Mukherjee Sutapa, Samanta Luna, Roy Anita, Bhanja Shravani, Chainy Gagan B N
Department of Zoology, Utkal University, Bhubaneswar, Odisha 751004, India ; Department of Zoology, Visva-Bharati (A Central University), Santiniketan, West Bengal 731235, India.
Department of Zoology, Utkal University, Bhubaneswar, Odisha 751004, India ; Department of Zoology, Ravenshaw University, Cuttack, Odisha 753003, India.
Biomed Res Int. 2014;2014:590897. doi: 10.1155/2014/590897. Epub 2014 May 28.
Hypothyroidism is a growing medical concern. There are conflicting reports regarding the mechanism of oxidative stress in hypothyroidism. Mitochondrial oxidative stress is pivotal to thyroid dysfunction. The present study aimed to delineate the effects of hepatic inner mitochondrial membrane dysfunction as a consequence of 6-n-propyl-2-thiouracil-induced hypothyroidism in rats. Increased oxidative stress predominance in the submitochondrial particles (SMP) and altered antioxidant defenses in the mitochondrial matrix fraction correlated with hepatocyte apoptosis. In order to check whether the effects caused by hypothyroidism are reversed by T3, the above parameters were evaluated in a subset of T3-treated hypothyroid rats. Complex I activity was inhibited in hypothyroid SMP, whereas T3 supplementation upregulated electron transport chain complexes. Higher mitochondrial H2O2 levels in hypothyroidism due to reduced matrix GPx activity culminated in severe oxidative damage to membrane lipids. SMP and matrix proteins were stabilised in hypothyroidism but exhibited increased carbonylation after T3 administration. Glutathione content was higher in both. Hepatocyte apoptosis was evident in hypothyroid liver sections; T3 administration, on the other hand, exerted antiapoptotic and proproliferative effects. Hence, thyroid hormone level critically regulates functional integrity of hepatic mitochondria; hypothyroidism injures mitochondrial membrane lipids leading to hepatocyte apoptosis, which is substantially recovered upon T3 supplementation.
甲状腺功能减退是一个日益受到关注的医学问题。关于甲状腺功能减退中氧化应激的机制，存在相互矛盾的报道。线粒体氧化应激是甲状腺功能障碍的关键因素。本研究旨在阐明6-正丙基-2-硫氧嘧啶诱导的大鼠甲状腺功能减退导致肝内线粒体膜功能障碍的影响。亚线粒体颗粒（SMP）中氧化应激优势增加以及线粒体基质部分抗氧化防御改变与肝细胞凋亡相关。为了检查甲状腺激素T3是否能逆转甲状腺功能减退所造成的影响，对一部分接受T3治疗的甲状腺功能减退大鼠的上述参数进行了评估。甲状腺功能减退的SMP中复合体I活性受到抑制，而补充T3可上调电子传递链复合体。由于基质谷胱甘肽过氧化物酶（GPx）活性降低，甲状腺功能减退时线粒体过氧化氢水平升高，最终导致膜脂质严重氧化损伤。甲状腺功能减退时SMP和基质蛋白稳定，但在给予T3后羰基化增加。两者中谷胱甘肽含量均较高。甲状腺功能减退的肝脏切片中可见明显的肝细胞凋亡；另一方面，给予T3具有抗凋亡和促增殖作用。因此，甲状腺激素水平严格调节肝线粒体的功能完整性；甲状腺功能减退会损伤线粒体膜脂质，导致肝细胞凋亡，补充T3后可基本恢复。
