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 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.
Matsuo
Y
Y
Developmental Research Laboratories, Osaka, Japan.
Takagawa
I
I
Koshida
H
H
Kawabata
T
T
Nakamura
M
M
Ida
T
T
Zhou
L
L
Marumo
F
F
D000118:Acetylglucosaminidase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D008181:Lupus Nephritis / Q000188:drug therapy; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D017482:Receptors, Thromboxane; C056566:S 145; D002784:Cholesterol; D003404:Creatinine; D000118:Acetylglucosaminidase