Mesangiolysis and endothelial lesions due to peroxidative damage in rabbits

There is much evidence that oxygen free radicals (OFR) may be the final mediators of biochemical and molecular damage in many kidney diseases of different etiology (toxic, ischemic and immunologically mediated), involving mainly endothelium, basement membrane and tubular cells, but direct demonstration of a role in inducing mesangiolysis is lacking. An experimental model of renal damage caused by OFR was carried out in 6 rabbits using a mixture of xanthine-oxidase and xanthine, which produces a large amount of the radical superoxide anion. Both enzyme (0.0150 and 0.150 U/ml) and substrate (0.2 and 2 mM) were simultaneously infused in one kidney, while the controlateral kidneys perfused with buffer only were used as controls. Treated kidneys were compared to controls by light and electron microscopy. A further experiment was carried out in 4 other rabbits to evaluate the protection afforded by superoxide dismutase, the specific enzyme-scavenging superoxide anion. Microscopic studies showed dose-related ingravescent damage in the treated kidneys: capillary enlargement, subendothelial swelling, detachment of the endothelium from the basement membrane, mesangiolysis and microaneurysms. Control kidneys appeared to be normal. No significant differences were observed in the kidneys treated with addition of superoxide dismutase. These results are the first direct demonstration of a role of superoxide anion in the induction of mesangiolysis in rabbits. The lack of a protective effect by superoxide dismutase could mean that the superoxide anion triggers a chain of other OFR, further responsible for damage.