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1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.
Anne-Margarethe Enge; Florian Kaltner; Christoph Gottschalk; Albert Braeuning; Stefanie Hessel-Pras. Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells. International Journal of Molecular Sciences 2021, 22, 3821 .
AMA StyleAnne-Margarethe Enge, Florian Kaltner, Christoph Gottschalk, Albert Braeuning, Stefanie Hessel-Pras. Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells. International Journal of Molecular Sciences. 2021; 22 (8):3821.
Chicago/Turabian StyleAnne-Margarethe Enge; Florian Kaltner; Christoph Gottschalk; Albert Braeuning; Stefanie Hessel-Pras. 2021. "Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells." International Journal of Molecular Sciences 22, no. 8: 3821.
Pyrrolizidine alkaloids (PA) and PA-N-oxides (PANO) are a group of more than 660 secondary plant metabolites with hepatotoxic, carcinogenic and mutagenic effects in animals and humans. The phytotoxins can enter the food chain by transfer of PA/PANO between plants via the soil, unintended co-harvesting of PA/PANO-producing weeds, as well as by honeybees collecting pollen and nectar of these plants. Thus, bee- and plant-based products, e.g. (herbal) teas, spices and culinary herbs were identified to be a main source of consumers’ exposure to PA/PANO. Consequently, food supplements based on those ingredients may as well be contaminated with PA/PANO, but so far there are only very few studies available on this topic. Therefore, the current study investigated 50 herbal and bee product-based food supplements available in German retail pharmacies, drugstores, and online on the occurrence of 44 PA/PANO. In total, 19 samples contained PA/PANO with sum contents ranging from 0.1 to 105.1 ng/g in solid samples and from 0.03 to 2.20 ng/mL in liquid preparations. Considering the recommended daily consumption, the sum contents were of no or little concern for the health risk of adults, whereas in case of children the contents of singular samples could significantly contribute to the overall PA/PANO exposure.
Florian Kaltner; Verena Kukula; Christoph Gottschalk. Screening of food supplements for toxic pyrrolizidine alkaloids. Journal of Consumer Protection and Food Safety 2020, 15, 237 -243.
AMA StyleFlorian Kaltner, Verena Kukula, Christoph Gottschalk. Screening of food supplements for toxic pyrrolizidine alkaloids. Journal of Consumer Protection and Food Safety. 2020; 15 (3):237-243.
Chicago/Turabian StyleFlorian Kaltner; Verena Kukula; Christoph Gottschalk. 2020. "Screening of food supplements for toxic pyrrolizidine alkaloids." Journal of Consumer Protection and Food Safety 15, no. 3: 237-243.
Pyrrolizidine alkaloids (PA) and PA N-oxides (PANO) are secondary plant metabolites exhibiting genotoxic and carcinogenic properties. Apart from the roots and leaves, PA/PANO are particularly present in pollen and nectar. Therefore, the spread of Jacobaea vulgaris in certain regions of northern Germany has an impact on the safety of honey produced in that region. In this study, raw honey samples (n = 437) were collected from usually three individual beehives per site (n = 73) in the district of Ostholstein and analyzed for 25 PA/PANO. The results reveal mean levels of 8.4, 1.5, and 72.6 µg/kg and maximum levels of 111, 59.4, and 3313 µg/kg, depending on the season (summer 2015 and spring/summer 2016, respectively). As far as individual data are concerned, sites near areas with J. vulgaris growth did not necessarily result in high PA/PANO values. Furthermore, intra-site investigations revealed remarkable differences in PA/PANO levels of raw honey collected by different bee colonies at the same site. Consumption of these regionally produced honeys entails an increased exposure to PA/PANO, especially in children and high consumers. Margin of exposure values of <10,000 and an exceedance of the health-based guidance value highlight that regionally produced and marketed honey must be considered with care for a proper risk assessment and risk management.
Christoph Gottschalk; Florian Kaltner; Matthias Zimmermann; Rainer Korten; Oliver Morris; Karin Schwaiger; Manfred Gareis. Spread of Jacobaea vulgaris and Occurrence of Pyrrolizidine Alkaloids in Regionally Produced Honeys from Northern Germany: Inter- and Intra-Site Variations and Risk Assessment for Special Consumer Groups. Toxins 2020, 12, 441 .
AMA StyleChristoph Gottschalk, Florian Kaltner, Matthias Zimmermann, Rainer Korten, Oliver Morris, Karin Schwaiger, Manfred Gareis. Spread of Jacobaea vulgaris and Occurrence of Pyrrolizidine Alkaloids in Regionally Produced Honeys from Northern Germany: Inter- and Intra-Site Variations and Risk Assessment for Special Consumer Groups. Toxins. 2020; 12 (7):441.
Chicago/Turabian StyleChristoph Gottschalk; Florian Kaltner; Matthias Zimmermann; Rainer Korten; Oliver Morris; Karin Schwaiger; Manfred Gareis. 2020. "Spread of Jacobaea vulgaris and Occurrence of Pyrrolizidine Alkaloids in Regionally Produced Honeys from Northern Germany: Inter- and Intra-Site Variations and Risk Assessment for Special Consumer Groups." Toxins 12, no. 7: 441.
Pyrrolizidine alkaloids (PA) and their N-oxides (PANO) are a group of toxic secondary plant metabolites occurring predominantly as contaminants in (herbal) teas, honeys and food supplements, as well as in spices and culinary herbs. Depending on the botanical origin of the contaminating plant, the pattern of PA/PANO can strongly vary within a sample. The current study aimed to broaden the existing data on the occurrence of PA/PANO in spices and culinary herbs. For this, 305 authentic samples covering 15 different matrices mainly harvested in 2016 or 2017 and originating from 36 countries were investigated for the presence of 44 PA/PANO. Fifty-eight percent of the samples contained at least one PA/PANO. The average sum content over all samples was 323 µg/kg (median of 0.9 µg/kg, 95% percentile of 665 µg/kg). The highest amount of 24.6 mg/kg was detected in an oregano sample. Additionally, conspicuous analyte patterns were discovered in samples from similar cultivation regions, indicating related botanical sources of PA/PANO contaminations. Particularly, oregano and cumin from Turkey often contained high amounts of PA/PANO. The results were used to assess the acute and chronic health risks related to PA/PANO intake via spices and culinary herbs, indicating a potential health risk in particular for adults and children with high consumption or when considering worst-case contamination scenarios of a sum content of 5500 µg/kg.
Florian Kaltner; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. Occurrence and Risk Assessment of Pyrrolizidine Alkaloids in Spices and Culinary Herbs from Various Geographical Origins. Toxins 2020, 12, 155 .
AMA StyleFlorian Kaltner, Michael Rychlik, Manfred Gareis, Christoph Gottschalk. Occurrence and Risk Assessment of Pyrrolizidine Alkaloids in Spices and Culinary Herbs from Various Geographical Origins. Toxins. 2020; 12 (3):155.
Chicago/Turabian StyleFlorian Kaltner; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. 2020. "Occurrence and Risk Assessment of Pyrrolizidine Alkaloids in Spices and Culinary Herbs from Various Geographical Origins." Toxins 12, no. 3: 155.
Pyrrolizidine alkaloids (PA) and PA-N-oxides (PANO) are a large group of secondary plant metabolites comprising more than 660 compounds. Exhibiting geno- and hepatotoxic properties, they are responsible for multiple cases of food and feed poisoning over the last 100 years. For food and feed safety reasons, relevant PA/PANO should be monitored extensively in the main sources of PA/PANO intake. In this study, a sensitive analytical method was developed for detecting a broad range of 44 commercially available PA/PANO compounds, and in-house validation procedures were performed for several (herbal) teas. Various extraction solvents and procedures, as well as solid phase extraction materials for sample clean-up and analyte concentration, were tested to establish the methods’ efficiency and effectiveness. Chromatographic conditions were optimised to obtain the best possible separation of isomers for the 44 PA/PANO analytes. The final method was proven very sensitive and accurate, with detection limits ranging from 0.1 to 7.0 μg/kg and precisions between 0.7 and 16.1%. For 40 of the analytes, the recovery rates ranged from 60.7 to 128.8%. The applicability and trueness of the method were examined by analysing tea samples from a local supermarket and comparing them to a reference material. At least one PA/PANO analyte was detected in 17 of the 18 samples under investigation, and the sum contents of the samples ranged from 0.1 to 47.9 μg/kg. Knowledge of the PA/PANO composition in a sample can be used to indicate the botanical origin of the impurity and, thus, the geographical region of cultivation.
Florian Kaltner; Benedikt Stiglbauer; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. Development of a sensitive analytical method for determining 44 pyrrolizidine alkaloids in teas and herbal teas via LC-ESI-MS/MS. Analytical and Bioanalytical Chemistry 2019, 411, 7233 -7249.
AMA StyleFlorian Kaltner, Benedikt Stiglbauer, Michael Rychlik, Manfred Gareis, Christoph Gottschalk. Development of a sensitive analytical method for determining 44 pyrrolizidine alkaloids in teas and herbal teas via LC-ESI-MS/MS. Analytical and Bioanalytical Chemistry. 2019; 411 (27):7233-7249.
Chicago/Turabian StyleFlorian Kaltner; Benedikt Stiglbauer; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. 2019. "Development of a sensitive analytical method for determining 44 pyrrolizidine alkaloids in teas and herbal teas via LC-ESI-MS/MS." Analytical and Bioanalytical Chemistry 411, no. 27: 7233-7249.
The fungus Stachybotrys (S.) chartarum was isolated from culinary herbs, damp building materials, and improperly stored animal forage. Two distinct chemotypes of the fungus were described that produced either high-cytotoxic macrocyclic trichothecenes (S type) or low-cytotoxic atranones (A type). Recently, two distinct gene clusters were described that were found to be necessary for the biosynthesis of either macrocyclic trichothecenes (21 SAT (Satratoxin) genes) or atranones (14 ATR (Atranone) genes). In the current study, PCR primers were designed to detect SAT and ATR genes in 19 S. chartarum chemotype S and eight S. chartarum chemotype A strains. Our analysis revealed the existence of three different genotypes: satratoxin-producing strains that harbored all SAT genes but lacked the ATR gene cluster (genotype S), non-satratoxin-producing strains that possessed the ATR genes but lacked SAT genes (genotype A), and a hitherto undescribed hybrid genotype among non-satratoxin-producing strains that harbored all ATR genes and an incomplete set of SAT genes (genotype H). In order to improve the discrimination of genotypes, a triplex PCR assay was developed and applied for the analysis of S. chartarum and S. chlorohalonata cultures. The results show that genes for macrocyclic trichothecenes and atranones are not mutually exclusive in S. chartarum. Correlation of the new genotype-based concept with mycotoxin production data shows also that macrocyclic trichothecenes are exclusively produced by S. chartarum genotype S strains.
Sebastian Ulrich; Ludwig Niessen; Julia Ekruth; Cornelius Schäfer; Florian Kaltner; Christoph Gottschalk. Truncated satratoxin gene clusters in selected isolates of the atranone chemotype of Stachybotrys chartarum (Ehrenb.) S. Hughes. Mycotoxin Research 2019, 36, 83 -91.
AMA StyleSebastian Ulrich, Ludwig Niessen, Julia Ekruth, Cornelius Schäfer, Florian Kaltner, Christoph Gottschalk. Truncated satratoxin gene clusters in selected isolates of the atranone chemotype of Stachybotrys chartarum (Ehrenb.) S. Hughes. Mycotoxin Research. 2019; 36 (1):83-91.
Chicago/Turabian StyleSebastian Ulrich; Ludwig Niessen; Julia Ekruth; Cornelius Schäfer; Florian Kaltner; Christoph Gottschalk. 2019. "Truncated satratoxin gene clusters in selected isolates of the atranone chemotype of Stachybotrys chartarum (Ehrenb.) S. Hughes." Mycotoxin Research 36, no. 1: 83-91.
The contamination of honey with hepatotoxic pyrrolizidine alkaloids (PAs) is a well-known hazard for food safety. While management strategies and controls of the honey industry aim to reduce the PA levels, uncertainties remain with regard to the safety of regionally produced and marketed honey. In addition, a previous study showed large differences of results obtained after various periods of storage and apparent differences between the analytical results of different laboratories. Therefore, this study aimed at examining these uncertainties by monitoring the impact of storage on the PA and PA N-oxide (PANO) content of two freshly harvested honeys and on possible demixing effects caused by pollen settling. Additionally, three analytical approaches – target analysis with matrix-matched calibration or standard addition and a sum parameter method – were applied for a comparative analysis of 20 honeys harvested in summer 2016. All samples originated from Schleswig-Holstein in Northern Germany where the PA plant Jacobaea vulgaris is currently observed on a massive scale. The results of the time series analyses showed that PANO levels markedly decreased within a few weeks and practically reached the LOD 16 weeks after harvest. Tertiary PAs, by contrast, remained stable and did not increase as a consequence of PANO decrease. The experiments on a putative demixing, which may result in a heterogeneous distribution of PAs/PANOs, revealed that there was no such effect during storage of up to 12 weeks. A comparison of the PA/PANO levels obtained by different analytical approaches showed that in some cases the sum parameter method yielded much higher levels than the target approaches, whereas in other cases, the target analysis with standard addition found higher levels than the other two methods. In summary, the results of this study highlight uncertainties regarding the validity and comparability of analytical results and consequently regarding health risk assessment.
Christoph Gottschalk; Aiko Huckauf; Arne Dübecke; Florian Kaltner; Matthias Zimmermann; Ines Rahaus; Till Beuerle. Uncertainties in the determination of pyrrolizidine alkaloid levels in naturally contaminated honeys and comparison of results obtained by different analytical approaches. Food Additives & Contaminants: Part A 2018, 35, 1366 -1383.
AMA StyleChristoph Gottschalk, Aiko Huckauf, Arne Dübecke, Florian Kaltner, Matthias Zimmermann, Ines Rahaus, Till Beuerle. Uncertainties in the determination of pyrrolizidine alkaloid levels in naturally contaminated honeys and comparison of results obtained by different analytical approaches. Food Additives & Contaminants: Part A. 2018; 35 (7):1366-1383.
Chicago/Turabian StyleChristoph Gottschalk; Aiko Huckauf; Arne Dübecke; Florian Kaltner; Matthias Zimmermann; Ines Rahaus; Till Beuerle. 2018. "Uncertainties in the determination of pyrrolizidine alkaloid levels in naturally contaminated honeys and comparison of results obtained by different analytical approaches." Food Additives & Contaminants: Part A 35, no. 7: 1366-1383.
1,2-dehydropyrrolizidine alkaloids (PA) and PA-N-oxides (PANO) are phytotoxins, which presumably occur in more than 6000 plant species worldwide. Plants containing PA/PANO are responsible for various food and feed poisonings recorded for decades. Main reasons of exposition of consumers and livestock are contaminations of food and animal feed with parts, seeds, pollen or nectar of PA containing plants. Concerning stability, effects of processing on PA were mainly investigated in the past. The current study examined the behavior of PA/PANO in unprocessed matrices peppermint tea, hay and honey during storage. Blank samples were fortified with PA/PANO or contaminated with blueweed (Echium vulgare) and ragwort (Senecio jacobaea) and stored for 182 d. The time-series analysis using liquid chromatography tandem-mass spectrometry (LC-MS/MS) confirmed that all 25 analyzed PA/PANO compounds remained stable in herbal samples. However, the results showed a very fast decrease of PANO in honey samples within hours. These results were discussed with respect to potential consequences for health risk assessment.
Florian Kaltner; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. Influence of Storage on the Stability of Toxic Pyrrolizidine Alkaloids and Their N-Oxides in Peppermint Tea, Hay, and Honey. Journal of Agricultural and Food Chemistry 2018, 66, 5221 -5228.
AMA StyleFlorian Kaltner, Michael Rychlik, Manfred Gareis, Christoph Gottschalk. Influence of Storage on the Stability of Toxic Pyrrolizidine Alkaloids and Their N-Oxides in Peppermint Tea, Hay, and Honey. Journal of Agricultural and Food Chemistry. 2018; 66 (20):5221-5228.
Chicago/Turabian StyleFlorian Kaltner; Michael Rychlik; Manfred Gareis; Christoph Gottschalk. 2018. "Influence of Storage on the Stability of Toxic Pyrrolizidine Alkaloids and Their N-Oxides in Peppermint Tea, Hay, and Honey." Journal of Agricultural and Food Chemistry 66, no. 20: 5221-5228.
Pyrrolizidinalkaloide stehen im Verdacht, Krebs zu erzeugen, und sind immer wieder in Tees oder Honig nachweisbar. Die problematische Analytik der Substanzen und ihr zum Teil ungeklärtes Verhalten in Lebens- und Futtermitteln machen eine Risikoeinschätzung schwierig.
Florian Kaltner; Christoph Gottschalk; Manfred Gareis. Pflanzeninhaltsstoffe als Kontaminanten in der Lebensmittelkette. Nachrichten aus der Chemie 2018, 66, 109 -113.
AMA StyleFlorian Kaltner, Christoph Gottschalk, Manfred Gareis. Pflanzeninhaltsstoffe als Kontaminanten in der Lebensmittelkette. Nachrichten aus der Chemie. 2018; 66 (2):109-113.
Chicago/Turabian StyleFlorian Kaltner; Christoph Gottschalk; Manfred Gareis. 2018. "Pflanzeninhaltsstoffe als Kontaminanten in der Lebensmittelkette." Nachrichten aus der Chemie 66, no. 2: 109-113.
Fumonisins, a type of mycotoxins produced by Fusarium species, can cause fatal diseases in animals and humans. Therefore, regulatory limits for food and feed were established in many countries. Herein, a sensitive, valid, cost-effective, and easily transferable analytical method for quantitative determination of the relevant fumonisins B1 (FB1) and B2 (FB2) in corn and corn products was developed. The final method is based on reversed-phase high-performance liquid chromatography with fluorescence detection (RP-HPLC-FLD). Derivatization of analytes was simplified by establishing an automated precolumn derivatization method by using an autosampler. Strong anion exchange (SAX) cartridges were used instead of widespread immunoaffinity chromatography (IAC) approaches. Analytes and matrix signals were chromatographically separated in a total run time of 25 min by means of a C8 column and a gradient elution using methanol and phosphate buffer. The limits of detection (LODs) for FB1 and FB2 were 29.2 and 17.5 μg/kg, respectively. Obtained recoveries ranged from 79.4 to 94.5 % for FB1 and from 79.9 to 98.0 % for FB2. Positive confirmation of the developed method was achieved by participating in an interlaboratory proficiency testing. Nineteen samples of sweet corn and corn products were analyzed to demonstrate the applicability of the method.
Florian Kaltner; Corina Rampl; Michael Rychlik; Thomas Zimmermann; Alexander Rohe. Development and Validation of a Cost-Effective HPLC-FLD Method for Routine Analysis of Fumonisins B1 and B2 in Corn and Corn Products. Food Analytical Methods 2016, 10, 1349 -1358.
AMA StyleFlorian Kaltner, Corina Rampl, Michael Rychlik, Thomas Zimmermann, Alexander Rohe. Development and Validation of a Cost-Effective HPLC-FLD Method for Routine Analysis of Fumonisins B1 and B2 in Corn and Corn Products. Food Analytical Methods. 2016; 10 (5):1349-1358.
Chicago/Turabian StyleFlorian Kaltner; Corina Rampl; Michael Rychlik; Thomas Zimmermann; Alexander Rohe. 2016. "Development and Validation of a Cost-Effective HPLC-FLD Method for Routine Analysis of Fumonisins B1 and B2 in Corn and Corn Products." Food Analytical Methods 10, no. 5: 1349-1358.