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Chemopreventive activity of capsaicin on the initiation and/or promotion stages of rat colon carcinogenesis

Abstract

Capsaicin (8-methyl-N-vanillyl-(trans)-6-nonenamide), the major pungent ingredient in red peppers, is an alkaloid with anti-bacterial, anti-inflammatory and antioxidant properties. This study aims at evaluating the potential chemopreventive effect of capsaicin on the initiation and promotion/progression stages of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats will be allocated into 12 groups (10-15 animals each) and will receive basal chow containing 0.25% or 0.05% capsaicin before and during DMH treatment (Initiation protocol) or after carcinogen treatment (Promotion protocol). In the initiation protocol, genotoxicity will be evaluated by the comet assay in blood samples collected 4 and 12 hours after the last DMH injection. Five animals from each group will be sacrificed 24 hours after the last DMH injection and the remaining will be examined 20 weeks after carcinogen treatment for tumor development and aberrant crypt foci (ACF). In the promotion protocol the colon will be analyzed 20 weeks after carcinogen treatment for tumor incidence, multiplicity and histopathological patterns. ACF will be scored stereoscopically for number and crypt multiplicity in methylene blue stained whole-mount preparations of the medial and distal colon. Samples from colon tumors, distal colon and liver will be stored for RNA extraction, or fixed in buffered formalin for histopathological and immunohistochemical analyses. Cell proliferation and apoptosis will be analysed immunohistochemically by Ki-67 and caspase-3. The pattern of beta-catenin expression will be evaluated in the neoplastic lesions of the colon. RNA expression for genes involved in oxidative metabolism with pro- and antioxidant activity, DNA damage and repair, cell proliferation and apoptosis, tumor invasion and metastasis will be analyzed by the TaqMan Low Density Array® (TLDA). At the end of this study, we expect to have a better understanding of the potential chemopreventive activity of capsaicin on the initiation and/or promotion stages of rat colon carcinogenesis. (AU)

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; 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, SEP 1 2020. Web of Science Citations: 0.
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 SEP 2020. Web of Science Citations: 1.
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, JAN 1 2018. Web of Science Citations: 3.

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