Pavón Natalia, Hernández-Esquivel Luz, Buelna-Chontal Mabel, Chávez Edmundo
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
J Steroid Biochem Mol Biol. 2014 Sep;143:416-23. doi: 10.1016/j.jsbmb.2014.06.006. Epub 2014 Jun 9.
Hyperthyroidism, known to have deleterious effects on heart function, and is associated with an enhanced metabolic state, implying an increased production of reactive oxygen species. Tamoxifen is a selective antagonist of estrogen receptors. These receptors make the hyperthyroid heart more susceptible to ischemia/reperfusion. Tamoxifen is also well-known as an antioxidant. The aim of the present study was to explore the possible protective effect of tamoxifen on heart function in hyperthyroid rats. Rats were injected daily with 3,5,3'-triiodothyronine at 2mg/kg body weight during 5 days to induce hyperthyroidism. One group was treated with 10mg/kg tamoxifen and another was not. The protective effect of the drug on heart rhythm was analyzed after 5 min of coronary occlusion followed by 5 min reperfusion. In hyperthyroid rats not treated with tamoxifen, ECG tracings showed post-reperfusion arrhythmias, and heart mitochondria isolated from the ventricular free wall lost the ability to accumulate and retain matrix Ca(2+) and to form a high electric gradient. Both of these adverse effects were avoided with tamoxifen treatment. Hyperthyroidism-induced oxidative stress caused inhibition of cis-aconitase and disruption of mitochondrial DNA, effects which were also avoided by tamoxifen treatment. The current results support the idea that tamoxifen inhibits the hypersensitivity of hyperthyroid rat myocardium to reperfusion damage, probably because its antioxidant activity inhibits the mitochondrial permeability transition.
甲状腺功能亢进已知对心脏功能有有害影响，且与代谢状态增强有关，这意味着活性氧的产生增加。他莫昔芬是雌激素受体的选择性拮抗剂。这些受体使甲状腺功能亢进的心脏对缺血/再灌注更敏感。他莫昔芬也是一种著名的抗氧化剂。本研究的目的是探讨他莫昔芬对甲状腺功能亢进大鼠心脏功能的可能保护作用。大鼠连续5天每天以2mg/kg体重注射3,5,3'-三碘甲状腺原氨酸以诱导甲状腺功能亢进。一组用10mg/kg他莫昔芬治疗，另一组不治疗。在冠状动脉闭塞5分钟后再灌注5分钟，分析该药物对心律的保护作用。在未用他莫昔芬治疗的甲状腺功能亢进大鼠中，心电图显示再灌注后心律失常，从心室游离壁分离的心脏线粒体失去了积累和保留基质Ca(2+)以及形成高电位梯度的能力。这两种不良反应在他莫昔芬治疗后均得以避免。甲状腺功能亢进诱导的氧化应激导致顺乌头酸酶抑制和线粒体DNA破坏，这些作用在他莫昔芬治疗后也得以避免。目前的结果支持这样一种观点，即他莫昔芬抑制甲状腺功能亢进大鼠心肌对再灌注损伤的超敏反应，可能是因为其抗氧化活性抑制了线粒体通透性转换。
