Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction.
The aim of this study was to determine the effects of dietary antioxidant supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine-induced alterations to erythrocyte and plasma redox balance, and cyclosporine-induced endothelial and smooth muscle dysfunction. Rats were randomly assigned to either control, antioxidant, cyclosporine or cyclosporine + antioxidant treatments. Cyclosporine A was administered for 10 days after an 8-week feeding period. Plasma was analyzed for alpha-tocopherol, total antioxidant capacity, malondialdehyde and creatinine. Erythrocytes were analyzed for glutathione, methemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Vascular endothelial and smooth muscle function was determined in vitro. Antioxidant supplementation resulted in significant increases in erythrocyte alpha-tocopherol concentration and glutathione peroxidase activity in both of the antioxidant-supplemented groups. Cyclosporine administration caused significant decreases in glutathione concentration, methemoglobin concentration and superoxide dismutase activity. Antioxidant supplementation attenuated the cyclosporine-induced decrease in superoxide dismutase activity. Cyclosporine therapy impaired both endothelium-independent and -dependent relaxation of the thoracic aorta, and this was attenuated by antioxidant supplementation. In summary, dietary supplementation with alpha-tocopherol and alpha-lipoic acid attenuated the cyclosporine-induced decrease in erythrocyte superoxide dismutase activity and attenuated cyclosporine-induced vascular dysfunction.
Lexis
L A
LA
Physiology Laboratory, School of Community Health, Charles Sturt University, Albury, Australia. llexis@csu.edu.au
Fenning
A
A
Brown
L
L
Fassett
R G
RG
Coombes
J S
JS
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D019587:Dietary Supplements; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects*; D005978:Glutathione / Q000097:blood; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008706:Methemoglobin / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000097:blood; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000097:blood; D014652:Vascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000097:blood
D000975:Antioxidants; D007166:Immunosuppressive Agents; D013481:Superoxides; D008315:Malondialdehyde; D008063:Thioctic Acid; D016572:Cyclosporine; D008706:Methemoglobin; D003404:Creatinine; D005978:Glutathione; D024502:alpha-Tocopherol