EFFECTS OF JABOTICABA PEEL SUPPLEMENTATION ON CHRONIC COLITIS-ASSOCIATED COLORECTAL CANCER

Inflammatory bowel diseases are immune-mediated disorders that can promote considerable injury to the colon. Over time, such alterations may contribute to carcinogenesis, potentially leading to adenocarcinoma formation. Polyphenols and fibers are often referred to as preventive interventions against chronic illnesses, given their antioxidant and anti-inflammatory effects. Therefore, the objective of the study was to understand the preventive effects of jaboticaba peel, a promising functional food, on mice with colitis-associated colorectal cancer. Plinia jaboticaba peel was freeze-dried, powdered, and analyzed for its content in fibers, total phenolic compounds by Folin-Ciocalteu, and specific polyphenols by high-performance liquid chromatography. Jaboticaba peel was added to the diet of male Balb/c mice at 0, 2.5, or 5% concentrations. On day 28, mice received an injection of the carcinogenic azoxymethane. One week after, dextran sodium sulfate was added to the drinking water for seven days and two cycles. During the experiment, mice were scored for weight loss, stool consistency, and bleeding. The experiment ended on day 119. On euthanasia, the colon was collected, and tumors were counted. The distal colon was processed and analyzed histologically. The colonic concentrations of interleukin-1beta and tumor necrosis factor-alpha were analyzed by enzyme-linked immunosorbent assay, while the expressions of cyclooxygenase-2 and phosphorylated nuclear factor-kappa B p65, by Western Blotting. Jaboticaba peel showed 35.77 ± 0.12% of total dietary fibers, 8.43 ± 0.13% of total phenolic compounds, 1.45 ± 0.23% of cyanidin-3-O-glucoside, 0.12 ± 0.003 of delphinidin-3-O-glucoside, 0.29 ± 0.007% of ellagic acid, and 0.32 ± 0.01% of gallic acid. When compared to the control group, the cancer group showed episodes of diarrhea and bleeding (p<0.05). The cancer group showed around 11 visible points of tumor, with 83% of animals presenting adenoma or adenocarcinoma by microscopy, besides damaged epithelium tissue (p<0.05). The disease model increased the expressions of cyclooxygenase-2 and nuclear factor kappa B (p<0.05), but had no effects on interleukin-1beta or tumor necrosis factor-alpha. The therapy with 5% jaboticaba peel improved clinical symptoms (p<0.05) by reducing diarrhea and bleeding. It also reduced by 62% the number of visible tumors and by 40% the incidence of adenoma or adenocarcinoma, while improving crypt distortion and goblet cell depletion. The 2.5% jaboticaba intervention shown mostly benefits to clinical symptoms (p<0.05). Neither intervention statistically reduced the levels of inflammatory mediators. In conclusion, jaboticaba peel showed partial benefits against colitis-linked colorectal cancer, with promising application in clinical trials, given its high content in fibers and cyanidin-3-O-glucoside.