Effects of KW-3635, a specific thromboxane A2-receptor antagonist, on the development of lupus nephritis in NZB x NZW F1 mice.
We examined the effect of KW-3635, a specific thromboxane A2 (TXA2)-receptor antagonist, on the development of lupus nephritis in NZB x NZW F1 mice. KW-3635 was orally given once a day for 33 weeks beginning at eight weeks of age. In the control group, the mice began to die at 39 weeks of age, showing severe proteinuria and histopathologic abnormality in the renal glomeruli. Administration of KW-3635 (30 mg/kg/day) significantly reduced urinary protein excretion (1.7 +/- 0.9 vs. 8.5 +/- 2.4 mg/6 hr/mouse, P < 0.01), mortality (1/18 vs. 6/19, P < 0.05) and the histopathologic score of the kidney examined at 41 weeks of age. Thus, chronic administration of KW-3635 markedly attenuated the renal disease in NZB x NZW F1 mice, suggesting that TXA2 is an important mediator of the pathogenesis in this murine model of lupus nephritis.
Kawakage
M
M
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Mizumoto
H
H
Nukui
E
E
Sato
S
S
Karasawa
A
A
D000284:Administration, Oral; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001584:Benzoxepins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D011507:Proteinuria / Q000188:drug therapy; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000502:physiology
D000974:Antibodies, Antinuclear; D001562:Benzimidazoles; D001584:Benzoxepins; D013928:Thromboxane A2; C065729:KW 3635