Efeito da radiação ionizante e quimioterapicos em tecido cardíaco e expressão do peptídeo natriurético do tipo B

Abstract

The use of specific cardiac biomarkers has been recommended as a useful tool in the early identification and monitoring of cardiac injury, due to the potential cardiotoxicity of oncological therapy. The aim of this study is to investigate, analyze and evaluate the reaction of B-type natriuretic peptide (BNP), interleukin-6 (IL-6), transforming growth factor β1 (TGF-β1) and procollagen type I in its expression and release by the association of antineoplastic agents Docetaxel and Cyclophosphamide (TC) and ionizing radiation (IR) in the heart of Wistar rats, 2 months after the end of treatment. For this, Wistar rats (3-4 months, n = 7) were irradiated in the heart with a single dose of 20 Gy, in a anteroposterior field of 2x2cm2 in linear accelerator with nominal energy beam of 6 MeV, other (n = 7) were treated (four cycles with a 7-day interval) with docetaxel (12.5 mg / kg) and Cyclophosphamide (50 mg / kg) and irradiated after 7 days of chemotherapy. As a control (n = 7), non-irradiated animals not treated with chemotherapy. 2 months after the end of treatment, euthanasia was performed. Samples of plasma and heart tissue, left ventricular (LV) were collected. The plasma concentration of BNP was quantified by ELISA, part of the heart tissue was fixed, embedded in paraffin and cut in microtome, to signal the presence of BNP in the LV, qualitative evaluation by immunohistochemistry (IHC), and the other party to technique RT-qPCR were evaluated in the relative expression of mRNA of the genes of BNP, ANP, IL-6, TGF-β1 and procollagen type I. In the control group IHC showed a marking point, while the treated groups showed a more diffuse labeling, and the CT + RT group showed the greatest dispersion. Although it was not observed in the ELISA assay a significant difference between plasma concentrations of BNP treated groups compared to control, there is an increasing trend in the CT + RT group. In the analysis by RT-qPCR, the relative expression of BNP was similar to that shown in the ELISA. The CT + RT group was the group that showed higher gene expression of BNP, but the difference is not significant compared to control. The only analysis that which obtained difference in gene expression compared to control was the IL-6 gene that showed low expression. All other genes analyzed by RT-qPCR showed an expression similar to control. Therefore, the outcome is that BNP did not appear as a good specific cardiac biomarker for early identification of cardiac disease, within 2 months after treatment in Wistar rats, by effect of the action of cardiotoxic selected treatment protocols, since none of their quantitative assessments showed a differentiated result compared to control, however, there was no evidence that, in the meantime, there would be a scenario in development, or advanced of cardiac remodeling.