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.