title: Cyclosporine A induced changes to plasma and erythrocyte antioxidant defences.
abstract: Organ transplant recipients develop pronounced cardiovascular disease, and decreased antioxidant capacity in plasma and erythrocytes is associated with the pathogenesis of this disease. These experiments tested the hypothesis that the immunosuppressant cyclosporine A (CsA) alters erythrocyte redox balance and reduces plasma antioxidant capacity. Female Sprague-Dawley rats were randomly assigned to a control or CsA treated group. Treatment animals received 25 mg/kg/day of CsA via intraperitoneal injection for 18 days. Control rats were injected with the same volume of the vehicle. Three hours after the final CsA injection, rats were exsanguinated and plasma analysed for total antioxidant status (TAS), alpha-tocopherol, malondialdehyde (MDA), and creatinine. Erythrocytes were analysed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glucose-6-phosphate dehydrogenase (G6PD) activities, alpha-tocopherol, and MDA. CsA administration resulted in a significant (P < 0.05) decrease in plasma TAS and significant increases (P < 0.05) in plasma creatinine and MDA. Erythrocyte CAT was significantly (P < 0.05) increased in CsA treated rats compared to controls. There were no significant differences (P > 0.05) in erythrocyte SOD, GPX, G6PD, alpha-tocopherol or MDA between groups. In summary, CsA alters erythrocyte antioxidant defence and decreases plasma total antioxidant capacity.
authors.affiliation: Physiology Laboratory, School of Community Health, Charles Sturt University, Albury, Australia. lfletcher@csu.edu.au
authors.forename: Louise A
authors.initials: LA
authors.lastname: Fletcher
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fassett
authors.forename: Ross S
authors.initials: RS
authors.lastname: Richards
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008315:Malondialdehyde / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D016572:Cyclosporine; D003404:Creatinine