ANTIPROTEINURIC EFFECT OF A THROMBOXANE RECEPTOR ANTAGONIST, S-1452, ON RAT DIABETIC NEPHROPATHY AND MURINE LUPUS NEPHRITIS

To shed light on the role of thromboxane A(2) (TXA(2)) in renal injury , we evaluated the effects of S-1452, a TXA(2) receptor antagonist, on rats with streptozotocin (STZ)-induced diabetic nephropathy and murin e lupus nephritis. In STZ diabetes rats (n = 6), urinary protein excre tion significantly increased from 8 weeks and was about 5 times as muc h as that in normal rats at 10 weeks after induction of diabetes. In S -1452-treated rats (n = 6), increase in urinary protein was rarely obs erved and was significantly inhibited at 8 and 10 weeks after inductio n of diabetes. In (NZB x NZW)F1 mice, no proteinuria was detected in v ehicle controls (n = 20) and S-1452-treated mice (n = 20) from 0 to 8 weeks after initiation of S-1452 treatment. Proteinuria was observed i n 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1 452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively. Proteinuria developed more slowly in S-1452-treated mic e than in vehicle controls. In conclusion, TXA(2) receptor antagonist, S-1452, suppresses the progression of renal injury.