Fidale Thiago M, Antunes Hanna K M, Alex Dos Santos Luciano, Rodrigues de Souza Fernanda, Deconte Simone R, Borges Rosa de Moura Francyelle, Mantovani Matheus M, Alves Duarte Poliana Rodrigues, Roever Leonardo, Resende Elmiro S
Laboratory of Experimental Medicine, Federal University of Uberlândia, Uberlândia, Brazil.
Department of Bioscience, Federal University of São Paulo, São Paulo, Brazil.
Front Physiol. 2018 Jan 17;8:1042. doi: 10.3389/fphys.2017.01042. eCollection 2017.
Cardiotoxicity is one of the most significant adverse effects of the oncologic treatment with doxorubicin, which is responsible for a substantial morbid and mortality. The occurrence of heart failure with ventricular dysfunction may lead to severe cardiomyopathy and ultimately to death. Studies have focused on the effects of leucine supplementation as a strategy to minimize or revert the clinical condition of induced proteolysis by several clinical onsets. However, the impact of leucine supplementation in heart failure induced by doxorubicin is unknown. Therefore, the objective of this work is to evaluate the effects of leucine supplementation on the cardiotoxicity in the heart of rats treated with doxorubicin. Rats treated with a 7.5 mg/kg cumulative dose of doxorubicin for 14 days presented a dilatation of the left ventricle (LV), and a reduction of the ejection fraction (FE). The 5% supplementation of leucine in the rats' food prevented the malfunctioning of the LV when administered with doxorubicin. Some alterations in the extracellular matrix remodeling were confirmed by the increase of collagen fibers in the doxorubicin group, which did not increase when the treatment was associated with leucine supplementation. Leucine attenuates heart failure in this experimental model with doxorubicin. Such protection is followed by the maintenance of interstitial collagen fibers.
心脏毒性是阿霉素肿瘤治疗最显著的不良反应之一，它会导致大量的发病和死亡。伴有心室功能障碍的心力衰竭的发生可能会导致严重的心肌病并最终导致死亡。研究集中于补充亮氨酸的作用，将其作为一种策略以最小化或逆转由多种临床发作引起的蛋白水解的临床状况。然而，补充亮氨酸对阿霉素诱导的心力衰竭的影响尚不清楚。因此，这项工作的目的是评估补充亮氨酸对用阿霉素治疗的大鼠心脏毒性的影响。用7.5mg/kg累积剂量的阿霉素治疗14天的大鼠出现左心室扩张和射血分数降低。当与阿霉素一起给药时，在大鼠食物中补充5%的亮氨酸可防止左心室功能失调。阿霉素组胶原纤维增加证实了细胞外基质重塑的一些改变，当治疗与补充亮氨酸相关联时，这种增加并未出现。在这个阿霉素实验模型中，亮氨酸可减轻心力衰竭。这种保护作用伴随着间质胶原纤维的维持。
