Regulation of Free Radical Production in Experimental Renal Disease

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To investigate substantial role of free radical (reactive oxygen species (ROS)) in the pathogenesis of experimental glomerula injury, glomerular chemiluminescence (GCL) assay were performed in rat experimental renal diseases together with treatment with radical scavengers. In glomerulonephritis, cell kinetics using histochemistry were studied along with GCL assay. In anti-glomerular basement membrane glomerulonephritis, GCL increased reflecting ROS generation due to activated polymorphonuclear leukocyte (PMN) or macrophage infiltrated in glomerulus. Protective effect on proteinuria and decrease of creatinine clearance were noted in rats with catalase or SOD treatment during the phase of PMN infiltration. In anti-Thy-1 nephritis, ROS production was consistent with macrophage infiltration. On the other hand glomeruli from puromycin aminonucleoside (PAN) or adriamycin nephrosis rat, showed also increase of GCL suggesting ROS production from glomerular resident cells. Suppression of increased GCL in PAN by radical scavenger, dipyridamole and dilazep, which reportedly have protective effect on PAN nephrosis, indicated that antioxidant can play a role in the therapy of glomerular lesion. These results also elucidated that these scavengers should be administered concomitantly with ROS generating phase from the infiltrating cells and/or glomerular resident cells.