RESUMO
Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.
Assuntos
Neoplasias Colorretais , Resistina , Humanos , Adulto , Neoplasias Colorretais/metabolismo , Adiponectina , Fator de Necrose Tumoral alfa , Dieta , Mucosa Intestinal/metabolismoRESUMO
Whereas the mechanisms underlying the association of toxic dietary xenobiotics and cancer risk are not well established, it is plausible that dietary pattern may affect the colon environment by enhancing or reducing exposure to mutagens. This work aimed to investigate the association between xenobiotics intake and different stages of intestinal mucosal damage and colorectal cancer (CRC) screening and examine whether these associations may be mediated by altered intestinal mutagenicity. This was a case control study with 37 control subjects, 49 patients diagnosed with intestinal polyps, and 7 diagnosed with CRC. Lifestyle, dietary, and clinical information was registered after colonoscopy. For xenobiotics intake estimation the European Prospective Investigation into Cancer (EPIC) and the Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) databases were used. The mutagenicity of fecal supernatants was assayed by the Ames test and light microscopy was used for the presence of aberrant crypt formation. Among all the potential carcinogens studied, the polyp group showed higher intakes of ethanol and dibenzo (a) anthracene (DiB(a)A). Besides, intakes between 0.75 and 1.29 µg/d of total polycyclic aromatic hydrocarbons (PAHs) were related with a higher risk of belonging to the polyp group. On the contrary, an intake of wholegrain cereals greater than 50 g/d was associated with a reduction in the relative risk of belonging to the polyp group. Heterocyclic amines (HAs) such as 2-amino-1-methyl-6-phenylimidazo (4,5,b) pyridine (PhIP) were associated with an increased level of mutagenicity in polyps. This study is of great interest for the identification of possible therapeutic targets for the early prevention of colon cancer through diet.
Assuntos
Neoplasias Colorretais , Mutagênicos , Aminas/toxicidade , Carcinógenos , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Manipulação de Alimentos , Humanos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Estudos Prospectivos , Xenobióticos/toxicidadeRESUMO
Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition.
Assuntos
Estradiol/farmacologia , Estrogênios/farmacologia , Genisteína/farmacologia , Resistência à Insulina , Memória/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Análise de Variância , Animais , Quimioterapia Combinada , Terapia de Reposição de Estrogênios/métodos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Ovariectomia , Fitoestrógenos/farmacologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: Placenta plays a central role in fetal nutrition. During gestational diabetes mellitus (GDM), it suffers structural and functional alterations which affect the health of both mother and fetus. In the present study we aimed to clarify if GDM modifies the amounts of leptin receptor (Ob-R) and of the main proteins implicated in insulin signal transmission (insulin receptor, insulin receptor substrate-1 and phosphatidylinositol-3-kinase subunit p85alpha) in human placenta; we also attempted to confirm the presence of estrogen receptor-alpha to determine the effect of GDM on its amount. METHODS: Placentas were recovered from 30 women with uncomplicated pregnancies and 20 women who developed GDM. Western blotting and immunocytochemistry experiments were performed to investigate the above-mentioned proteins. RESULTS: We observed that all proteins studied were increased in GDM. However, it is unknown if this is a consequence of GDM or the result of medical treatments used to mitigate the injurious effects of GDM. CONCLUSIONS: Probably, the changes we found are indicative of the protective role of the placenta prior to the injurious effects of GDM and/or an important indicator of placental aging. Some aspects related to the link between non-genomic estrogen action, the mitogenic action of insulin and the role of Ob-R in placenta from normal and GDM women need to be investigated in greater depth.