Effects of leflunomide on glomerulonephritis induced by antibasement membrane antibody in rats

Abstract

Leflunomide (HWA 486, a novel isoxazol derivative), shown to have potent immunosuppressant and antiinflammatory effects, was evaluated for its inhibitory and therapeutic effects on the glomerulonephritis induced in rats by rabbit antiserum against rat glomerular basement membrane. Leflunomide was administered orally to rats at 0.5 and 2 mg/kg/day for 20 days from 2 days before injection of the rabbit antiserum and at 2 mg/kg/day for 14 days from 5 days after the antibody injection. The present study consisting of 2 experiments for inhibitory (I) and therapeutic (II) effects of leflunomide revealed the following effects at 2 mg/kg: in experiment I, significant decreases in (a) urinary total protein, (b) plasma total cholesterol and fibrinogen and (c) thymus weight, and decreased incidences of fibrin deposits in Bowman's space, adhesion of the glomerulus to Bowman's capsule and deposition of rat IgG and C₃; and in experiment II, decreases in (a), (b) and (c), though smaller than in experiment I, and decreases deposition of rat C₃. Thus, leflunomide had potent inhibitory and limited therapeutic effects on glomerulonephritis, suggesting that the compound is effective in inhibiting the onset and development of glomerulonephritis.