Prevention by selenium supplementation of cyclosporin-A-induced vascular toxicity.
OBJECTIVE
The aim was to determine whether selenium supplementation, an important component of glutathione peroxidase, might attenuate cyclosporin (Cx)-induced vascular toxicity.


METHODS
Four groups of rats were treated in parallel: the first group was supplemented with selenium (sodium selenite, 0.5 mg.kg-1) orally (p.o.) for 5 weeks and the same dose of selenium plus Cx 20 mg.kg-1 (i.m.) during the 6th week; group 2 received Cx only (20 mg.kg-1 i.m. for 1 week); group 3 was supplemented with selenium (0.5 mg.kg-1 p.o., for 6 weeks) and group 4 served as control. Thoracic aortas isolated from these various groups were studied in organ baths.


RESULTS
In comparison with the control group, selenium supplementation did not modify acetylcholine (Ach)- and nitroprusside-induced relaxations. In group 2, endothelium-dependent relaxations (Ach) were markedly impaired and endothelium-independent relaxations (nitroprusside) were shifted to the right; with selenium supplementation (group 1), the responses to Ach were partially restored whereas the rightward shift of the concentration-response curves to nitroprusside persisted. Incubation with superoxide dismutase (SOD, 150 IU.ml-1) or selenium (1 microgram.ml-1) (but not with selenium plus an inhibitor of the glutathione redox cycle) improved the relaxations to Ach in group 2.


CONCLUSIONS
The vascular toxicity of Cx seems related to generation of oxygen-derived radicals promoting EDRF destruction and is attenuated by selenium supplementation.
Berkenboom
G
G
Cardiology Department, Erasmus Hospital, Brussels, Belgium.
Brékine
D
D
Fang
Z Y
ZY
Nève
J
J
Fontaine
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001011:Aorta; D016572:Cyclosporine / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008297:Male; D008954:Models, Biological; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D009599:Nitroprusside; D016572:Cyclosporine; D013482:Superoxide Dismutase; D012643:Selenium; D000109:Acetylcholine