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This Article Full Text Full Text (PDF) All Versions of this Article: JME-08-0024v1 41/6/423    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Araujo, A S R Articles by Belló-Klein, A Search for Related Content PubMed PubMed Citation Articles by Araujo, A S R Articles by Belló-Klein, A

Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, CEP 90050-170 Porto Alegre, RS, Brazil¹ Cátedra de Química General y Inorgánica, Facultad de Farmácia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina² Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada³ Faculty of Medicine, St Boniface Hospital Research Centre, University of Manitoba, 351 Tache Avenue, Winnipeg, Manitoba, Canada R2H 2A6

(Correspondence should be addressed to A Belló-Klein; Email: belklein{at}ufrgs.br)

This study was conducted to test whether oxidative stress activates the intracellular protein kinase B (AKT1) signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T₄), and T₄+vitamin E. Hyperthyroidism was induced by T₄ administration (12 mg/l in drinking water for 28 days). Vitamin E treatment was given during the same period via s.c. injections (20 mg/kg per day). Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H₂O₂), and nitric oxide metabolites (NO_X) were measured in heart homogenates. The p-AKT1/AKT1 ratio, p-glycogen-synthase kinase (GSK)3B/GSK3B ratio, FOS, and JUN myocardial protein expression were also quantified by western blot after 4 weeks. Increases in biochemical parameters, such as protein oxidation (41%), H₂O₂ (62%), and NO_X (218%), and increase in the left ventricular end-diastolic pressure were observed in the T₄ group. T₄ treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-AKT1/AKT1, p-GSK3B/GSK3B, FOS, and JUN were elevated in the T₄ group (by 69, 37, 130, and 33% respectively), whereas vitamin E administration promoted a significant reduction in their expression. These results indicate that oxidative stress plays an important role in cardiac hypertrophy, and suggest redox activation of AKT1 and JUN/FOS signaling pathways with H₂O₂ acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.