Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats: effect of vitamin E on cyclosporine nephrotoxicity.
BACKGROUND
We report an investigation of the effects of cyclosporine (CsA) on kidney function, the glomerular synthesis of reactive oxygen species, the peroxidation of lipids, and the levels of thromboxane B2 (TXB2). The effect of the simultaneous administration of the antioxidant vitamin E (Vit E) and CsA in rats was also evaluated.


METHODS
Adult male Wistar rats were treated for 30 days with CsA (30 mg/kg/day), with Vit E (0.05 mg/ml), with CsA plus Vit E, or with the vehicle used for administration of CsA, namely 12.6% ethanol.


RESULTS
CsA induced kidney failure and increased the glomerular synthesis of superoxide anion, H2O2, malonyldialdehyde, and TXB2. Vit E minimized the adverse effects of CsA on kidney function and the glomerular synthesis of these compounds.


CONCLUSIONS
Our results suggest that the acute decrease in glomerular filtration rate induced by CsA might be mediated by the synthesis of reactive oxygen species and subsequent peroxidation of lipids, which increases the levels of TXB2. Treatment with Vit E prevented these effects, suggesting a possible role for antioxidants in the prevention of CsA nephrotoxicity.
Parra
T
T
Research Unit, Hospital General Universitario de Guadalajara, Spain.
de Arriba
G
G
Conejo
J R
JR
Cantero
M
M
Arribas
I
I
Rodríguez-Puyol
D
D
Rodríguez-Puyol
M
M
Carballo
F
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced; D007678:Kidney Glomerulus / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D008315:Malondialdehyde; D016572:Cyclosporine