In vivo effect of OPC15161, a superoxide scavenger, on anti-Thy1 nephritis

The in vivo effect of 6-(1 H-indol-3-ylmethyl)-5-methoxy-3-(2-methylpropyl)-2(1 H)-pyrazinone, 4-oxide (OPC15161), a superoxide scavenger, was studied in rats with anti-Thy1 nephritis. Rats were divided into 4 groups: G-1, normal control; G-2, anti-Thy1 nephritis; G-3 anti-Thy1 nephritis and treated with OPC15161 (50 mg/kg/day) starting at day 0; and G-4, anti-Thy1 nephritis and treated with OPC15161 starting 3 days before antibody injection. At weeks 2 and 8, rats were killed for morphological study and at week 8 for renal clearance. Results were compared among the 4 groups. OPC15161 suppressed urinary albumin/day. Total glomerular cells, mesangial cells, ED-1-positive cells/glomerulus and glomerular volume all increased and the increases were suppressed by OPC15161. Tubulointerstitial index, assessed by point counting, was improved by OPC15161 (P < 0.05 G-3, 4, vs. G-2, not significant vs. G-1). Glomerular filtration rate decreased in all nephritic animals, but the decrease in renal blood flow was less in the treated groups. These findings indicate a favorable effect of OPC15161 on the glomerular and interstitial lesions of anti-Thy1 nephritis.