title: Antiarrhythmic effect of tamoxifen on the vulnerability induced by hyperthyroidism to heart ischemia/reperfusion damage.
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 3,5,3'-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.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico. Electronic address: echavez@salud.gob.mx.
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D045304:Cytochromes c / Q000378:metabolism; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006980:Hyperthyroidism / Q000150:complications*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D017392:Thiobarbituric Acid Reactive Substances; D013629:Tamoxifen; D045304:Cytochromes c
keywords: Heart damage; Hyperthyroidism; Ischemia/reperfusion; Mitochondria; Permeability transition; Tamoxifen