Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8338793 | The Journal of Steroid Biochemistry and Molecular Biology | 2014 | 8 Pages |
Abstract
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 3,5,3â²-triiodothyronine at 2Â mg/kg body weight during 5 days to induce hyperthyroidism. One group was treated with 10Â mg/kg tamoxifen and another was not. The protective effect of the drug on heart rhythm was analyzed after 5Â min of coronary occlusion followed by 5Â 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 Ca2+ 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.
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Authors
Natalia Pavón, Luz Hernández-Esquivel, Mabel Buelna-Chontal, Edmundo Chávez,