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Fecal water genotoxicity and development of aberrant crypt foci in male Wistar rats fed heme, indole-3-carbinol and/or symbiotic formulation

Grant number: 13/08033-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2013
Effective date (End): December 31, 2014
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


The present study aims to evaluate the preventive effect of synbiotic (prebiotic inulin associated with the probiotic Bifidobacterium bifidus) and indole-3-carbinol intake on fecal genotoxicity in a colon carcinogenesis model induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats fed a diet containing heme. The animals will be allocated into seven groups (n=10-12 rats each): groups 1-8 and 9 will receive four subcutaneous injections of DMH (40 mg/kg) or EDTA solution (DMH vehicle) in the initial two weeks of the experiment, respectively. Groups 1 and 9 will receive basal diet until the end of the experiment, Groups 2-8 will receive basal diet containing heme (0.32 g / kg diet), basal diet containing heme (0.32 g / kg diet) plus synbiotic (inulin + Bifidobacterium bifidum 2.5 x 108 CFU / kg diet), basal diet containing heme (0.32 g / kg diet) plus indole-3-carbinol (2g/kg diet), basal diet containing synbiotic (inulin + Bifidobacterium bifidum 2.5 x 108 CFU/ kg diet) and basal diet plus Indo-3-carbinol (2g/kg diet), Respectively. The animals will be euthanized on the 22nd week of the experiment. The colon (medial and distal) and fecal content will be collected. The colon will be immersed in a fixative (24h) and stored in 70% alcohol. The colon will be stained with methylene blue 2% for the detection of stereoscopic ACF (incidence and multiplicity). CaCO-2 cells will be exposed to fecal water from different treatments and subsequently analyzed by cell viability, cytotoxicity (MTT), and genotoxicity assays (comet assay). The findings will be compared using ANOVA or Kruskal Wallis test. (AU)

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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)
DE MOURA, NELCI A.; CAETANO, BRUNNO F. R.; DE MORAES, LEONARDO N.; CARVALHO, ROBSON F.; RODRIGUES, MARIA A. M.; BARBISAN, LUIS F.. Enhancement of colon carcinogenesis by the combination of indole-3 carbinol and synbiotics in hemin-fed rats. Food and Chemical Toxicology, v. 112, p. 11-18, . (13/08033-5, 12/12631-2, 11/23699-4)
DE MOURA, NELCI A.; CAETANO, BRUNNO F. R.; BIDINOTTO, LUCAS T.; RODRIGUES, MARIA A. M.; BARBISAN, LUIS F.. Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 846, . (11/23699-4, 12/12631-2, 13/08033-5)
DE MOURA, N. A.; CAETANO, B. F. R.; BIDINOTTO, L. T.; RODRIGUES, M. A. M.; BARBISAN, L. F.. Synbiotic supplementation attenuates the promoting effect of indole-3-carbinol on colon tumorigenesis. BENEFICIAL MICROBES, v. 12, n. 5, p. 493-501, . (13/08033-5, 12/12631-2, 11/23699-4)

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