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Metabolism of deoxynivalenol and deepoxy-deoxynivalenol in broiler chickens, pullets, roosters and turkeys.

Schwartz-Zimmermann HE, Fruhmann P, Dänicke S, Wiesenberger G, Caha S, Weber J, Berthiller F - Toxins (Basel) (2015)

Bottom Line: Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry.In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60.This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine.

View Article: PubMed Central - PubMed

Affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, Tulln 3430, Austria. heidi.schwartz@boku.ac.at.

ABSTRACT
Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens and turkeys was developed and validated. To this end, DOM-3-sulfate was chemically synthesized and characterized by NMR and LC-HR-MS/MS measurements. Application of the method to excreta and chyme samples of four feeding trials with turkeys, chickens, pullets, and roosters confirmed DON-3-sulfate as the major DON metabolite in all poultry species studied. Analogously to DON-3-sulfate, DOM-3-sulfate was formed after oral administration of DOM both in turkeys and in chickens. In addition, pullets and roosters metabolized DON into DOM-3-sulfate. In vitro transcription/translation assays revealed DOM-3-sulfate to be 2000 times less toxic on the ribosome than DON. Biological recoveries of DON and DOM orally administered to broiler chickens, turkeys, and pullets were 74%-106% (chickens), 51%-72% (roosters), and 131%-151% (pullets). In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60. This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine.

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LC-MS/MS chromatogram of (a) a standard solution (30 ng/mL of DONS 1, DONS 2, DONS 3, DOMS 2, DON-3-sulfate, DOM-3-sulfate, DON, and DOM) and (b) of an excreta extract of a turkey fed a DOM-contaminated diet (1.6 mg/kg DOM and 0.2 mg/kg DON in feed).
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toxins-07-04706-f001: LC-MS/MS chromatogram of (a) a standard solution (30 ng/mL of DONS 1, DONS 2, DONS 3, DOMS 2, DON-3-sulfate, DOM-3-sulfate, DON, and DOM) and (b) of an excreta extract of a turkey fed a DOM-contaminated diet (1.6 mg/kg DOM and 0.2 mg/kg DON in feed).

Mentions: Similarly to production of DON-sulfates [31], synthesis of DOM-sulfates is a two-step reaction. In the first step, three protected intermediates were produced: 2,2,2-trichloroethyl-DOM-3-sulfate (71.0 mg, 29%), 2,2,2-trichloroethyl-DOM-15-sulfate (14.0 mg, 6%) and, as by-product, bis(2,2,2-trichloroethyl) DOM-3,15-disulfate (30.0 mg, 9%). These substances were recovered as white solid with an overall yield of 44%. NMR data of the protected intermediates are given in the electronic supplementary material; NMR spectra are shown in Figure S1. Deprotection of the intermediates and column chromatography with ammonium hydroxide as a mobile phase additive yielded 36.7 mg (67% of the protected intermediate) of DOM-3-sulfate, 5.3 mg (49%) of DOM-15-sulfate (both as ammonium salt), and 9.2 mg (45%) of the by-product DOM-3,15-disulfate (as diammonium salt). By using LC-HR-MS, the following molecular masses were obtained. DOM-3-sulfate: 360.0880 g/mol (exact molecular mass: 360.0879 g/mol); DOM-15-sulfate: 360.0879 g/mol (exact molecular mass: 360.0879 g/mol); DOM-3,15-disulfate: 440.0448 g/mol (exact molecular mass: 440.0447 g/mol). Results of NMR measurements are summarized in the electronic supplementary material; NMR and LC-HR-MS/MS spectra are given in Figures S2 and S3. The structures of DON- and DOM-sulfates are provided in Figure 1.


Metabolism of deoxynivalenol and deepoxy-deoxynivalenol in broiler chickens, pullets, roosters and turkeys.

Schwartz-Zimmermann HE, Fruhmann P, Dänicke S, Wiesenberger G, Caha S, Weber J, Berthiller F - Toxins (Basel) (2015)

LC-MS/MS chromatogram of (a) a standard solution (30 ng/mL of DONS 1, DONS 2, DONS 3, DOMS 2, DON-3-sulfate, DOM-3-sulfate, DON, and DOM) and (b) of an excreta extract of a turkey fed a DOM-contaminated diet (1.6 mg/kg DOM and 0.2 mg/kg DON in feed).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4663529&req=5

toxins-07-04706-f001: LC-MS/MS chromatogram of (a) a standard solution (30 ng/mL of DONS 1, DONS 2, DONS 3, DOMS 2, DON-3-sulfate, DOM-3-sulfate, DON, and DOM) and (b) of an excreta extract of a turkey fed a DOM-contaminated diet (1.6 mg/kg DOM and 0.2 mg/kg DON in feed).
Mentions: Similarly to production of DON-sulfates [31], synthesis of DOM-sulfates is a two-step reaction. In the first step, three protected intermediates were produced: 2,2,2-trichloroethyl-DOM-3-sulfate (71.0 mg, 29%), 2,2,2-trichloroethyl-DOM-15-sulfate (14.0 mg, 6%) and, as by-product, bis(2,2,2-trichloroethyl) DOM-3,15-disulfate (30.0 mg, 9%). These substances were recovered as white solid with an overall yield of 44%. NMR data of the protected intermediates are given in the electronic supplementary material; NMR spectra are shown in Figure S1. Deprotection of the intermediates and column chromatography with ammonium hydroxide as a mobile phase additive yielded 36.7 mg (67% of the protected intermediate) of DOM-3-sulfate, 5.3 mg (49%) of DOM-15-sulfate (both as ammonium salt), and 9.2 mg (45%) of the by-product DOM-3,15-disulfate (as diammonium salt). By using LC-HR-MS, the following molecular masses were obtained. DOM-3-sulfate: 360.0880 g/mol (exact molecular mass: 360.0879 g/mol); DOM-15-sulfate: 360.0879 g/mol (exact molecular mass: 360.0879 g/mol); DOM-3,15-disulfate: 440.0448 g/mol (exact molecular mass: 440.0447 g/mol). Results of NMR measurements are summarized in the electronic supplementary material; NMR and LC-HR-MS/MS spectra are given in Figures S2 and S3. The structures of DON- and DOM-sulfates are provided in Figure 1.

Bottom Line: Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry.In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60.This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine.

View Article: PubMed Central - PubMed

Affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, Tulln 3430, Austria. heidi.schwartz@boku.ac.at.

ABSTRACT
Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens and turkeys was developed and validated. To this end, DOM-3-sulfate was chemically synthesized and characterized by NMR and LC-HR-MS/MS measurements. Application of the method to excreta and chyme samples of four feeding trials with turkeys, chickens, pullets, and roosters confirmed DON-3-sulfate as the major DON metabolite in all poultry species studied. Analogously to DON-3-sulfate, DOM-3-sulfate was formed after oral administration of DOM both in turkeys and in chickens. In addition, pullets and roosters metabolized DON into DOM-3-sulfate. In vitro transcription/translation assays revealed DOM-3-sulfate to be 2000 times less toxic on the ribosome than DON. Biological recoveries of DON and DOM orally administered to broiler chickens, turkeys, and pullets were 74%-106% (chickens), 51%-72% (roosters), and 131%-151% (pullets). In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60. This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine.

Show MeSH
Related in: MedlinePlus