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Analisys of correlation among histological aspects, p53 expression and DNA damage in mucosal cells from animals submited to diversion colitis

Abstract

Exclusion colitis is a disease characterized by the development of a chronic inflammatory process in the mucosa of segments of the large intestine in which there is no intestinal transit. This disease presents clinical, endoscopic and histological features similar to those of intestinal inflammatory diseases, thus suggesting common etiopathogenesis. It arises in relation to deficiencies in short-chain fatty acids in the intestinal lumen; these fatty acids are the main energy substrate needed for the metabolism of the colon mucosa cells. The formation of free radicals as a result of metabolic alterations inside the lumen of the intestinal segment excluded from the transit has an important role in triggering and maintaining the intestinal inflammatory process, because these free radicals cause progressive oxidative damage to the DNA of the colon mucosa cells. The deficiency in short-chain fatty acids in the intestinal lumen causes an inflammatory process in the colon mucosa, oxidative damage to the DNA and alterations to the regulation pathways for the cell cycle. This induces the expression of genes responsible for the growth, differentiation and apoptosis of colonocytes. Because progressive oxidative damage interferes in the expression of genes related to controlling the cell cycle, this is one of the initial phenomena in the triggering of the inflammatory process. Its correlation with the development of dysplasia and neoplasia among individuals with intestinal inflammatory disease has been demonstrated. Although the histological characteristics are similar, no experimental studies have yet been conducted on the correlation between oxidative damage to DNA and inflammatory alterations to colon mucosa cells, in individuals with exclusion colitis. Likewise, it is still unclear whether colorectal dysplasia and neoplasia arise as a result of alterations in the expression of genes and proteins that regulate the cell cycle, caused by oxidative damage to DNA, in animals subjected to exclusion colitis. The objective of the present study was to experimentally verify whether the length of time for which the intestinal transit has been excluded has any influence on the oxidative damage to the DNA, the histological alterations and the alterations to p53 protein expression, in the colon of rats subjected to intestinal transit exclusion. (AU)

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Scientific publications (6)
(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)
ANTONIO JOSÉ TIBURCIO ALVES JÚNIOR; JOSÉ AIRES PEREIRA; ADRIELI HELOÍSA CAMPARDO PANSANI; DANIELA OLIVEIRA MAGRO; CLÁUDIO SADDY RODRIGUES COY; CARLOS AUGUSTO REAL MARTINEZ. Tissue sulfomucin and sialomucin content in colon mucosa without intestinal transit subjected to intervention with Curcuma longa (curcumin). Acta Cirurgica Brasileira, v. 32, n. 3, p. 182-193, Mar. 2017. Web of Science Citations: 2.
RODRIGO DE OLIVEIRA MELLO; CAMILA MORAIS GONÇALVES DA SILVA; FÁBIO PIOVEZAN FONTE; DANIELE LUCHINITZ FERRAZ SILVA; JOSÉ AIRES PEREIRA; NELSON FONTANA MARGARIDO; CARLOS AUGUSTO REAL MARTINEZ. Avaliação do número de células caliciformes nas criptas da mucosa colônica com e sem trânsito intestinal. Rev. Col. Bras. Cir., v. 39, n. 2, p. 139-145, Abr. 2012.
CALTABIANO, CAROLINE; MAXIMO, FELIPE RODRIGUES; SPADARI, ANA PAULA PIMENTEL; DA CONCEICAO MIRANDA, DANIEL DUARTE; PIVATTO SERRA, MARCIA MILENA; RIBEIRO, MARCELO LIMA; REAL MARTINEZ, CARLOS AUGUSTO. 5-Aminosalicylic Acid (5-ASA) Can Reduce Levels of Oxidative DNA Damage in Cells of Colonic Mucosa With and Without Fecal Stream. Digestive Diseases and Sciences, v. 56, n. 4, p. 1037-1046, APR 2011. Web of Science Citations: 13.
CARLOS AUGUSTO REAL MARTINEZ; RONALDO NONOSE; ANA PAULA PIMENTEL SPADARI; FELIPE RODRIGUES MÁXIMO; DENISE GONÇALVES PRIOLLI; JOSÉ AIRES PEREIRA; NELSON FONTANA MARGARIDO. Quantification by computerized morphometry of tissue levels of sulfomucins and sialomucins in diversion colitis in rats. Acta Cirurgica Brasileira, v. 25, n. 3, p. 231-240, Jun. 2010.
NONOSE, RONALDO; PIMENTEL SPADARI, ANA PAULA; PRIOLLI, DENISE GONCALVES; MAXIMO, FELIPE RODRIGUES; PEREIRA, JOSE AIRES; REAL MARTINEZ, CARLOS AUGUSTO. Tissue quantification of neutral and acid mucins in the mucosa of the colon with and without fecal stream in rats. Acta Cirurgica Brasileira, v. 24, n. 4, p. 267-275, JUL-AUG 2009. Web of Science Citations: 19.
MARCOS VIEIRA DE SOUSA; DENISE GONÇALVES PRIOLLI; ADRIANA VALIM PORTES; IZILDA APARECIDA CARDINALLI; JOSÉ AIRES PEREIRA; CARLOS AUGUSTO REAL MARTINEZ. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats. Acta Cirurgica Brasileira, v. 23, n. 5, p. 417-424, Out. 2008.

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