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At least 19 recordsLinked to original sources
PubMed2000

Induction of micronuclei and chromosomal aberrations by the mycotoxin patulin in mammalian cells: role of ascorbic acid as a modulator of patulin clastogenicity.

Patulin is a mycotoxin produced by several species of Penicillium, Aspergillus and BYSSOCHLAMYS: Patulin is a common contaminant of ripe apples used for the production of apple juice concentrates and is also present in other fruits, vegetables and food products. Patulin has been reported to have mutagenic, carcinogenic and teratogenic properties. Nevertheless, these properties are still a matter of debate. In this report, we further investigated the genotoxicity of patulin in mammalian cells by two different approaches. Firstly, we evaluated the induction of micronuclei in cytokinesis-blocked human lymphocytes. This approach is important because available data concerning the genetic toxicity of patulin in human cells is sparse. Secondly, we chose an established model for patulin genotoxicity, i.e. the chromosomal aberration assay in V79 Chinese hamster cells, to clarify whether concomitant exposure to ascorbic acid with the mycotoxin modulates or not the clastogenicity of patulin. The results unequivocally show induction of DNA-damaged cells by patulin as assessed by both cytogenetic assays. In addition, an almost complete abolition of patulin (0.8 microM) clastogenicity was observed in the presence of 80 microM ascorbic acid (P < 0.05), showing that although a genetic risk is present, ascorbic acid could somehow partially modulate this problem.

Animals↗
PubMed2002

Hplc detection of patulin in apple juice with GC/MS confirmation of patulin identity.

The official patulin LC procedure was further examined (AOAC 995.10). Juice or juice concentrate was extracted with ethyl acetate and cleaned up with sodium carbonate. Patulin in the dried extract was determined by reversed-phase LC with UV detection (280 nm) in 1% THF aqueous solution after evaporation of the ethyl acetate. An end-capped C18 column was required to separate patulin from hydroxymethylfurfural. Patulin was detected in approximately half of the >1000 extracts examined. Only ca 10% of the extracts contained patulin at levels greater than 50 microg/L (50 ppb). Some presumptive findings were confirmed by capillary gas chromatography/mass spectrometry as the trimethyl silyl derivative using electron ionization or as underivatized patulin using negative ion chemical ionization. Trifluoropropylmethyl polysiloxane capillary columns provided superior gas chromatography of underivatized patulin compared to phenyl/methyl polysiloxane and methyl polysiloxane columns.

Beverages↗
PubMed1982

The effects of patulin and patulin-cysteine mixtures on DNA synthesis and the frequency of sister-chromatid exchanges in human lymphocytes.

The effects of patulin and patulin-cysteine mixtures on DNA synthesis in human blood lymphocytes were measured by assaying incorporation of [3H]thymidine into cellular DNA. Patulin inhibited and patulin-cysteine mixtures stimulated the incorporation of [3H]thymidine into DNA. The inhibitory action of patulin diminished with time in culture. Patulin was found to be unstable in the culture medium. The sister-chromatid exchange (SCE) frequency was significantly elevated by intermediate concentrations (0 . 1-0 . 2 micrograms/ml culture) of the toxin. The cells are protected from the effect at low concentrations of the toxin. There may be excessive damage at higher concentrations but only the unaffected cells go into mitosis. Therefore an increased frequency of SCEs is detected only at intermediate concentrations, or, at higher concentrations, with early harvesting. Cysteine seems to potentiate the effect of patulin on SCE frequency.

Crossing Over, Genetic↗
PubMed1994

Antitumoral activity of patulin and patulin-cysteine adducts.

A comparison between the cytotoxicity and the anti-tumoral activity of patulin and patulin-cysteine adducts has been conducted. In vitro assays using L 1210 and P 388 cells showed that patulin-cysteine adducts had less cytotoxic activity than patulin (IC50 was 4 fold of IC50 patulin). In vivo, cysteine not only reduced the toxicity of patulin but also reduced its antitumoral activity against L 1210 and P 388 mouse leukemias (respectively of 25.7% and 46.6% with 3 mg.kg-1.d-1). By addition on patulin at the 4 or 7 position, cysteine might interfere with the lactone function and the -CH2- in in position 6 which are responsible for the antitumoral activity.

Animals↗
PubMed1978

Comparison of the toxicities of patulin and patulin adducts formed with cysteine.

The toxicities of patulin and of the patulin adducts formed with cysteine were compared using the mutation-sensitive strain Escherichia coli W3110 thy polA1 and its polA1+ revertant. The acute toxicities of patulin and of the adduct mixture were also compared using NMRI mice. The adduct mixture was shown by thin-layer chromatography to consist of one ninhydrin-positive, one ninhydrin- and MBTH (3-methyl-2-benzothiazolinone hydrazone)-positive, three MBTH-positive, and two ninhydrin- and MBTH-negative components. The results showed that patulin was over 100 times more toxic to E. coli than the adduct complex. Neither patulin nor the adduct mixture was found to induce the repair effect in E. coli. In the mouse feeding tests, the oral 50% lethal dose for patulin was 29 mg/kg, while that of the adduct mixture was greater than 2,370 mg/kg.

Animals↗
PubMed1979

[Hygienic significance of patulin in food. 2. Occurrence of patulin in fruit and vegetables].

The analyses of more than 200 samples of various foods of plant origin showed that patulin was contained in 36% of the fresh and canned fruits infested with mould, and in 7% of the vegetables. Besides apples, pears, plums, peaches and tomatoes contained also patulin. In organoleptically impeccable fruit juices, the contamination rates were 40% (for apple juice) and 16% (for the other juices, such as sour cherry, currant, sea buckthorn juices). The patulin content varied from 20 to 200 microgram/l, the mean value being 80 microgram/l. It ranged from 0.1 to 5 microgram/g in apples and sterile apple preserves. The authors discuss the hygienic-toxicologic significance of these findings, and suggest to include patulin in the examination of foods for mycotoxins, stipulating a permissible value.

Food Analysis↗
PubMed1976

Teratogenicity of patulin and patulin adducts formed with cysteine.

The mean lethal dose of patulin for the chicken embryo injected in the air cell before incubation was determined to be 68.7 mug and that for the 4-day-old embryo was 2.35 mug. Both patulin (1 to 2 mug/egg) and the reaction mixture between patulin and cysteine (15 to 150 mug of patulin equivalents) were teratogenic to the chicken embryo. At least two ninhydrin-negative and four ninhydrin-positive products were formed during the latter reaction. Our explanation of the reaction mechanism remains to be elaborated.

Animals↗
PubMed1979

[Hygienic significance of patulin in foods. 1. Analytical detection of patulin].

The authors describe a thin-layer chromatographic method for determining patulin in fruit and vegetable products which is suited for routine work in hygiene practice. The samples are extracted with ethyl acetate, and the extracts are purified on a Florisil column. Separation is performed by means of a one-dimensional technique, using toluene/ehtyl acetate/formic acid (5 + 4 + 1), or, in the presence of interfering contaminants, by means of a two-dimensional technique, using benzene/methanol/glacial acetic acid (90 + 5 + 5) for the first run, and toluene/ethyl acetate/formic acid (5 + 4 + 1) for the second run. Patulin is detected by spraying with a benzidine solution, after chlorination. The limits of detection are 5 microgram/l of juice and 5 microgram/kg of fruit or vegetable. Derivatization with acetic anhydride/pyridine is used for corroborating the results obtained. The significance of 5-hydroxymethylfurfural as an interfering substance in apple juices is discussed.

Chromatography, Thin Layer↗
PubMed1977

[Determination of patulin in foodstuffs. Part I: Determination of patulin in apple juice (author's transl)].

For the determination of Patulin in apple juice a method of analysis was developed permitting the detection of 40 microng Patulin/kg apple juice. With additions between 120--200 microng Patulin/kg the recovery rates lie between 82 and 90%. After a pre-purification of the crude extract by liquid-liquid extraction and column-chromatography the Patulin is determined thinlayer chromatographically by reflectance measurement at 273 nm.

Beverages↗
PubMed1977

[Determination of patulin in foodstuffs Part II: Determination of patulin in tomatoes, pears, apples cucumbers and plums (author's transl)].

An analytical method for the determination of Patulin in tomatoes, pears, apples, cucumbers and plums is described. The determination limit of the method is 40 mug Patulin/kg. With additions between 100-500 mug Patulin/kg the recovery rates lie between 86--95%. After a pre-purification of the crude extract by column chromatography and liquid-liquid extraction the Patulin is determined thin-layer chromatographically by reflectance measurement at 273 nm.

Fruit↗
PubMed2006

Evaluation of the reproductive toxicity of patulin in growing male rats.

Patulin is a mycotoxin produced by several Penicillium, Aspergillus and Byssachlamys species. Patulin can be produced on different food products including fruits, grains, cheese, cured meats, but in natural situations patulin is exclusively found in apple and apple products. Patulin, at dose of 0.1mg/kg bw/day, was administered by gavage to the growing male rats aged 5-6 week for 60 or 90 days. At the end of the experiment, sperm counts and morphology were investigated. Also, effects of patulin on the epididymis, seminal vesicle and prostate tissues were examined histopathologically and morphologically. While sperm counts increased in patulin-treated rats for 60 days, sperm counts in patulin-treated rats for 90 days decreased compared to the corresponding control group. Patulin affected sperm morphology of growing male rats. Tail abnormalities like bent and/or coiled tails, and sticking of sperm tails were observed. A significant change was not determined in absolute and relative weights of the seminal vesicle and prostate of patulin-treated rats. While absolute cauda epididymal weights increased in rats treated with patulin for 60 days, absolute and relative cauda epididymal weights reduced in rats treated with patulin for 90 days. In histologic examination, some histopathological changes were observed in the epididymis and prostate tissues of rats in patulin treatment groups.

Administration, Oral↗
PubMed2003

Apple quality, storage, and washing treatments affect patulin levels in apple cider.

Patulin is a mycotoxin produced primarily by Penicillium expansum, a mold responsible for rot in apples and other fruits. The growth of this fungus and the production of patulin are common in fruit that has been damaged. However, patulin can be detected in visibly sound fruit. The purpose of this project was to determine how apple quality, storage, and washing treatments affect patulin levels in apple cider. Patulin was not detected in cider pressed from fresh tree-picked apples (seven cultivars) but was found at levels of 40.2 to 374 microg/liter in cider pressed from four cultivars of fresh ground-harvested (dropped) apples. Patulin was not detected in cider pressed from culled tree-picked apples stored for 4 to 6 weeks at 0 to 2 degrees C but was found at levels of 0.97 to 64.0 microg/liter in cider pressed from unculled fruit stored under the same conditions. Cider from controlled-atmosphere-stored apples that were culled before pressing contained 0 to 15.1 microg of patulin per liter, while cider made from unculled fruit contained 59.9 to 120.5 microg of patulin per liter. The washing of ground-harvested apples before pressing reduced patulin levels in cider by 10 to 100%, depending on the initial patulin levels and the type of wash solution used. These results indicate that patulin is a good indicator of the quality of the apples used to manufacture cider. The avoidance of ground-harvested apples and the careful culling of apples before pressing are good methods for reducing patulin levels in cider.

Beverages↗
PubMed1985

Toxicity of the mycotoxin patulin for rat alveolar macrophages.

Agricultural workers are exposed to a variety of organic dusts containing fungi and their secondary metabolites. Patulin, a polyketide lactone mycotoxin produced by several common species of Aspergillus and Penicillium, is found in corn silage. Patulin is toxic in experimental animals and has been reported to be mutagenic, teratogenic, and carcinogenic. The cytotoxicity of patulin was studied in rat alveolar macrophages in vitro. The effects of patulin on membrane integrity were studied by measuring cell volume changes and release of 51Cr. There was a significant release of 51Cr after 1 hr exposure to submillimolar concentrations of patulin. Similarly, there was a significant decrease in ATP in cell cultures exposed to 0.5 mM patulin for 15 min and in cultures exposed to 0.05 mM patulin for 2 hr. There was a significant increase in mean cell volume after 2 hr exposure to 1.0 mM patulin but not after a 1 hr exposure. The effects of patulin on protein and RNA synthesis were studied by monitoring the incorporation of [3H]leucine and [3H]uridine, respectively. Inhibitions of protein and of RNA synthesis were both dose and time dependent. Protein synthesis was the most sensitive cellular parameter studied, with 50% inhibition after 1 hr at ca. 0.002 mM patulin. The data demonstrate that patulin is cytotoxic for rat alveolar macrophages in vitro.

Adenosine Triphosphate↗
PubMed2005

Studies on the affinity chromatography purification of anti-patulin polyclonal antibodies by enzyme linked immunosorbent assay and electrophoresis.

Patulin is a mycotoxin produced by fungal species that frequently grow on fruit and vegetables. It presents risks, particularly for children consuming compotes and fruit juices. Thus, it is important to have methods such as immunoassays to screen a large number of samples. In the relevant literature, previous studies on the production of antibodies against patulin derivatives described qualitative tests for a patulin derivative or showed slight responses. The present study reinvestigated the production of polyclonal antibodies against patulin and their purification since crude antiserum could react non-specifically in immunoassays. Patulin-hemiglutarate was synthesized and conjugated to bovine serum albumin as the immunogen for the immunization of five New Zealand white rabbits. The immunoglobulin G (IgG) fraction was isolated twice by affinity chromatography using Sepharose-LS gel and recombinant G-protein. Classic affinity chromatography using Sepharose-LS gel was unable to eliminate serum albumin from the IgG fraction and the use of recombinant G-protein was efficient to isolate the purified IgG. Titres and specificity were determined by indirect competitive enzyme-linked immunosorbent assay. Patulin-hemiglutarate-ovalbumin gave complete displacement, while patulin displaced 30% of bound antibodies. Thus, a fraction of the antibodies are specific for free patulin. The non-specific binding increased with patulin concentrations. The electrophilic properties of patulin might also induce intermolecular cross-links in vitro that hinder the possibility of responses displacement when free patulin is used.

Animals↗
PubMed2002

The mycotoxin patulin alters the barrier function of the intestinal epithelium: mechanism of action of the toxin and protective effects of glutathione.

Patulin is a mycotoxin mainly found in apple and apple products. In addition to being toxic for animals, mutagenic, carcinogenic and teratogenic, patulin induces intestinal injuries, including epithelial cell degeneration, inflammation, ulceration, and hemorrhages. In a study of the cellular mechanisms associated with the intestinal toxicity of patulin, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14) were exposed to the mycotoxin. Micromolar concentrations of patulin were found to induce a rapid and dramatic decrease of transepithelial resistance (TER) in both cell lines without major signs of toxicity as assessed by the LDH release assay. Since TER reflects the organization of tight junctions, these data indicate that patulin affected the barrier function of the intestinal epithelium. The inhibitory effect of patulin on TER was closely associated with its reactivity for SH groups: (i) cysteine and glutathione prevented the cells from patulin injury; (ii) patulin toxicity was potentiated by buthionine sulfoximine, a specific glutathione-depleting agent; (iii) treatment of the cells with N-ethylmaleimide, a compound known to react with SH groups, resulted in a marked decrease of TER. Moreover, the inhibitory effect of patulin on TER was mimicked and potentiated by phenylarsine oxide, a specific inhibitor of protein tyrosine phosphatase (PTP). This cellular enzyme is a key regulator of intestinal epithelial barrier function. The active site of PTP contains a cysteine residue (Cys215) that is essential for phosphatase activity. Sulfhydryl-reacting compounds such as acetaldehyde decrease TER through covalent modification of Cys215 of PTP. We propose that the toxicity of patulin for intestinal cells involves, among other potential mechanisms, an inactivation of the active site of PTP.

Antidotes↗