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 μg · 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.SCOPUS: ar.j