Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/3045
Título: Insights of enteropathogenic effects of mycotoxins on the human intestinal gut mucosa
Autor: Assunção, Ricardo
Alvito, Paula
Kleiveland, C.
Lea, T.
Palavras-chave: Segurança Alimentar
Toxicologia
Avaliação de Risco
Saúde Humana
Data: Abr-2015
Resumo: Intestinal mucosa is the first biological barrier encountered by natural toxins and it could be exposed to high amounts of dietary mycotoxins1,2. Trichothecenes, ochratoxin A and patulin (PAT) are the best known enteropathogenic mycotoxins able to alter functions of the intestine3. OBJECTIVES: This study aimed to evaluate the effects of PAT, a mycotoxin produced by Penicillium spp. during fruit spoilage, on barrier properties and function of the gut mucosa. METHODOLOGIES: Viability (MTT), proliferation (3H-thymidine incorporation assay), transepithelial electrical resistance (TER), SDS-PAGE and immunoblotting and flow cytometry methodologies were applied in order to characterize the effects of PAT on intestinal cell model (Caco-2), human peripheral blood lymphocytes (PBL) and human blood monocytederived dendritic cells (DC). RESULTS: PAT exposure reduced Caco-2 cell viability at concentrations above 12μM. The integrity of the Caco-2 monolayer was affected by PAT exposure, as demonstrated by a decrease in TER values, becoming more pronounced at 50μM. No effects were detected on the expression levels of the tight junction proteins occludin, claudin-1 and claudin-3 at 50μM. However, the expression of zonula occludens-1 (ZO-1) and myosin light chain (MLC) declined and levels of phospho-MLC increased, after 24h of exposure to 50μM of PAT. T cell proliferation was highly sensitive to PAT with the major effects for concentrations above 10nM of PAT. The same conditions did not affect the maturation of DC. CONCLUSIONS: PAT causes a reduction in Caco-2 barrier function mainly by perturbation of ZO-1 levels and phosphorylation of MLC. Low doses of PAT strongly inhibited T cell proliferation induced by a polyclonal activator, but had no effect on the maturation of DC. These results provide new information that strengthens the concept that the epithelium and immune cells of the intestinal mucosa are important targets for the toxic effects of food contaminants like mycotoxins.
Peer review: yes
URI: http://hdl.handle.net/10400.18/3045
Aparece nas colecções:DAN - Posters/abstracts em congressos internacionais



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