Preventive effects of the consumption of freeze-dried jaboticaba peel in BALB/c mice with Colorectal Cancer induced by azoxymethane/dextran sodium sulfate

• Grant number: 19/03228-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date until: August 01, 2021
• End date until: June 30, 2024
• Field of knowledge: Agronomical Sciences - Food Science and Technology - Food Science
• Principal Investigator: Mário Roberto Maróstica Junior
• Grantee: Roberto de Paula do Nascimento
• Host Institution: Faculdade de Engenharia de Alimentos (FEA). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 22/10485-0 - Freeze-dried jaboticaba peel for colorectal cancer prevention: mechanisms in wild type and genetically modified mice, BE.EP.DR

Abstract

Colorectal Cancer (CRC) is one of the most frequent and deadly types of Cancer in the world. In Brazil, in the last decade, the cases of CRC augmented considerably, and by 2030, an increase of up to 80% in incidence is foreseen in Latin America. The individuals with higher risk for obtaining CRC are those with obesity, diabetes and especially inflammatory bowel diseases (ulcerative colitis and Crohn's disease), suggesting about the role of inflammation in the course of CRC. Associated with this, eating habits have also been implicated as risk factors for CRC. High fruit intake seems to contribute to a significant decrease in the risk for CRC. Especially, Brazilian fruits, as recent studies show, seem to present preventive and/or therapeutic effects against chronic diseases and Cancer. Jabuticaba (Myrciaria jaboticaba), from Atlantic Forest, is one of the native fruits that have important amounts of insoluble fibers and anthocyanins, which are bioactive compounds with antioxidant, antiinflammatory and antiproliferative activities. Especially, the jaboticaba peel have been used by our group, with satisfactory results, in animal models of obesity and hepatic steatosis, however, it has not yet been tested in a robust animal model of CCR by any research group. In the investigation of the effects of chemopreventive agents, such as jaboticaba, in CRC associated with inflammation, the induction of the disease through the use of azoxymethane associated with dextran sodium sulfate seems to be the most practical and cost-effective method. Thus, considering the above, this work has as main objective to evaluate the effects of the preventive consumption of a Brazilian native fruit, jaboticaba, in a robust model of CRC associated with inflammation. For this, BALB/c mice will be used in experimentation. Mice will receive, added to the AIN-93M diet, the freeze-dried powder of the jaboticaba peel at 0, 2,5, 5, 7,5 or 10% concentrations, from the beginning until the end of the experiment. The carcinogenic azoxymethane will be administered intraperitoneally in a single dose of 10 mg/kg, and seven days later, the inductor of colitis, dextran sodium sulfate, will be added to the drinking water, at 2%, for another seven days. The experiment will be finalized after 16 weeks from the single injection of azoxymethane, in order to obtain a successful model with formation of adenomas and/or carcinomas. The following analyzes will be performed: 1. clinical activity of the disease (bleeding, stool consistency, weight loss); 2. tissue measurements in colon (length, mass); 3. incidence, multiplicity and size of tumors; 4. concentration or expression of proteins involved in CRC (Beta-catenin, APC, KRAS, ERK1/2, p53, COX-2, iNOS, Nf-kB, STAT3, TNF-alfa, IL-1beta, IL-6 and TGF-beta); and 5. concentration of short chain fatty acids, which are substrates that protect the intestinal mucosa and regulate signaling pathways. It is expected that the peel of jaboticaba, which is the portion of the fruit with most fiber and phenolic compounds, will be able to attenuate or eliminate the clinical and immunophysiopathological damages of the CRC experimental model. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO, ANA PAULA DA FONSECA; DO NASCIMENTO, ROBERTO DE PAULA; ALVES, MARIANA DA ROCHA; REGUENGO, LIVIA MATEUS; MAROSTICA JUNIOR, MARIO ROBERTO. razilian tucuma-do-Amazonas (Astrocaryum aculeatum) and tucuma-do-Para (Astrocaryum vulgare) fruits: bioactive composition, health benefits, and technological potentia. Food Research International, v. 151, JAN 2022. (18/11069-5, 19/25048-2, 19/03228-9, 17/23657-6, 15/50333-1, 15/13320-9)

CARLA, DYANA; ALVES, MARIANA DA ROCHA; NOGUERA, NATHAN HARGREAVES; DO NASCIMENTO, ROBERTO DE PAULA. A review on Brazilian baru plant (Dipteryx alata Vogel): morphology, chemical composition, health effects, and technological potential. FUTURE FOODS, v. 5, p. 16-pg., 2022-06-01. (19/03228-9)

DO NASCIMENTO, ROBERTO DE PAULA; REGUENGO, LIVIA MATEUS; DA FONSECA MACHADO, ANA PAULA; MAROSTICA JUNIOR, MARIO ROBERTO. he preventive and therapeutic potential of native Brazilian fruits on colorectal cance. FOOD BIOSCIENCE, v. 46, APR 2022. (18/11069-5, 19/03228-9, 17/23657-6, 15/50333-1, 19/25048-2, 15/13320-9)

DO NASCIMENTO, ROBERTO DE PAULA; RIZZATO, JULIA SOTO; POLEZI, GABRIELE; MOYA, AMANDA MARIA TOMAZINI MUNHOZ; SILVA, MILENA FERREIRA; MACHADO, ANA PAULA DA FONSECA; FRANCHI JUNIOR, GILBERTO CARLOS; BORGUINI, RENATA GALHARDO; SANTIAGO, MANUELA CRISTINA PESSANHA DE ARAUJO; PAIOTTI, ANA PAULA RIBEIRO; et al. Freeze-dried jaboticaba (Myrciaria jaboticaba) peel powder, a rich source of anthocyanins and phenolic acids, mitigates inflammation-driven colorectal cancer in mice. FOOD BIOSCIENCE, v. 53, p. 10-pg., 2023-04-05. (15/13320-9, 20/00414-3, 19/03228-9, 15/50333-1, 17/23657-6, 18/11069-5)

REGUENGO, LIVIA MATEUS; DO NASCIMENTO, ROBERTO DE PAULA; MACHADO, ANA PAULA DA FONSECA; MAROSTICA JUNIOR, MARIO ROBERTO. Signaling pathways and the potential anticarcinogenic effect of native Brazilian fruits on breast cancer. Food Research International, v. 155, p. 13-pg., 2022-05-01. (15/13320-9, 18/11069-5, 19/03228-9, 17/23657-6, 15/50333-1, 19/25048-2, 19/12244-8)

MACHADO, ANA PAULA DA FONSECA; ALVES, MARIANA DA ROCHA; NASCIMENTO, ROBERTO DE PAULA DO; REGUENGO, LIVIA MATEUS; MAROSTICA JR, MARIO ROBERTO. Antiproliferative effects and main molecular mechanisms of Brazilian native fruits and their by-products on lung cancer. Food Research International, v. 162, p. 9-pg., 2022-12-01. (17/23657-6, 19/03228-9, 15/50333-1, 19/12244-8, 15/13320-9, 18/11069-5)

DO NASCIMENTO, ROBERTO DE PAULA; MACHADO, ANA PAULA DA FONSECA. The preventive and therapeutic effects of anthocyanins on colorectal cancer: A comprehensive review based on up-to-date experimental studies. Food Research International, v. 170, p. 27-pg., 2023-05-30. (19/03228-9, 22/10485-0)