Studies on antinephritic effect of mizoribine (p-INN, Bredinin), a new immunosuppressive agent, and azathioprine (1) effect on the nephrotic type of anti-GBM nephritis in rats

The present study was made to investigate the antinephritic effect of mizoribine in comparison to that of azathioprine by using the nephrotic type of anti-rat glomerular basement membrane rabbit serum (anti-GBM serum)-induced nephritis in rats. The nephrotic type nephritis was induced in rats by two i.v. injections of anti-GBM serum at a 10 day interval. Both drugs were given orally, daily from the 2nd day following the first injection of anti-GBM serum to the 21st day. Mizoribine in doses of 5 and 7.5 mg/kg/day significantly inhibited urinary protein excretion by 30-40% on the 22nd day. Mizoribine at both doses showed an inhibitory tendency on urinary alkaline phosphatase (ALP) excretion on the 9th and 16th days. On the 22nd day, this drug at a dose of 7.5 mg/kg/day inhibited plasma cholesterol (CL) content by 59.6% and wet weight of kidneys by approx. 50%, but no significant difference was seen between the drug-treated and control groups. When renal tissues on the 22nd day were observed under light microscopy, mizoribine at both doses remarkably prevented glomerular changes such as mesangial proliferation and thickening of capillary walls and significantly inhibited the index of glomerular lesions (IGL) by over 60%. On the other hand, azathioprine at a dose of 20 mg/kg/day was as effective as mizoribine at 5 mg/kg/day in inhibiting urinary protein and ALP excretions, plasma CL content and kidney weight. However, azathioprine showed little effect on the IGL. From these results, mizoribine at the dose level of 1/4 to 1/3 of azathioprine showed a more potent effect than azathioprine in this model. Therefore, mizoribine is also expected to have a beneficial effect on nephrotic type nephritis in clinical fields.