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Effects of capsaicin on the chemical initiation of colon carcinogenesis in rats.

Grant number: 14/21951-6
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): December 01, 2015
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luís Fernando Barbisan
Grantee:Brunno Felipe Ramos Caetano
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide), a lipophilic antibacterial, antiinflammatory and antioxidant alkaloid compound, is the major pungent ingredient in red peppers. This study aims at evaluating capsaicin potential chemopreventive effect during the initiation of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats will be randomly allocated into six groups (10-15 animals each). Over the first four weeks, a basal chow or basal chow containing 0.25% and 0.05% capsaicin will be given to groups 1 and 6, 2 and 4 and 3 and 5, respectively. By the end of week 2, all animals will receive four subcutaneous injections of either DMH (groups 1-3, 40mg/kg b.w) or EDTA (groups 4-6, DMH vehicle), twice a week. Thereafter, all animals will receive drinking water and a basal chow ad libitum. Peripheral blood samples will be collected by puncturing the retro-orbital plexus, 4 and 12 hours after the last DMH injection. Genotoxicity testing will be performed by the comet assay. Five animals from each group will be sacrificed 24 hours after the last DMH injection. Colon and liver tissue fragments will be collected and either stored at -80ºC for RNA extraction, or fixed in formaldehyde and stored in 70% ethanol for later. histopathological and immunohistochemical analyses. RNA samples will be analyzed by the TaqMan Low Density Array® (TLDA), which assesses 95 different genes involved in oxidative metabolism, pro- and antioxidant activity, cell proliferation, DNA damage, DNA repair and apoptosis. Ten animals from each group will be sacrificed at the end of week 22. Their colons (medial and distal) will be removed, fixed and stored in 70% ethanol. After fixation, colon specimens will be stained with 0.2% methylene blue for the stereoscopic detection of Aberrant Crypt Foci (ACF, incidence and multiplicity), and histopathological analysis. By the end of this study, we expect to have a better understanding of capsaicin modulation capability in DMH-induced colon carcinogenesis.

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Scientific publications
(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)
RAMOS CAETANO, BRUNNO FELIPE; TABLAS, MARIANA BAPTISTA; IGNOTI, MARCELA GONCALVES; DE MOURA, NELCI ANTUNES; ROMUALDO, GUILHERME RIBEIRO; BARBISAN, LUIS FERNANDO; MARCHESAN RODRIGUES, MARIA APARECIDA. Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine. Environmental Science and Pollution Research, v. 28, n. 2, p. 2457-2467, . (14/21951-6, 14/24762-0)
RAMOS CAETANO, BRUNNO FELIPE; TABLAS, MARIANA BAPTISTA; FERREIRA PEREIRA, NATALIA ELIAS; DE MOURA, NELCI ANTUNES; CARVALHO, ROBSON FRANCISCO; MARCHESAN RODRIGUES, MARIA APARECIDA; BARBISAN, LUIS FERNANDO. Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats. Toxicology and Applied Pharmacology, v. 338, p. 93-102, . (14/24762-0, 14/21951-6)
RAMOS CAETANO, BRUNNO FELIPE; TABLAS, MARIANA BAPTISTA; ROMUALDO, GUILHERME RIBEIRO; MARCHESAN RODRIGUES, MARIA APARECIDA; BARBISAN, LUIS FERNANDO. Early molecular events associated with liver and colon sub-acute responses to 1,2-dimethylhydrazine: Potential implications on preneoplastic and neoplastic lesion development. Toxicology Letters, v. 329, p. 67-79, . (16/12015-0, 14/24762-0, 14/21951-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAETANO, Brunno Felipe Ramos. Effects of capsaicin on the initiation stage of colon cancer in rats. 2017. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.

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