Venditti P, Pamplona R, Ayala V, De Rosa R, Caldarone G, Di Meo S
Dipartimento delle Scienze Biologiche, Sezione di Fisiologia, Università di Napoli, I-80134 Napoli, Italy.
J Exp Biol. 2006 Mar;209(Pt 5):817-25. doi: 10.1242/jeb.02045.
Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.
甲状腺激素诱导的代谢率增加通常与氧化应激增加有关。本研究的目的是,以冷暴露大鼠以及用3,5,3'-三碘甲状腺原氨酸(T3)或甲状腺素(T4)处理的大鼠为模型,研究在寒冷引起的功能性甲状腺功能亢进中,碘甲状腺原氨酸对肝脏氧化应激的影响。甲状腺功能亢进状态始终与组织的氧化能力和氧化损伤增加有关。脂质和蛋白质的最广泛损伤分别见于T3处理的大鼠和冷暴露的大鼠。线粒体和微粒体释放的氧反应性物质增加被发现会导致组织氧化损伤,而单一抗氧化剂的测定并未提供有关抗氧化防御系统有效性降低可能产生的影响的信息。实际上,甲状腺功能亢进大鼠的肝脏氧化损伤与脂溶性抗氧化剂的水平和抗氧化酶的活性几乎没有关系。相反,其他生化变化,如脂肪酸不饱和度和血红蛋白含量的程度,似乎使肝组织更容易受到甲状腺功能亢进状态引起的氧化应激相关的氧化损伤。总体而言,我们的结果证实了T3在冷应激肝脏中发现的代谢变化和氧化损伤中起关键作用这一观点。然而,只有关于谷胱甘肽过氧化物酶活性和线粒体蛋白质含量变化的数据支持以下观点,即冷暴露和T3处理效果的差异可能取决于血清T4水平的差异。