[Effects of YM-13650 on experimental nephritis in rats and mice]

We investigated the effects of YM-13650, 2-(m-carboxyacetoxyphenyl) imidazo [2, 1-b] benzothiazole, on BSA-immune complex nephritis in rats and lupus nephritis in NZB/W F1 mice. In preventative experiments on immune complex nephritis in rats, YM-13650 (10 approximately 100 mg/kg, p.o.) dose-dependently inhibited the increase in urinary protein, serum cholesterol, and urea nitrogen. Histopathological observation showed striking hypercellularity and mesangial widening in nephritic control; however, glomerular injury was reduced in YM-13650-treated animals. In therapeutic study, control rats maintained high levels of urinary protein, serum cholesterol and urea nitrogen throughout the experimental period. These variables were lower in YM-13650-treated rats. In preventative experiments in lupus mice treated from 8 weeks of age, YM-13650 in comparison with the control group showed a lesser degree of proteinuria throughout the experimental period. It also significantly prolonged or tended to prolong the life span of NZB/W F1 mice compared with the control. In therapeutic experiments conducted after the onset of lupus nephritis in mice, the drug also inhibited an increase in urinary protein and tended to prolong the life span. These results show that YM-13650 has preventative and therapeutic effects on experimental nephritis in rats and mice, and it may prove valuable as an anti-nephritic drug.