Studies on antinephritic effect of mizoribine (p-INN, Bredinin), a new immunosuppressive agent, and azathioprine. (2) Effect on crescentic-type anti-GBM nephritis in rats.

Crescentic-type nephritis was induced in rats by immunizing with rabbit gamma-globulin following i.v. injection of rabbit anti-rat glomerular basement membrane (anti-GBM) serum. The antinephritic effect of mizoribine was compared to that of azathioprine by administration from the 2nd day after the injection of anti-GBM serum to the 23rd day (Experiment I) and from the 15th to the 38th day (Experiment II). The experiment I assessment on the 24th day revealed that mizoribine at a dose of 7.5 mg/kg/day p.o. remarkably reduced plasma cholesterol level, wet kidney weight and glomerular histopathological changes (i.e., crescent formation and fibrinoid deposition). In addition, mizoribine at this dose also tended to reduce urinary protein excretion and the adhesion of capillary walls to Bowman's capsule. At a dose of 5 mg/kg/day p.o., mizoribine significantly reduced kidney weight and crescent formation. On the other hand, azathioprine at a dose of 20 mg/kg/day p.o. had a tendency to reduce these biochemical and histopathological parameters. In the experiment II assessment on the 39th day, the effects of both drugs were somewhat diminished compared to those in experiment I. Mizoribine strikingly inhibited the crescent formation with 5 and 7.5 mg/kg/day p.o. and inhibited the fibrinoid deposition with a dose of 7.5 mg/kg/day p.o. Azathioprine at a dose of 20 mg/kg/day p.o. was prone to reduce histopathological parameters. The above data indicate that mizoribine may be a useful new immunosuppressive agent for rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesion with the extensive formation of crescents.