Naslov
Identification and toxicological characterization of deoxynivalenol-3-sulfate, a newly discovered metabolite of the mycotoxin deoxynivalenol in human urine

Autori
Warth, Benedikt ; Del Favero, Giorgia ; Puntscher, Hannes ; Jarolim, Katharina ; Pahlke, Gudrun ; Fruhmann, Philipp ; Šarkanj, Bojan ; Krska, Rudolf ; Schumacher, Reiner ; Adam, Gerhard ; Marko, Doris

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts 7th International symposium on recent advances in food analysis / Pulkrabova, Jana ; Tomaniova, Monika ; Nielen, Michel ; Hajšlova, Jana - Prag : University of Chemistry and Technology, Prague, 2015, 121-121

ISBN
978-80-7080-934-1

Skup
7th International symposium on recent advances in food analysis

Mjesto i datum
Prag, Češka Republika, 03.11.2015. - 06.11.2015

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
LC-MS/MS; bio-monitoring; phase II metabolism; biomarker of exposure; deoxynivalenol conjugate

Sažetak
The trichothecene mycotoxin deoxynivalenol (DON) is a frequent food contaminant and has been associated with gastroenteritis and primary symptoms such as nausea, diarrhea, and vomiting in humans. DON is extensively metabolized in plants, animals, and humans resulting in metabolites of diverse chemical and toxicological properties. In humans glucuronidation and de-epoxydation but not sulfation have been described as routes of DON conjugation/detoxification. In fact, no analytical methodology for the detection of the latter in human samples was available so far. Here, we report the development of a highly sensitive LC-MS/MS method for the quantification of DON-sulfates together with other relevant DON metabolites in human urine for advanced bio-monitoring purpose. Authentic DON-sulfate standards were chemically synthetized and confirmed by NMR. For sample preparation a ‘dilute and shoot’ approach was chosen. Despite urine dilution convenient limits of detection below 0.6 ng/mL were achieved for DON-3-sulfate and DON-15-sulfate. The developed method was applied to a set of urine samples obtained from pregnant women who were exposed to DON through their normal diet. Many of the samples have been previously shown to contain DON in concentrations up to 275 ng/mL and even higher concentrations of DON- glucuronides. Using the developed method we were able to detect DON-3-sulfate in 29 out of 40 urine samples (72%). The maximum and median concentration of DON-3-sulfate was 56 ng/mL and 1.5 ng/mL, respectively contributing to about 3-4% of the total DON content in the tested samples (i.e. sum of DON, DON-3-glucuronide, DON-15-glucuronide, and DON-3-sulfate). Interestingly, no DON-15-sulfate was detected in any sample. Though the absolute concentrations of DON-3- sulfate were lower than those of DON- glucuronides, the detection of this novel metabolic pathway in humans opens up for new research questions. In fact, the contribution of sulfate metabolites to the overall toxicity of DON remains to be clarified. Therefore, in vitro experiments were pre this novel human excretion mechanism warrants more detailed investigation. Therefore, in vitro experiments were performed for a first toxicological characterization of DON-sulfates in human HT-29 colon cells. Several assays were carried out focusing on cellular activation of the Nrf2/ARE pathway. The overall results of these toxicological experiments suggested that DON-3- sulfate might not be considered as a human detoxification mechanism. In view of the first identification of this metabolite in human urine these results suggest a more detailed investigation of this newly discovered conjugate of the Fusarium toxin DON in human.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Prehrambena tehnologija

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