The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats.
Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, 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 acid) 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 the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, 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 reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.
Zima
T
T
First Institute of Medical Chemistry and Biochemistry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Tesar
V
V
Stípek
S
S
Crkovská
J
J
Poledne
R
R
Tĕmínová
J
J
Pláteník
J
J
Rychlík
I
I
Merta
M
M
Nĕmecek
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic; D003524:Cyclosporins / Q000494:pharmacology*; D004317:Doxorubicin; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000097:blood; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D004317:Doxorubicin; D013482:Superoxide Dismutase