The Mycotoxin Patulin Alters the Barrier Function of the Intestinal Epithelium: Mechanism of Action of the Toxin and Protective Effects of Glutathione

Mahfoud, Radhia; Maresca, Marc; Garmy, Nicolas; Fantini, Jacques

doi:10.1006/taap.2002.9417

Cited by 184 publications

(127 citation statements)

References 41 publications

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“…The observed cytotoxicity of patulin in the present study agrees with that observed by other authors on other cell lines. 6,33 Conversely, desoxypatulinic acid, on the other hand, was not cytotoxic to lymphocytes following 3 h of incubation, for the whole range of concentrations used. Desoxypatulinic acid was slightly toxic only at the highest concentrations tested (50 and 100 μM) and over the longest period of incubation (24 h).…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 84%

“…3À5 The mechanism of patulin toxicity has been proposed to be due to its reactivity with thiol-bearing molecules such as the important cellular antioxidant glutathione. 6,7 Acute symptoms caused by patulin in humans are gastritis and nausea. 2 Therefore, many countries, including the U.S. and those of the European Union, have established maximum tolerable levels of patulin contamination for fruit-derived products.…”

Section: ' Introductionmentioning

confidence: 99%

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Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Castoria¹,

Mannina²,

Duran-Patron

et al. 2011

J. Agric. Food Chem.

127

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ABSTRACT:The infection of stored apples by the fungus Penicillium expansum causes the contamination of fruits and fruit-derived products with the mycotoxin patulin, which is a major issue in food safety. Fungal attack can be prevented by beneficial microorganisms, so-called biocontrol agents. Previous time-course thin layer chromatography analyses showed that the aerobic incubation of patulin with the biocontrol yeast Rhodosporidium kratochvilovae strain LS11 leads to the disappearance of the mycotoxin spot and the parallel emergence of two new spots, one of which disappears over time. In this work, we analyzed the biodegradation of patulin effected by LS11 through HPLC. The more stable of the two compounds was purified and characterized by nuclear magnetic resonance as desoxypatulinic acid, whose formation was also quantitated in patulin degradation experiments. After R. kratochvilovae LS11 had been incubated in the presence of 13 C-labeled patulin, label was traced to desoxypatulinic acid, thus proving that this compound derives from the metabolization of patulin by the yeast. Desoxypatulinic acid was much less toxic than patulin to human lymphocytes and, in contrast to patulin, did not react in vitro with the thiol-bearing tripeptide glutathione. The lower toxicity of desoxypatulinic acid is proposed to be a consequence of the hydrolysis of the lactone ring and the loss of functional groups that react with thiol groups. The formation of desoxypatulinic acid from patulin represents a novel biodegradation pathway that is also a detoxification process.

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Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 84%

Section: ' Introductionmentioning

confidence: 99%

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Castoria¹,

Mannina²,

Duran-Patron

et al. 2011

J. Agric. Food Chem.

127

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“…In the present study, we used patulin at the concentration of 50 µM (7.7 µg/ml), as reported in the previous reports (Mahfoud et al 2002;Liu et al 2007). Such a high concentration may not happen on commercially available apple juice (detected at 5.7-26.0 µg/l) (Rychlik and Schieberle 1999).…”

Section: Discussionmentioning

confidence: 97%

“…Investigations of the mechanism behind the toxicity of patulin have focused primarily on its effects on the stability of TJs (McKinley et al 1982;Mahfoud et al 2002;Kawauchiya et al 2011). Given that the stability of TJ proteins is regulated by their phosphorylation on tyrosine residues, decreased phosphatase activity might account for patulin-mediated increases in the phosphorylation of TJ proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Symptoms of acute toxicity caused by patulin are bleeding from the digestive tract, diarrhea, and brain edema. The acute toxicity of patulin is thought to result from the destruction of tight junctions (TJs) in gastrointestinal tissue (Mahfoud et al 2002). Epithelial cells form barriers such as TJs to block the entry of toxic compounds or bacteria from outside of digestive tract tissues.…”

Section: Introductionmentioning

confidence: 99%

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The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Katsuyama

Konno

Shimoyama

et al. 2014

Tohoku J. Exp. Med.

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Patulin is a mycotoxin that is found mainly in apple products and causes symptoms such as bleeding from the digestive tract and diarrhea. Efforts to elucidate the mechanism of its toxicity have focused on protein tyrosine phosphatases (PTPs), which regulate the function of tight junctions (TJs) in colon epithelial cells. Patulin reacts with the conserved cysteine residues in the catalytic domains of PTP isoforms. Treatment of Caco-2 human colon cancer cells, used as a colon epithelial model, with 50 µM patulin decreased the level of density-enhanced phosphatase-1 (DEP-1) protein to 30% of the control level after 6 h. The level of DEP-1 mRNA was also decreased during 24 h after treatment with patulin. Moreover, knockdown of DEP-1 increased the level of phosphorylated claudin-4. Destruction of TJs by patulin treatment was observed by immunostaining with an antibody against zonula occludens (ZO)-1. To better understand the mechanistic basis of the decrease in DEP-1 mRNA levels, we searched for a cis-element upstream of the DEP-1 gene and found an element responsive to the peroxisome proliferator-activated receptor gamma (PPARγ ) protein. Using a PPARγ-specific antibody, we showed a decrease in PPARγ abundance to 42% of the control level within 6 h after treatment with patulin. PPARγ has four cysteine residues that are involved in zinc finger formation. Our data suggest that DEP-1 affects TJ function and that PPARγ might control DEP-1 expression. Therefore, the toxicity of patulin to cellular functions might be attributable to its ability to down-regulate the expression of DEP-1 and PPARγ.

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Incidences of Mould and Bacterial Toxins in Dairy Products

Wan¹,

Shah²,

El-Nezami³

2016

Microbial Toxins in Dairy Products

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The Mycotoxin Patulin Alters the Barrier Function of the Intestinal Epithelium: Mechanism of Action of the Toxin and Protective Effects of Glutathione

Cited by 184 publications

References 41 publications

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Incidences of Mould and Bacterial Toxins in Dairy Products

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