THERAPEUTIC EFFECT OF A NEWLY DEVELOPED ANTIOXIDATIVE AGENT (OPC-15161) ON EXPERIMENTAL IMMUNE-COMPLEX NEPHRITIS

The effect of a newly developed free radical scavenger (OPC-15161) on the progression of nephrotoxic serum (NTS) nephritis was evaluated. NT S nephritis rats were sacrificed immediately before and 1, 2, 3, 6, an d 24 h and 13 and 19 days after intravenous injection of NTS, The tiss ue content of phosphatidylcholine hydroperoxide, the activity of super oxide, the activity of superoxide dismutase in the renal cortex, and t he serum malondialdehyde levels were measured. The phosphatidylcholine hydroperoxide content in the renal cortex of OPC-15161-treated NTS ne phritis rats was lower than that in the control rats 24 h after NTS in jection. The activity of superoxide dismutase in OPC-15161-treated rat s was sustained in contrast to the decrease in this activity in the co ntrol rats 6 h after injection of NTS. The effects of OPC-15161, dipyr idamole, and prednisolone on NTS nephritis rats were investigated. OPC -15161 (20 mg/kg p.o.) showed a potent inhibitory effect on the urinar y protein excretion, whereas dipyridamole (30 and 100 mg/kg p.o.) and prednisolone (2 mg/kg p.o.) had less suppressive effects. In view of t hese results, we conclude that OPC-15161 notably ameliorated the urina ry protein excretion by way of the suppression of lipid peroxidation i n the renal tissue of NTS nephritis rats.