title: Alpha-tocopherol and alpha-lipoic acid enhance the erythrocyte antioxidant defence in cyclosporine A-treated rats.
abstract: The aim of this study was to determine the effects of dietary antioxidant supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine A (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats were randomly assigned to either control, antioxidant (alpha-tocopherol 1000 IU/kg diet and alpha-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or cyclosporine + antioxidant treatments. Cyclosporine was administered for 7 days after an 8 week feeding period. Plasma was analysed for alpha-tocopherol, total antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Cyclosporine administration caused a significant decrease in superoxide dismutase activity (P<0.05 control versus cyclosporine) and this was improved by antioxidant supplementation (P<0.05 cyclosporine versus cyclosporine + antioxidant; P<0.05 control versus cyclosporine + antioxidant). Animals receiving cyclosporine and antioxidants showed significantly increased (P<0.05) catalase activity compared to both groups not receiving cyclosporine. Cyclosporine administration induced significant increases in plasma malondialdehyde and creatinine concentration (P<0.05 control versus cyclosporine). Antioxidant supplementation prevented the cyclosporine induced increase in plasma creatinine (P<0.05 cyclosporine versus cyclosporine + antioxidant; P>0.05 control versus cyclosporine + antioxidant), however, supplementation did not alter the cyclosporine induced increase in plasma malondialdehyde concentration (P>0.05 cyclosporine versus cyclosporine + antioxidant). Antioxidant supplementation resulted in significant increases (P<0.05) in plasma and erythrocyte alpha-tocopherol in both of the supplemented groups compared to non-supplemented groups. In conclusion, dietary supplementation with alpha-tocopherol and alpha-lipoic acid enhanced the erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine treated animals.
authors.affiliation: Physiology Laboratory, School of Community Health, Faculty of Health Studies, Charles Sturt University, Albury, 2640, Australia. llexis@csu.edu.au
authors.forename: Louise A
authors.initials: LA
authors.lastname: Lexis
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 / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D019587:Dietary Supplements; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D008063:Thioctic Acid; D016572:Cyclosporine; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol