T. Nagao et al., EFFECT OF DP-1904, A THROMBOXANE A(2) SYNTHASE INHIBITOR, ON PASSIVE HEYMANN NEPHRITIS IN RATS, European journal of pharmacology, 316(1), 1996, pp. 73-80
The antinephritic effect of DP-1904 methyl)-5,6,7,8-tetrahydronaphthal
ene-2-carboxylic acid hydrochloride], a thromboxane A(2) synthase inhi
bitor, was evaluated using an experimental model of membranous nephrop
athy, viz. accelerated passive Heymann nephritis in which the glomerul
ar injury is mediated by immune complexes. DP-1904 markedly inhibited
the development of glomerular alteration as well as the elevation of p
roteinuria and plasma creatinine. When the treatment was started from
the 22nd day, at which time proteinuria is fully developed, DP-1904 sh
owed beneficial effects on proteinuria and glomerular histopathologica
l changes. DP-1904 apparently decreased the deposition of both rabbit
immunoglobulin G and rat immunoglobulin G on glomerular basement membr
ane in nephritic rats. A single administration of DP-1904 restored the
decreased renal tissue blood flow, inhibited glomerular thromboxane B
-2 production and increased glomerular prostaglandin E(2) and 6-keto p
rostaglandin F-1 alpha production in nephritic rats. These results sug
gest that DP-1904 may be an effective agent for the treatment of idiop
athic membranous nephropathy and that the beneficial effect of this dr
ug may be due to the elimination of glomerular immune deposits and to
an increase in renal tissue blood flow related to amelioration of the
abnormal metabolism of arachidonic acid.