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Toxins 2014, 6(8), 2270-2290; doi:10.3390/toxins6082270

Sub-Emetic Toxicity of Bacillus cereus Toxin Cereulide on Cultured Human Enterocyte-Like Caco-2 Cells

Laboratory of Food Microbiology and Food Preservation, Ghent University, Ghent B-9000, Belgium
Laboratory of Food Chemistry and Human Nutrition, Ghent University, Ghent B-9000, Belgium
Laboratory for Biology and Microbial Genetics, Faculty of Food Technology and Biotechnology, Zagreb University, Zagreb HR-10000, Croatia
Laboratory of Experimental Cancer Research, University Hospital Ghent, Ghent B-9000, Belgium
Laboratory for System Biomedicine and Centre for Proteomics and Mass Spectrometry, "Ruđer Bošković" Institute, Zagreb HR-10000, Croatia
Author to whom correspondence should be addressed.
Received: 2 March 2014 / Revised: 18 July 2014 / Accepted: 22 July 2014 / Published: 4 August 2014
(This article belongs to the Section Bacterial Toxins)
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Cereulide (CER) intoxication occurs at relatively high doses of 8 µg/kg body weight. Recent research demonstrated a wide prevalence of low concentrations of CER in rice and pasta dishes. However, the impact of exposure to low doses of CER has not been studied before. In this research, we investigated the effect of low concentrations of CER on the behavior of intestinal cells using the Caco-2 cell line. The MTT (mitochondrial 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and the SRB (sulforhodamine B) reactions were used to measure the mitochondrial activity and cellular protein content, respectively. Both assays showed that differentiated Caco-2 cells were sensitive to low concentrations of CER (in a MTT reaction of 1 ng/mL after three days of treatment; in an SRB reaction of 0.125 ng/mL after three days of treatment). Cell counts revealed that cells were released from the differentiated monolayer at 0.5 ng/mL of CER. Additionally, 0.5 and 2 ng/mL of CER increased the lactate presence in the cell culture medium. Proteomic data showed that CER at a concentration of 1 ng/mL led to a significant decrease in energy managing and H2O2 detoxification proteins and to an increase in cell death markers. This is amongst the first reports to describe the influence of sub-emetic concentrations of CER on a differentiated intestinal monolayer model showing that low doses may induce an altered enterocyte metabolism and membrane integrity. View Full-Text
Keywords: Bacillus cereus; cereulide; emetic toxin; doses; cell; toxicity; differentiated Caco-2 Bacillus cereus; cereulide; emetic toxin; doses; cell; toxicity; differentiated Caco-2

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Rajkovic, A.; Grootaert, C.; Butorac, A.; Cucu, T.; De Meulenaer, B.; van Camp, J.; Bracke, M.; Uyttendaele, M.; Bačun-Družina, V.; Cindrić, M. Sub-Emetic Toxicity of Bacillus cereus Toxin Cereulide on Cultured Human Enterocyte-Like Caco-2 Cells. Toxins 2014, 6, 2270-2290.

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