The antinephritic effects of
PGE1, TEI-5178 and
TEI-6122 on crescentic-type anti-glomerular basement membrane (GBM)
nephritis in rats were investigated. The test compounds were subcutaneously administered every day for 39 days after the injection of
anti-GBM serum.
PGE1 (2.0 mg/kg/day), TEI-5178 (0.25 or 0.5 mg/kg/day) and
TEI-6122 (0.25 or 0.5 mg/kg/day) significantly reduced urinary
protein by 30 to 50% of that of the control at the late stage of
nephritis. These test compounds also suppressed the increase of blood
urea nitrogen and the development of alteration in the glomeruli by the 40th day. Both TEI-5178 (0.5 mg/kg/day) and
TEI-6122 (0.5 mg/kg/day) significantly suppressed the production of antibody to rabbit
gamma-globulin in nephritic rats. This was not the case with
PGE1, however. In additional experiments to clarify the antinephritic mechanisms of the test compounds, it was found that 15 min after one
subcutaneous injection of
PGE1 (1.0 mg/kg), TEI-5178 (0.5 mg/kg) or
TEI-6122 (0.5 mg/kg), systolic blood pressure in the nephritic rats was transiently reduced by 50 to 60%. On the other hand, these test compounds augmented renal blood flow (20-50%) from 45 min after the injection. The relationship between the antinephritic effect and these subsequent findings will be discussed.