Absorption, Distribution and Excretion
The absorption and degradation of the mycotoxin patulin in man was quantified by using a recently developed stable isotope dilution assay. Application of this currently most sensitive method revealed a patulin content less than 200 ng/L in the blood serum of five consumers of apple juice. Likewise, no patulin was found in the serum of a volunteer, whose blood was drawn shortly after consumption of a juice containing a maximum tolerable amount of patulin. In further in vitro experiments, the degradation of patulin by reacting it with whole blood was investigated. After addition of 100 ug patulin to 9 mL blood, only 6.1% of the mycotoxin was detected after 2 min. It was concluded, therefore, that even high naturally occurring concentrations of patulin in foods are quickly degraded before reaching other tissues than the gastrointestinal tract.
Adult rats of both sexes were given a single oral dose of (14)C-patulin and were sacrificed at various time intervals from 4 hours to 7 days following administration of the mycotoxin. The treated group was exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41 to 66 weeks after weaning, while the controls were given the buffer only throughout gestation and for 38 to 81 weeks after weaning. Approximately 49% of the administered (14)C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hours. All of the (14)C activity detected in the urine samples was either metabolites and/or conjugates of the original (14)c-patulin. About 1-2% of the total radioactivity was recovered as (14)CO2 from expired air. (14)C radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.

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Metabolism / Metabolites
A gas-liquid chromatographic system which allows most of the metabolites of the patulin pathway to be separated and quantitated has been developed. The metabolites are mostly phenols ... The detection limits for the three phenolic acids, 6-methylsalicylic acid, m-hydroxybenzoic acid and gentisic acid are all markedly lower than those obtained in previous systems ...
Metabolism of patulin is limited. No metabolic products have been identified. It is quite likely that the metabolic fragments or conjugated metabolites of patulin either are bound to the cell membrane or become incorporated into the cellular components. (L1943)

[1]. Biosynthesis and toxicological effects of patulin. Toxins (Basel). 2010 Apr;2(4):613-31.

[2]. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796-801.

[3]. Patulin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis and Impaired Mitophagy in HepG2 Cells. J Agric Food Chem. 2018 Nov 21;66(46):12376-12384.

[4]. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796-801.

Patulin is a furopyran and lactone that is (2H-pyran-3(6H)-ylidene)acetic acid which is substituted by hydroxy groups at positions 2 and 4 and in which the hydroxy group at position 4 has condensed with the carboxy group to give the corresponding bicyclic lactone. A mycotoxin produced by several species of Aspergillus and Penicillium, it has antibiotic properties but has been shown to be carcinogenic and mutagenic. It has a role as an antimicrobial agent, a mycotoxin, a carcinogenic agent, a mutagen, a Penicillium metabolite and an Aspergillus metabolite. It is a furopyran, a lactol and a gamma-lactone.
Patulin has been reported in Trichoderma virens, Amesia atrobrunnea, and other organisms with data available.
Patulin is found in pomes. Mycotoxin, found as a contaminant of foods, e.g. apple juice. Sometimes detd. in apple juice Patulin is a mycotoxin produced by a variety of molds, particularly Aspergillus and Penicillium. It is commonly found in rotting apples, and the amount of patulin in apple products is generally viewed as a measure of the quality of the apples used in production. It is not a particularly potent toxin, but a number of studies have shown that it is genotoxic, which has led to some theories that it may be a carcinogen, though animal studies have remained inconclusive. Patulin is also an antibiotic. Several countries have instituted patulin restrictions in apple products. The World Health Organization recommends a maximum concentration of 50 ug/L in apple juice.

Patulin has been shown to exhibit apoptotic and antibiotic functions (A7849, A7850).

Patulin belongs to the family of Pyrans. These are compounds containing a pyran ring, which is a six-member heterocyclic, non-aromatic ring with five carbon atoms, one oxygen atom and two ring double bonds.
4-Hydroxy-4H-furo(3,2-c)pyran-2(6H)-one. A mycotoxin produced by several species of Aspergillus and Penicillium. It is found in unfermented apple and grape juice and field crops. It has antibiotic properties and has been shown to be carcinogenic and mutagenic and causes chromosome damage in biological systems.

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Mechanism of Action
Patulin (PAT) led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 uM PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 hr incubation with 0.05 uM of PAT. Treatment of human PBMCs for 30 min with 30 uM PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 uM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression.
Exposure of human embryonic kidney (HEK293) cells to patulin (PAT) led to a dose- and time-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), p38 kinase and c-Jun N-terminal kinase (JNK). The phosphorylated forms of MAPK kinase 4 (MKK4), c-Jun, and ATF-2 were also seen in PAT-treated cultures. The cell death caused by PAT was significantly reduced by the p38 kinase inhibitor, SB203580, but not by the JNK inhibitor, SP600125. Neither p38 kinase nor JNK played a role in the PAT-induced DNA damage. In PAT-treated cells, inactivation of double-stranded RNA-activated protein kinase R (PKR) by the inhibitor, adenine, markedly suppressed JNK and ERK phosphorylation. Treatment of HEK293 cells with PAT-cysteine adduct, a chemical derivative of PAT, showed no effect on MAPK signaling pathways, cell viability, or DNA integrity. These results indicate that PAT causes rapid activation of p38 kinase and JNK in HEK293 cells, but only the p38 kinase signaling pathway contributes to the PAT-induced cell death. PKR also plays a role in PAT-mediated MAPK activation.
/The effects of patulin (PAT)/ on oxidative stress in various mammalian cell lines were investigated. When cell-permeating fluorescent dyes were used as indicators of the generation of reactive oxygen species (ROS) ... PAT treatment directly increased intracellular oxidative stress in human embryonic kidney (HEK293) and human promyelocytic leukemia (HL-60) cells. Lipid peroxidation levels were also significantly increased in HL-60 cells and mouse kidney homogenates treated with PAT. Suppression of CuZn-superoxide dismutase (SOD) expression in mammalian cells by small interfering RNA resulted in an increase in PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase led to a reduction in damage, indicating the involvement of ROS in PAT toxicity. Pretreatment of HEK293 cells with Tiron, a free radical scavenger, reduced the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 elicited by PAT. The ERK1/2 signaling pathway inhibitor, U0126, also significantly decreased the levels of ROS associated with PAT treatment. These findings indicate that PAT treatment results in the ROS production in mammalian cells, and ROS partially contributes to PAT-induced cytotoxicity. Activation of ERK1/2 signaling pathway is correlated with PAT-mediated ROS.
Patulin caused a dose-dependent inhibition of Na+-K+ ATPase activity in mouse brain and kidney tissue. In vitro and in vivo results suggest possible patulin-mediated effects in the mouse through disruption of ATPase systems.

C7H6O4

154.1201

154.026

149-29-1

Patulin-13C7;1353867-99-8

4696

White to off-white solid powder

1.5±0.1 g/cm3

513.7±50.0 °C at 760 mmHg

108-111 °C

226.8±23.6 °C

0.0±3.0 mmHg at 25°C

1.603

-0.75

1

4

0

11

264

0

ZRWPUFFVAOMMNM-UHFFFAOYSA-N

InChI=1S/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2

4-hydroxy-4,6-dihydrofuro[3,2-c]pyran-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~648.85 mM)
H2O : ~50 mg/mL (~324.42 mM)

Solubility in Formulation 1: 2.5 mg/mL (16.22 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)