlopidine on puromycin-induced nephropathy in the rat. Puromycin produces marked proteinuria, hypercholesterolemia, and hypoalbuminemia. The structurally differing PAF antagonists YM264 and WEB2086 inhibited proteinuria and improved hypercholesterolemia and hypoalbuminemia. Methylprednisolone also exhibited a beneficial effect on these variables. However, ticlopidine, a platelet inhibitor, showed no inhibitory effect on nephropathy. These results indicate that PAF may play a major role in puromycin-induced nephropathy in the rat, and that PAF antagonists may prove of therapeutic value in the treatment of nephropathy in humans.
Yamada
T
T
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Tomioka
K
K
Horie
M
M
Sakurai
Y
Y
Nagaoka
H
H
Mase
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000188:drug therapy*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011507:Proteinuria / Q000517:prevention & control; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013988:Ticlopidine / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010879:Piperazines; D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; D014230:Triazoles; C052518:WEB 2086; C068679:YM 264; D011692:Puromycin Aminonucleoside; D013988:Ticlopidine; D008775:Methylprednisolone