THE INFLUENCE OF CYCLOSPORINE ON LIPID-PEROXIDATION AND SUPEROXIDE-DISMUTASE IN ADRIAMYCIN NEPHROPATHY IN RATS

Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndr ome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric ac id) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin, Rats with nephrotic syndrome treated from th e beginning with cyclosporin had Lower proteinuria than untreated neph rotic rats, Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls, Act ivity of SOD in erythrocytes was significantly elevated in nephrotic r ats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythroc ytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10( 6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17. 49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduc ed proteinuria in rats with mild adriamycin nephropathy (similar to hu man minimal change disease). Cyclosporin also partially counteracted a driamycin-induced lipid peroxidation probably due to the stimulation o f antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves fu rther study.