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First published online March 12, 2009
Journal of Experimental Biology 212, 986-993 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.021808

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T₃ and the thyroid hormone β-receptor agonist GC-1 differentially affect metabolic capacity and oxidative damage in rat tissues

P. Venditti^1,*, G. Chiellini², A. Bari¹, L. Di Stefano¹, R. Zucchi², A. Columbano³, T. S. Scanlan⁴ and S. Di Meo¹

¹ Dipartimento delle Scienze Biologiche, Sezione di Fisiologia, Università di Napoli, 80134 Napoli, Italy
² Dipartimento di Scienze dell'Uomo e dell'Ambiente (G.C.), University of Pisa, Pisa 56126, Italy
³ Department of Toxicology, Oncology, and Molecular Pathology Unit, University of Cagliari, 09124 Cagliari, Italy
⁴ Department of Physiology and Pharmacology and Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA

^* Author for correspondence (e-mail: venditti{at}unina.it)

Accepted 6 January 2009

We compared the changes in tissue aerobic metabolism and oxidative damage elicited by hypothyroid rat treatment with T₃ and its analog GC-1. Aerobic capacities, evaluated by cytochrome oxidase activities, were increased more by T₃ than by GC-1. Furthermore, the response of the tissues to T₃ was similar, whereas the response to GC-1 was high in liver, low in muscle and scarce in heart. Both treatments induced increases in ADP-stimulated O₂ consumption, which were consistent with those in aerobic capacities. However, unlike T₃, GC-1 differentially affected pyruvate/malate- and succinate-supported respiration, suggesting that respiratory chain components do not respond as a unit to GC-1 stimulation. According to the positive relationship between electron carrier levels and rates of mitochondrial generation of oxidative species, the most extensive damage to lipids and proteins was found in T₃-treated rats. Examination of antioxidant enzyme activities and scavenger levels did not clarify whether oxidative damage extent also depended on different antioxidant system effectiveness. Conversely, the analysis of parameters determining tissue susceptibility to oxidants showed that pro-oxidant capacity was lower in GC-1- than in T₃-treated rats, while antioxidant capacity was similar in treatment groups. Interestingly, both agonists decreased serum cholesterol levels, but only GC-1 restored euthyroid values of heart rate and indices of tissue oxidative damage, indicating that GC-1 is able to lower cholesterolemia, bypassing detrimental effects of T₃.

Key words: thyroid hormone, thyroid hormone agonist, oxidative metabolism, oxidative damage

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