Dossier: Diabetes: Basic research and clinical approach. Part II Effect of a-tocopherol on the metabolic control and oxidative stress in female type 2 diabetics Jorge L. Ble-Castillo a,b,d, *, Elizabeth Carmona-Díaz b , José D. Méndez c , Francisco J. Larios-Medina d , Roberto Medina-Santillán d , Guadalupe Cleva-Villanueva d , Juan C. Díaz-Zagoya b,e a Hospital General de Zona No. 46, IMSS, Prolongación deAvenida Universidad Km 2.5, Colonia Casa Blanca, 86060 Villahermosa Tabasco, Mexico b Centro de Investigación DACS, UJAT, Villahermosa Tabasco, Mexico c Unidad de Investigación Médica en Enfermedades Metabólicas, Hospital de Especialidades, CMN Siglo XXI, IMSS, Mexico D.F., Mexico d Escuela Superior de Medicina, IPN, Mexico D.F., Mexico e Facultad de Medicina, UNAM, Mexico D.F., Mexico Received 22 February 2005 Available online 23 May 2005 Abstract In this study we evaluate the effects of a-tocopherol on the metabolic control and oxidative stress in female patients with type 2 diabetes mellitus. Thirty-four female type 2 diabetics 40–70 years old up to 14 years with diabetes, under medical treatment, were randomly divided in two groups. One group received placebo (Control group, n = 21) and the other received a-tocopherol (800 IU/day, n = 13) during 6 weeks. Blood samples were collected at the beginning and at the end of the study to measure malondialdehyde production, glycated hemoglobin, selenium dependent-glutathione peroxidase, Cu,Zn-superoxide dismutase in erythrocytes and total antioxidant status, glucose, lipid and lipo- proteins in serum. Erythrocyte malondialdehyde decreased and serum-total antioxidant status increased after a-tocopherol treatment (P < 0.0001). However, an unexpected increase on cholesterol levels and a reduced erythrocyte-Cu,Zn-superoxide dismutase activity was observed after a-tocopherol treatment. a-Tocopherol administration did not affect glucose, glycated hemoglobin, triacylglycerides, lipopro- tein levels and serum malondialdehyde. A minor oxidative stress was observed in female type 2 diabetic patients after a-tocopherol treatment inferred from the reduced levels of erythrocyte malondialdehyde and the increased values of total antioxidant status. On the other hand, no beneficial changes were observed on glycemic control or lipid metabolism. © 2005 Elsevier SAS. All rights reserved. Keywords: Diabetes mellitus; Vitamin E; Alpha-tocopherol; Oxidative stress; Antioxidant status; Lipoperoxidation 1. Introduction Type 2 diabetes is associated with increased oxidative stress, which probably results both from excess generation of reactive oxygen species and decreased antioxidant defenses [1,2]. In recent years, it has been known that, the most impor- tant factor to increase the free radicals production in diabetes is the hyperglycemic status, which can induce damage through overproduction of superoxide radical in the mitochondrion [3]. Superoxide is converted to hydroperoxyls, which can dif- fuse through membranes and initiate lipoperoxidation. The oxidation of unsaturated lipids has implications not only for atherosclerosis, but also for stability and integrity of the red cell membranes [4,5]. Increased levels of lipoperoxidation as evidenced by breakdown products like malondialdehyde, have been found in erythrocytes and plasma of type 2 diabetic patients [6–8]. Supplementation with antioxidants, is there- fore, an attractive potential therapy. It is known that a-tocopherol is a scavenger of superoxide and peroxyl radicals, and it is considered the most important inhibitor of lipoperoxidation, protecting polyunsaturated fatty acids from oxidation [9]. It has been reported that plasmatic a-tocopherol is lower in type 2 diabetic patients compared to * Corresponding aurhor. Tel.: +52 9931 16 0099; fax: +52 9933 54 3238. E-mail address: jblecastillo@cis.gob.mx (J.L. Ble-Castillo). Biomedicine & Pharmacotherapy 59 (2005) 290–295 http://france.elsevier.com/direct/BIOPHA/ 0753-3322/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.biopha.2005.05.002