Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina

Abstract

Cardiotoxicity is one of the most significant adverse effects of oncologic treatment with doxorubicin being responsible for a high morbidity and mortality rate. These effects include the occurrence of cardiotoxicity that can lead to left ventricular dysfunction, heart failure and, ultimately, death. Studies have focused on the effects of leucine supplementation as a strategy to ameliorate and / or reverse the framework of proteolysis induced by various clinical complications. However, the impact of leucine supplementation on cardiotoxicity induced by doxorubicin is unknown. Objective: The objective of this study was to evaluate the effects of leucine supplementation on cardiotoxicity in rats treated with doxorubicin. Material and Methods: The experiment was carried out at the Center for Bioterism and Animal Experimentation (CEBEA-UFU) and lasted 42 days. Thirty-six male Wistar rats weighing between 250 and 300 grams were randomly assigned to four groups: Control (8 animals), Doxorubicin (10 animals), Leucine (8 animals) and Leucine + Doxorubicin (10 animals). Groups C and D received standard diet, while L and LD groups received leucine rich diet (supplemented in 5%). The animals of groups D and LD received intraperitoneal injections of doxorubicin three times a week over two weeks, reaching a cumulative dose of 7.5 mg / kg. Groups C and L received saline solution (NaCl 0.9%), intraperitoneally, in the same volume used for animals treated with doxorubicin. At the end of the experiment the animals were anesthetized and submitted to transthoracic echocardiography. At the end of experimental period cardiac collagen was quantified by histopathological study. For the comparisons between the groups, Student's t-Test or analysis of variance (ANOVA) was used, followed, by Tukey's test when necessary. Statistical significance was set at p <0.05. Results: In rats treated with a cumulative dose of 7.5 mg / kg doxorubicin, left ventricular (LV) dilation and decreased ejection fraction (LVEF) occurred. Leucine supplemented at 5% in the diet, prevented dilation and LV dysfunction when coadministered with doxorubicin. Changes in extracellular matrix remodeling were confirmed by the increase in collagen fibers in group D, which was attenuated when leucine supplementation occurred. There was a significant difference in the transverse diameter of the cardiomyocytes when the L, D and LD groups were compared with the C group, with the lower diameters found in the C group. Conclusion: Leucine attenuates cardiotoxicity in the experimental model of Wistar rats treated with doxorubicin and this effect is accompanied by maintenance of the collagen matrix.