Efeito do açaí juçara no desenvolvimento tumoral: análise no número de focos de criptas aberrantes, lesões e da expressão de Sod1, Gpx e Ogg1 em modelo experimental de carcinogênese colorretal

Abstract

The Acai Juçara (Euterpe edulis Martius) is a native palm tree from the Atlantic Forest, which belongs to the Arecaceae family. It produces small fruits that have high energy value and considerable levels of antioxidant compounds, such as anthocyanins. Colorectal cancer is a “lifestyle” disease, so an antioxidant-rich diet helps prevent it by activating cytoprotection pathways and the antioxidant cell response by inducing transcription of various genes. Thus, the objective of this project was to evaluate the effect of Juçara supplementation, in the form of lyophilized juice and extract, on the tumor development process by counting aberrant crypt foci (FCA) and analyzing the expression of SOD1, GPx and OGG1, oxidative stress pathways and DNA repair in rats induced by colorectal carcinogenesis. For this, 38 Wistar rats were used, 10 with healthy bowel as negative control DMH- /Juçara- and the remaining 28 were induced by 1,2dimethylhydrazine (DMH) colorectal tumorigenesis and divided into 3 groups: carcinogenesis-induced group (DMH+/Juçara-), containing 12 animals, group supplemented with Juçara juice (DMH+/Juçara+), with 10 animals, group supplemented with Juçara extract (DMH+/Extract), containing 6 animals. Supplementation with juice and lyophilized extract occurred three times a week by gavage until the 23 weeks. At week 10, four animals from the DMH-/Juçara-, DMH+/Juçara- and DMH+/Juçara+ groups and two animals from the DMH+/Extract group were euthanized for analysis of pre-neoplastic lesions. And at week 23 the remaining animals from all groups were euthanized for removal of lesions larger than 0.1 cm, which were fixed, histologically processed and stained with Hematoxylin-eosin for diagnosis. Lesions classified as tubular adenocarcinoma were submitted to immunohistochemistry for proteins SOD1, GPx and OGG1. The DMH+/Juçara+ group showed a significant reduction (p=0.0054) in the total number of ACF in the colorectal mucosa of rats induced by carcinogenesis, when compared to the DMH+/Juçara- group. Similarly, analysis considering foci equal to or less than 3 crypts (p=0.0381) and greater than 3 crypts (p=0.0024) also showed a reduction in the number of ACF from the DMH+/Juçara+ group when compared to the DMH+/Juçara- group. Regarding the analysis of the expression of oxidative stress enzymes, the DMH+/Extract group showed lower SOD1 expression compared to the DMH+/Juçara group in the intratumoral inflammatory infiltrate (p=0.012) and in the tumor cells (p=0.022). In addition, the DMH+/Juçara+ group showed significantly higher GPx expression (p<0.019) ) than that shown in the DMH+/Juçara group in the cells of the intratumoral inflammatory infiltrate. On the other hand, there was no significant difference between the expression of OGG1 in both intratumoral inflammatory infiltrate and tumor cells (p=0.102). It was observed in this experiment that acai Juçara may be an ally in the prevention of the early stages of colorectal cancer, given the reduction in the number of ACF in the colon epithelium and that reactive oxygen species generated after DMH administration were effectively