Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins

Gao, Yanan; Wang, J.Q.; Li, S.L.; Zhang, Y.D.; Zheng, Nan

doi:10.1016/j.fct.2016.07.019

Cited by 57 publications

(39 citation statements)

References 59 publications

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“…A polarized epithelial monolayer of differentiated Caco-2 cells was formed by replacing the medium every other day for 21 days. Because an MRL for OTA in milk has not yet been established and previous studies have indicated that OTA and aflatoxin M1 (AFM1) have the same cytotoxicity in human intestinal Caco-2 cells [82], we chose the concentration of 0.0005 µg/mL for OTA, based on the Chinese (0.5 µg/kg) limits for AFM1 in milk. We established a concentration gradient when measuring cell viability and transepithelial electrical resistance [83] and chose the 4 µg/mL concentration to investigate the effect of an upper concentration limit on intestinal injury, without affecting cell survival.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Yang

Gao

Yan

et al. 2019

Toxins

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Ochratoxin A (OTA), an important mycotoxin that occurs in food and animal feed, has aroused widespread concern in recent years. Previous studies have indicated that OTA causes nephrotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, cytotoxicity, and neurotoxicity. The intestinal toxicity of OTA has gradually become a focus of research, but the mechanisms underlying this toxicity have not been described. Here, differentiated Caco-2 cells were incubated for 48 h with different concentrations of OTA and transcriptome analysis was used to estimate damage to the intestinal barrier. Gene expression profiling was used to compare the characteristics of differentially expressed genes (DEGs). There were altogether 10,090 DEGs, mainly clustered into two downregulation patterns. The Search Tool for Retrieval of Interacting Genes (STRING), which was used to analyze the protein–protein interaction network, indicated that 24 key enzymes were mostly responsible for regulating cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was used to validate eight genes, three of which were key genes (CASP3, CDC25B, and EGR1). The results indicated that OTA dose-dependently induces apoptosis in differentiated Caco-2 cells. Transcriptome analysis showed that the impairment of intestinal function caused by OTA might be partly attributed to apoptosis, which is probably associated with downregulation of murine double minute 2 (MDM2) expression and upregulation of Noxa and caspase 3 (CASP3) expression. This study has highlighted the intestinal toxicity of OTA and provided a genome-wide view of biological responses, which provides a theoretical basis for enterotoxicity and should be useful in establishing a maximum residue limit for OTA.

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Section: Cell Culture and Treatmentsmentioning

confidence: 99%

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Yang

Gao

Yan

et al. 2019

Toxins

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“…The established MRL of AFM1 is 0.05 μg/kg in the European Union (EU) and 0.5 μg/kg in China and the United States of America (USA). We previously showed that OTA exerts a toxicity similar to that of AFM1 on human intestinal cells [ 8 ]. Furthermore, the IARC has classified OTA as a Group 2B carcinogen, suggesting that it is a possible human carcinogen [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Gao

Wang

et al. 2017

Toxins

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Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM) and OTA (0.2 and 20 μM) individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC)-dextrans (4 and 40 kDa) and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ) proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1), and p44/42 mitogen-activated protein kinase (MAPK) partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05) than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.

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“…Care is always taken to protect infant foods from any of the harmful compounds due to the fact that these food items are consumed by one of the most vulnerable age groups of people i.e., infants. Mycotoxin contamination in food chain is considered as one of the brazen food safety issues worldwide (Bouaziz et al , 2013; Gao et al , 2016; Li et al , 2014; Pattono et al , 2011; Tatay et al , 2014). However, it is still reported that these infant formulas include a number of toxic compounds, such as aflatoxins (Torović, 2015), heavy metals (Fernandes et al , 2015), melamine (Meng et al , 2015; Yang et al , 2016), residues of hormones (Barreiro et al , 2015), nitrates (Chamandust et al , 2016), antibiotics (Díaz-Bao et al , 2015) and pesticide residues (Bessaire et al , 2015; Sharma et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

Determination of Aflatoxin M₁ and Heavy Metals in Infant Formula Milk Brands Available in Pakistani Markets

Akhtar

Shahzad

Yoo

et al. 2017

Korean Journal for Food Science of Animal Resources

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Aflatoxin M1 (AFM1) after its bioconversion from aflatoxin B1 in animal liver becomes the part of milk while heavy metals get entry into milk and milk products during handling in the supply chain. Aflatoxin M1 and heavy metals being toxic compounds are needed to be monitored continuously to avoid any ailments among consumers of foods contaminated with such toxicants. Thirteen commercially available infant formula milk (IFM) brands available in Pakistani markets were analyzed for the quantitative determination of AFM1 and heavy metals through ELISA and atomic absorption spectrophotometer, respectively. AFM1 was found positive in 53.84% samples while 30.76% samples were found exceeding the maximum EU limit i.e. 0.025 μg/kg for AFM1 in IFM. Heavy metals lead (Pb) and cadmium (Cd) were found below the detection limits in any of the sample, whereas the concentrations of iron (Fe), zinc (Zn) and nickel (Ni) ranged between 45.40-97.10, 29.72-113.50 and <0.001-50.90 μg/kg, respectively. The concentration of Fe in all the tested brands was found in normal ranges while the concentrations of Zn and Ni were found exceeding the standard norms. Elevated levels of AFM1, Zn and Ni in some of the tested IFM brands indicated that a diet completely based on these IFM brands might pose sever health implications in the most vulnerable community i.e., infants.

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Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins

Cited by 57 publications

References 59 publications

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Determination of Aflatoxin M₁ and Heavy Metals in Infant Formula Milk Brands Available in Pakistani Markets

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Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins

Cited by 57 publications

References 59 publications

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Determination of Aflatoxin M1 and Heavy Metals in Infant Formula Milk Brands Available in Pakistani Markets

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Determination of Aflatoxin M₁ and Heavy Metals in Infant Formula Milk Brands Available in Pakistani Markets