Differential response of oxygen radical metabolism in rat heart, liver and kidney to cyclosporine A treatment.
OBJECTIVE
The study was designed to elucidate whether cyclosporine A (Cy A) induces oxidative stress in heart, liver and kidney.


METHODS
Male Wistar rats were treated with NaCl (n = 7), cremophor (vehicle for Cy A: n = 7) and 30 mg/kg b.w. Cy A in cremophor (n = 7) daily for 4 weeks.


METHODS
Oxidized (GSSG) and reduced (GSH) glutathione, lipid peroxides and superoxide dismutase were measured in the organs.


RESULTS
Increases in GSSG [nmol/mg prot.] and a compensatory rise in total GSH [nmol/mg prot.] indicating Cy A-induced oxidative stress were found in kidney (0.39 +/- 0.09 vs. 0.47 +/- 0.14 vs. 0.64 +/- 0.18; 20.71 +/- 3.86 vs. 21.07 +/- 3.86 vs. 28.14 +/- 3.37) and liver (0.51 +/- 0.11 vs. 0.51 +/- 0.09 vs. 0.65 +/- 0.25; 33.35 +/- 5.06 vs. 32.88 +/- 5.12 vs. 44.12 +/- 6.06) but not in heart.


CONCLUSIONS
Cy A-induced oxidative stress may contribute to the hepatotoxicity and nephrotoxicity of this drug. After heart transplantation, accelerated allograft atherosclerosis limits transplantation success. We did not find any evidence that Cy A induces oxidative stress in the heart which might favour atherogenesis.
Haberland
A
A
Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
Henke
W
W
Grune
T
T
Siems
W
W
Jung
K
K
Schimke
I
I
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis; D013481:Superoxides / Q000378:metabolism*
D007166:Immunosuppressive Agents; D013481:Superoxides; D016572:Cyclosporine; D013482:Superoxide Dismutase; D005978:Glutathione; D019803:Glutathione Disulfide