Effect of DP-1904, a thromboxane A 2 synthetase inhibitor, on crescentic nephritis in rats

Abstract

The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane A 2 synthetase inhibitor, was compared with that of OKY-046, using an experimental model of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Test drugs were given p.o. once daily from the day after the anti-glomerular basement membrane serum injection to the 40th day. DP-1904 (5, 15 and 45 mg/kg per day) markedly inhibited the development of glomerular alteration as well as the elevation of proteinuria and plasma cholesterol. On the other hand, OKY-046 (20 mg/kg per day), a thromboxane A 2 synthetase inhibitor, significantly inhibited only deterioration in the glomeruli. DP-1904 and OKY-046 inhibited glomerular thromboxane B 2 production and increased glomerular prostaglandin E 2 and 6-keto prostaglandin F 1α production in normal and nephritic rats. Both drugs inhibited the increase in platelet aggregability, restored decreased renal tissue blood flow to a near-normal level and decreased the deposition of rat immunoglobulin G on glomerular basement membrane in nephritic rats. These results suggest that DP-1904 may be an effective agent for the treatment of proliferative glomerulonephritis.