Antinephritic effect of Y-19018, a thromboxane A synthetase inhibitor, on crescentic-type anti-GBM nephritis in rats.
In order to investigate the antinephritic effect of Y-19018, a thromboxane A synthetase inhibitor, on crescentic-type anti-glomerular basement membrane (anti-GBM) nephritis in rats, the present study was undertaken. Male Sprague Dawley rats were immunized with rabbit gamma-globulin in Freund's complete adjuvant following i.v. injection of anti-GBM serum. Y-19018 at a dose of 0.3 and 3.0 mg/kg was given orally to rats from the day after the injection of anti-GBM serum (day 1) to day 39. Y-19018, 3.0 mg/kg, significantly inhibited both urinary protein excretion (30.6%) on day 19 and plasma cholesterol (39.8%) on day 15. Moreover, light microscopy demonstrated that this drug at both doses remarkably prevented histological involvement of the glomeruli on day 40 in a dose-dependent manner. In the blood obtained from nephritic rats, platelet aggregation was increased. Y-19018 suppressed (48.7%) the hyperaggregability of platelets on day 40 at a high dose, although the suppression of platelet aggregation was not in a dose-dependent manner. It is concluded from these data that Y-19018 shows beneficial effects on crescentic-type anti-GBM nephritis and may exert its action partly through inhibition of glomerular TXA2.
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Y
Y
Suzuki
Y
Y
Tsukushi
M
M
Ito
T
T
Nagamatsu
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology; D007093:Imidazoles / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; C054964:Y 19018; D002784:Cholesterol; D000118:Acetylglucosaminidase; D013930:Thromboxane-A Synthase