Impacto da exposição á misturas químicas de desreguladores endócrinos desde a gestação até a idade adulta no coração de ratos Wistar

Abstract

Endocrine disruptors (ED) are substances that alter hormonal biosynthesis and promote toxic effects, causing cardiovascular diseases. However, the long-term effects of association of several ND on cardiac remodeling have been elucidated. The aim of this study was to evaluate the chronic effects of a DE mixture on cardiac remodeling in aspects related to structure, function and oxidative stress. Pregnant females of the Sprague-Dawley strain were divided into 2 experimental groups: CT Group (vehicle: corn oil, by gavage) and DE Mix Group: received 32.11mg/kg/day of a mixture consisting of twelve DE (phthalates, pesticides, u.v. filters, bisphenol A, butylparaben) diluted in corn oil (2ml/kg), by gavage. Pregnant or lactating rats received the treatment from gestational day 7 (DG7) until postnatal day 21 (DPN21). After weaning, at DPN22, the male offspring of the F1 generation continued to receive the DE mixture until they were 220 days old, after which they were euthanized. After this period, echocardiographic and histopathological analysis and analysis of oxidative stress were performed. There were no changes in the systolic (endocardial shortening: CT- 44.44 ± 3.12 % vs. DE Mix- 44.70 ± 3.32) and diastolic function of the left ventricle (E/A wave: CT- 3.37 ± 1.15 vs. DE Mix- 3.68 ± 1.20). It was possible to observe a significant decrease in the area of cardiomyocytes (CT- 347 ± 91.62 µm2 vs. DE Mix- 202 ± 72.70 µm2, p < 0.01) and there were no changes in the fractal dimension. Lipid peroxidation levels were reduced in the DE Mix Group (CT- 5.73 ± 0.36 vs. DE Mix- 5.17 ± 0.60 nmol/mg of protein, p = 0.008). The enzyme superoxide dismutase (SOD, CT- 10.18 ± 9.25 vs. DE Mix- 4.93 ± 1.48 U/ mg of protein, p= 0.10) and reduced Glutathione (GSH, CT- 28 .47 ± 15.17 vs. DE Mix- 39.66 ± 43.85 µM/mg protein, p= 0.53) did not change. There was a decrease in Glutathione -S- Transferase (GST, CT- 138.3 ± 28.44 vs. DE Mix- 113.8 ± 48.44, mM/mg of protein, p= 0.01). The chronic mixture of ED, since pregnancy, had a negative impact on the cardiac microenvironment, promoting cardiac atrophy and changes in oxidative stress markers, without promoting functional changes.