title: Cyclosporine A-induced changes to erythrocyte redox balance is time course-dependent.
abstract: Cyclosporine A-treated transplant recipients develop pronounced cardiovascular disease and have increased oxidative stress and altered antioxidant capacity in erythrocytes and plasma. These experiments investigated the time-course of cyclosporine A-induced changes to redox balance in plasma and erythrocytes. Rats were randomly assigned to either a control or cyclosporine A-treated group. Treatment animals received 25 mg/kg of cyclosporine A via intraperitoneal injection for either 7 days or a single dose. Control rats were injected with the same volume of the vehicle. Three hours after the final injections, plasma was analysed for total antioxidant status, alpha-tocopherol, malondialdehyde, and creatinine. Erythrocytes were analysed for reduced glutathione (GSH), alpha-tocopherol, methaemoglobin, malondialdehyde, and the activities of superoxide dismutase, catalase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G6PD). Cyclosporine A administration for 7 days resulted in a significant increase (P<0.05) in plasma malondialdehyde, methaemoglobin, and superoxide dismutase and catalase activities. There was a significant decrease (P<0.05) in erythrocyte GSH concentration and G6PD activity in cyclosporine A animals. There were no significant differences (P>0.05) between groups following a single dose of cyclosporine A in any of the measures. In summary, cyclosporine A alters erythrocyte redox balance after 7 days administration, but not after a single dose.
authors.affiliation: Physiology Laboratory, School of Community Health, Charles Sturt University, Albury, 2640, Australia. llexis@csu.edu.au
authors.forename: Louise A
authors.initials: LA
authors.lastname: Lexis
authors.forename: Ross S
authors.initials: RS
authors.lastname: Richards
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fassett
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008706:Methemoglobin / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000975:Antioxidants; D006454:Hemoglobins; D007166:Immunosuppressive Agents; D008315:Malondialdehyde; D016572:Cyclosporine; D008706:Methemoglobin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase