Antinephritic Effect of Y-19018, a Thromboxane A Synthetase Inhibitor, on Crescentic-Type Anti-GBM Nephritis in Rats

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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 γ-globulin in Freunds 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 TXA<SUB>2</SUB>.