RESUMO

Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2-DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats.

Assuntos

Focos de Criptas Aberrantes/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Dano ao DNA , Hemina/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , 1,2-Dimetilidrazina , Ração Animal , Animais , Células CACO-2 , Cocarcinogênese , Ensaio Cometa , Regulação para Baixo/efeitos dos fármacos , Fezes , Humanos , Masculino , Fosfatidilinositol 3-Quinase/genética , Ratos , Ratos Wistar , Receptor do Fator de Crescimento Transformador beta Tipo II/biossíntese , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Carne Vermelha , Fatores de Tempo , Fator D de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/genética

RESUMO

The risk of developing colorectal cancer (CRC) could be associated with red and processed meat intake. Experimental data supports that hemin iron, found abundantly in red meat, promotes CRC in mice and rats, while indole-3 carbinol (I3C) and synbiotics (syn) exert anti-carcinogenic activities in most studies of colon carcinogenesis. This study aimed to investigate the modifying effects of I3C and syn (inulin + Bifidobacterium lactis), given separately or together, on dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed rats. All animals were given four subcutaneous DMH injections and then, two weeks after carcinogen exposure, they began a basal diet containing hemin, hemin + I3C, hemin + syn, or hemin + I3C + syn for 23 weeks. The combination of I3C + syn significantly increased fecal water genotoxicity, tumor volume and invasiveness when compared to the hemin-fed control group. The groups fed I3C or syn alone had a significant reduction in the number of preneoplastic aberrant crypt foci (ACF) lesions compared to the hemin-fed group. Dietary I3C also reduced fecal water genotoxicity. Gene expression analysis of colorectal tumors demonstrated that the combination of dietary I3C + syn increased transcript levels for Raf1 and decreased tumor progression and invasiveness related to the genes Cdh1 and Appl1. This analysis also revealed that the Tnf and Cdh1 genes were significantly up- and down-regulated, respectively, in tumors of rats that received I3C, in comparison with the hemin-fed group. These findings reveal that the joint administration of I3C and syn enhanced the development of colon tumors induced by DMH in hemin-fed rats, while they potentially reduced ACF development when given alone.

Assuntos

Anticarcinógenos/administração & dosagem , Cocarcinogênese , Neoplasias do Colo/etiologia , Hemina/efeitos adversos , Indóis/administração & dosagem , Carne Vermelha/efeitos adversos , Simbióticos/administração & dosagem , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células CACO-2 , Caderinas/genética , Carcinógenos/toxicidade , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Ensaio Cometa , Dimetilidrazinas/toxicidade , Progressão da Doença , Perfilação da Expressão Gênica , Hemina/administração & dosagem , Humanos , Peroxidação de Lipídeos , Masculino , Invasividade Neoplásica/genética , Proteínas do Tecido Nervoso/genética , Proteínas Proto-Oncogênicas c-raf/genética , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/genética

RESUMO

Yacon (Smallanthus sonchifolius), a perennial plant of the family Asteraceae native to the Andean regions of South America, is an abundant source of fructooligosaccharides (FOS). This comprehensive review of the literature addressed the role of yacon supplementation in promoting health and reducing the risk of chronic diseases. According to several preclinical and clinical trials, FOS intake favors the growth of health-promoting bacteria while reducing pathogenic bacteria populations. Moreover, the endproducts of FOS fermentation by the intestinal microbiota, short chain fatty acids (SCFA), act as substrates or signaling molecules in the regulation of the immune response, glucose homeostasis and lipid metabolism. As a result, glycemic levels, body weight and colon cancer risk can be reduced. Based on these findings, most studies reviewed concluded that due to their functional properties, yacon roots may be effectively used as a dietary supplement to prevent and treat chronic diseases.

Assuntos

Asteraceae/química , Doença Crônica/prevenção & controle , Disbiose/prevenção & controle , Alimento Funcional , Oligossacarídeos/uso terapêutico , Tubérculos/química , Prebióticos , Animais , Doença Crônica/epidemiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/fisiopatologia , Fermentação , Manipulação de Alimentos , Alimento Funcional/efeitos adversos , Alimento Funcional/análise , Microbioma Gastrointestinal/imunologia , Humanos , Oligossacarídeos/análise , Oligossacarídeos/metabolismo , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Prebióticos/efeitos adversos , Prebióticos/análise , Fatores de Risco

RESUMO

Yacon (Smallanthus sonchifolius), a tuberous root native to the Andean region of South America, contains high concentration of fructans with potential for colon cancer prevention. This study investigated the potential beneficial of yacon intake on colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats. After 4 weeks of DMH-initiation, groups were fed basal diet (G1 and G6) or basal diet containing dried extract of yacon root at 0.5% (G2), 1.0% (G3 and G5) or a synbiotic formulation (G4) (1.0% yacon plus Lactobacillus casei at 2.5 × 10(10)CFU per g diet) for 13 weeks. At week 20, a significant reduction in number and multiplicity of aberrant crypt foci (ACF) and in number of invasive adenocarcinomas was observed in the groups orally treated with 1.0% yacon (G3) or the synbiotic formulation (G4) (0.05

Assuntos

Asteraceae , Neoplasias do Colo/prevenção & controle , 1,2-Dimetilidrazina/toxicidade , Animais , Carcinógenos/toxicidade , Proliferação de Células , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar