Efeitos cardiovasculares da associação do hormônio tireoidiano e do treinamento físico na cardiotoxicidade induzida por doxorrubicina em ratos

Abstract

Introduction: Doxurrubicin (DOX is a chemotherapeutic agent that, in addition to its antineoplastic properties, can also cause toxic effects on the heart with consequent heart failure Thyroid hormones play an important role in the growth, development, and metabolism of the body. A target for the action of these hormones is cardiac tissue where they exert a large number of influences promoting structural, functional and molecular changes. Another approach that brings benefits to the treatment of HF is physical exercise, which causes innumerable morphofunctional adaptations that occur at both the central and peripheral levels. There are, to the best of our knowledge, no studies concerning the use of the physical exercise after the use of DOX and the possibility of using thyroid hormone in this clinical situation. Objective: This study aimed to analyze the effects of thyroid hormone and physical training on DOX-induced cardiotoxicity by assessing the tolerance response to physical effort, structural changes in the myocardium and cardiac function. Materials and methods: Sixty male Wistar rats were randomly alocated to seven groups: control (C), exercise (EX), thyroid hormone (TH), doxorubicin (DX), doxorubicin and exercise (DXEX), doxorubicin and hormone (DXTH) and doxorubicin + exercise and hormone (DXEXTH). The animals from DX, DXEX, DXTH e DXEXTH groups received intraperitoneal injections of doxorubicin hydrocloride, three times a week, for two weeks, reaching a cumulative dose of 7.5mg/kg. After two weeks of the ending the infusion of DOX, the groups TH, DXTH and DXEXTH began to receive daily thyroid hormone, for four weeks, by orogastric probe, at a dose of 10μg/100g of body weight. Also, after two weeks of DOX administration, the groups EX, DXEX e DXEXTH performed exercise using swimming for four weeks with three weekly sessions. The exercised was performed using a loading up to 5% of body weight. The training was conducted during 4 weeks with three weekly swimming sessions. Forty-eight hours after the last training session, animals from all groups underwent a thorough swimming test, which consisted of swimming to exhaustion, with an overload of 5% of body weight fixed to the body. After the tolerance test, echocardiography was performed and fragments of left ventricle was obtained and processed to conventional light microscopy. Tolerance test, heart rate, ejection fraction and shortening fraction values were compared between the categories with Generalized Linear Models, with a significance of 5%. Results: The exercise tolerance (ET) in the EX group was higher when compared to the other experimental groups. The DXEX group presented better ET when compared to the DX group. Thyroid hormone given after DOX increased ET but less effectively than exercise. The exercise protocol used after the use of DOX increased ET and the association with thyroid hormone did not potentiate this effect. The association also did not worsen the physical performance of the animals. Increased myocardial cells were observed in size without infiltrating inflammatory cells in the DXEX group. The behavior of the ejection fraction of the DX group presented lower value in comparison to group C, EX and DXEX. Conclusion: We concluded that training with regular and low intensity exercise and thyroid hormone after use of DOX improved the effort tolerance of the animals and preserved the cardiac structure and function of rats after DOX treatment.