Molecular and Cellular Endocrinology 249 (2006) 133–139 Myocardial antioxidant enzyme activities and concentration and glutathione metabolism in experimental hyperthyroidism A.S.R. Araujo a , M.F.M. Ribeiro a , A. Enzveiler a , P. Schenkel a , T.R.G. Fernandes a , W.A. Partata a , M.C. Irigoyen a , S. Llesuy b , A. Bell ´ o-Klein a,∗ a Departamento Fisiologia, Instituto de Ciˆ encias B ´ asicas da Sa ´ ude, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil b C´ atedra de Qu´ ımica General e Inorgˆ anica, Facultad de Farm´ acia y Bioqu´ ımica, Universidad de Buenos Aires, Argentina Received 15 August 2005; received in revised form 9 February 2006; accepted 10 February 2006 Abstract Hyperthyroidism was induced in rats by l-thyroxine administration (12 mg/L in drinking water, 4 weeks). Animals were assessed hemody- namically, and heart, lung, and liver morphometry were performed. Lipid peroxidation (LPO) and protein oxidation (carbonyls) were measured in heart homogenates. It was quantified glutathione (GSH) metabolism, and antioxidant enzyme activities its and protein expression (by Western blot). At the end of treatment, it was observed cardiac hypertrophy, elevation of left ventricular systolic and end diastolic pressures, lung and liver congestion. LPO and carbonyls were increased in the hyperthyroid group, and GSH was decreased by 46% in the fourth week. Myocardial oxidative stress time course analysis revealed that it was increased in the second week of treatment. Antioxidant enzyme activities elevation was accompanied by protein expression induction in the hyperthyroid group in the fourth week. These results imply that hyperthyroidism generates myocardial dysfunction associated with oxidative stress inducing antioxidant enzyme activities and protein expression. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Hyperthyroidism; Lipid peroxidation; Antioxidant enzyme protein expression; Glutathione metabolism; Heart failure 1. Introduction Reactive oxygen species (ROS), generated as by-products of oxidative metabolism in mitochondria, can interact with biomolecules and damage various cellular components. Aer- obic organisms are endowed with antioxidant enzymes such as: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), catalase (CAT). As non-enzymatic defense molecules we can highlight reduced glutathione (GSH), ascorbate, vitamin E and flavonoids (Hogg and Kalyanamaran, 1999). However, when ROS generation exceeds the antioxidant capacity of cells, oxidative stress develops, potentially causing tissue damage (Esterbauer et al., 1991; Venditti et al., 1996). ROS have a high reactivity potential, therefore they are toxic and can lead to oxidative damage in cellular macromolecules such as proteins, lipids and DNA. Thus, ROS have been impli- ∗ Corresponding author at: Sarmento Leite, 500, CEP: 90050-170, Porto Ale- gre, RS, Brazil. Tel.: +55 2151 33163621; fax: +55 2151 33163166. E-mail address: belklein@ufrgs.br (A. Bell ´ o-Klein). cated in the pathophysiology of a large number of diseases. Evidence from experimental as well as clinical studies suggests the involvement of oxidative stress in the pathogenesis of cardiac dysfunction, such as heart failure (Singal and Iliskovic, 1998; Das and Chainy, 2001). Thyroid hormones are the most important factors involved in the regulation of the basal metabolic state, as well as in the oxidative metabolism (Asayama and Kato, 1990). Changes in thyroxine (T 4 ) and triiodothyronine (T 3 ) levels are the main events of physiological modulation of the mitochondrial res- piration process “in vivo”. Thyroid hormones can cause many changes in the number and activity of mitochondrial respiratory chain components. This may result in increased generation of ROS (Mano et al., 1995; Guerrero et al., 1999). Hyperthyroidism shows a hyperdynamic circulation, with increased cardiac output, increased heart rate, and decreased peripheral resistance. These cardiovascular manifestations of hyperthyroidism have been reproduced in rats under thyroid hor- mone treatment (Klein, 1990). The heart has a typically high aer- obic metabolic rate, with large and plentiful mitochondria. How- ever, the myocardial defense mechanism against oxygen toxicity is deficient and probably more susceptible to ROS attack. 0303-7207/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2006.02.005