Antinephritic effect of OKY-046, a thromboxane A synthetase inhibitor (1). Effects on crescentic-type anti-GBM nephritis in rats.
To induce crescentic-type anti-glomerular basement membrane (anti-GBM) nephritis, male Sprague-Dawley rats were immunized with rabbit gamma-globulin in Freund's complete adjuvant following i.v. injection of anti-GBM serum. At the same time, original type anti-GBM nephritis was induced in other rats by anti-GBM serum only. The animals with crescentic-type anti-GBM nephritis showed significantly higher platelet aggregability than that in rats with original-type anti-GBM nephritis at days 5, 10 and 40 after anti-GBM serum administration, respectively. To estimate the antinephritic effect of OKY-046, a thromboxane A synthetase inhibitor, it was given orally to rats at doses of 0.5, 2.5 or 20 mg/kg for 39 days after anti-GBM serum. OKY-046 (20 mg/kg) significantly inhibited the increase in both urinary protein and plasma cholesterol levels (40% and 35% vs. control, respectively). Moreover, when examined by light microscopy, this drug remarkably prevented histological involvement of the glomeruli. OKY-046 at 20 mg/kg had suppressed the hyperaggregability of platelets by 77% by day 40 as compared with the control, but doses of 0.5 and 2.5 mg/kg did not. It is concluded from these data that OKY-046 has beneficial effects on crescentic-type anti-GBM nephritis and may act through inhibition of not only platelet TxA2 but also glomerular TxA2 in its action to prevent histological alterations.
Nagamatsu
T
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Tsukushi
Y
Y
Ito
M
M
Kondo
N
N
Suzuki
Y
Y
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005921:Glomerulonephritis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008689:Methacrylates / Q000493:pharmacokinetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014563:Urodynamics / Q000187:drug effects
D000179:Acrylates; D008689:Methacrylates; D010975:Platelet Aggregation Inhibitors; D002784:Cholesterol; D013930:Thromboxane-A Synthase; C034364:ozagrel