Quimioprevenção de lesões precursoras do câncer colorretal após suplementação de pterostilbene e probiótico em modelo experimental de carcinogênese intestinal, com 1,2-dimetil-hidrazina

Abstract

Introduction:Introduction. Food is the environmental factor most related to the development of non-hereditary Colorectal Cancer (CRC). The composition of the intestinal microbiota, prolonged intestinal inflammation and oxidative stress are factors related to the appearance of CRC. Pteriostilbene (PS) has antioxidant, anti-inflammatory and antitumor action. Probiotic (PRO) supplementation with Lactobacillus and Bifidobacterium is beneficial for intestinal health. The role of the microbiota in PS metabolization should be explored and the combination of substances can potentiate CRC chemoprevention.Objective:To evaluate the effect of PS and/or PRO supplementation on the development of CRC precursor lesions in wistar rats after CRC induction with 1,2-DMH.Methods:Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO and 1,2-DMH + PS + PRO. PRO (5 × 107 / mL) was offered in water and PS (300 ppm) in the ad libitum diet. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. At the 25th week, a proctocolectomy was performed. Half of the samples were used to evaluate histopathological scores (inflammation score, aberrant foci of crypts, macroscopic lesions) and expression of Ki67, β-catenin, Wnt3a, p53, NF-kB, iNOS, IL1-β and TNF-α proteins. In the other half, oxidative stress (OS) was evaluated through levels of GSH and MDA. Statistical analysis was performed using GraphPad Prism software. Parametric data were evaluated by One-Way ANOVA test of variance followed by Tukey's multiple comparisons test and non-parametric data were analyzed by Kruskal-Wallis test followed by Dunns' multiple comparisons test. The significance level adopted was 0.05. Results:1,2-DMH increases histopathological scores, protein expression and OS relative to SHAM (p<0.05). 1,2-DMH + PRO and 1,2-DMH + PS + PRO reduce histopathological scores, protein expression (Ki67, β-catenin, Wnt3a, p53, NF-kB, iNOS, IL1-β and TNF-α) and OS (MDA) (p<0.05). 1,2-DMH + PS + PRO also increases GSH levels (p<0.05). 1,2-DMH + PS reduces p53, Ki67, IL1-β and TNF-α protein expression (p<0.05), but without improvement in histopathological scores and OS. Conclusions:PRO and PS + PRO supplementation are the best intervention strategies to attenuate several parameters of intestinal carcinogenesis and CRC precursor lesions.