Antiproteinuric effect of a thromboxane receptor antagonist, S-1452, on rat diabetic nephropathy and murine lupus nephritis

Pharmacology. 1995 Jan;50(1):1-8. doi: 10.1159/000139261.

Abstract

To shed light on the role of thromboxane A2 (TXA2) in renal injury, we evaluated the effects of S-1452, a TXA2 receptor antagonist, on rats with streptozotocin (STZ)-induced diabetic nephropathy and murine lupus nephritis. In STZ diabetes rats (n = 6), urinary protein excretion significantly increased from 8 weeks and was about 5 times as much 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 observed and was significantly inhibited at 8 and 10 weeks after induction of diabetes. In (NZB x NZW)F1 mice, no proteinuria was detected in vehicle controls (n = 20) and S-1452-treated mice (n = 20) from 0 to 8 weeks after initiation of S-1452 treatment. Proteinuria was observed in 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively. Proteinuria developed more slowly in S-1452-treated mice than in vehicle controls. In conclusion, TXA2 receptor antagonist, S-1452, suppresses the progression of renal injury.

MeSH terms

  • Acetylglucosaminidase / blood
  • Animals
  • Blood Glucose / drug effects
  • Bridged Bicyclo Compounds / pharmacology*
  • Cholesterol / blood
  • Creatinine / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Fatty Acids, Monounsaturated / pharmacology*
  • Female
  • Lupus Nephritis / drug therapy
  • Male
  • Mice
  • Mice, Inbred NZB
  • Proteinuria / prevention & control*
  • Rats
  • Rats, Wistar
  • Receptors, Thromboxane / antagonists & inhibitors*

Substances

  • Blood Glucose
  • Bridged Bicyclo Compounds
  • Fatty Acids, Monounsaturated
  • Receptors, Thromboxane
  • S 145
  • Cholesterol
  • Creatinine
  • Acetylglucosaminidase