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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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Comparative toxicity of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate on the ribosome, determined by an in vitro transcription/translation assay with rabbit reticulocyte lysate. Error bars denote the analytical standard deviation of three independent determinations.
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toxins-07-04706-f003: Comparative toxicity of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate on the ribosome, determined by an in vitro transcription/translation assay with rabbit reticulocyte lysate. Error bars denote the analytical standard deviation of three independent determinations.

Mentions: The toxicity of DON, DON-3-sulfate, and DON-15-sulfate on the ribosome had recently been assessed in in vitro transcription/translation assays with wheat germ extract [31]. In short, DON-3-sulfate did not show any toxicity in the investigated concentration range, whereas DON-15-sulfate was ca. 44 times less toxic than DON. To compare the toxicities of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate, in vitro transcription/translation assays were performed with mammalian ribosomes (Figure 3). While 50% reduction of in vitro translation by rabbit reticulocyte lysate was obtained at 0.6 μM DON, the IC50 value of DOM was 410 μM. DOM-3-sulfate and DOM-15-sulfate did not significantly inhibit in vitro translation at concentrations up to 100 μM. The translation efficiency was still 81% and 75% at 500 μM DOM-3-sulfate and DOM-15-sulfate, respectively. Inhibition of translation was not significantly different for DOM-3-sulfate and DOM-15-sulfate at substrate concentrations up to 250 μM. At a concentration of 500 μM, differences in translation were minor, but significant. Based on IC20 values for DON (0.25 μM), DOM (122 μM), DOM-3-sulfate (490 μM), and DOM-15-sulfate (420 μM), DOM-3-sulfate is less toxic than DOM by a factor of four and less toxic than DON by almost a factor of 2000. Similarly, DOM-15-sulfate shows lower toxicity on the ribosome than DOM by a factor of 3.4 and lower toxicity than DON by a factor of nearly 1700. Statistical analysis revealed significantly greater inhibition of translation by DOM compared to DOM-3-sulfate and DOM-15-sulfate from 250 μM onwards. These results confirm that de-epoxidation of DON leads to a less toxic metabolite and that sulfation of trichothecenes is, similar to glucosylation in plants, a detoxification mechanism.


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)

Comparative toxicity of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate on the ribosome, determined by an in vitro transcription/translation assay with rabbit reticulocyte lysate. Error bars denote the analytical standard deviation of three independent determinations.
© Copyright Policy
Related In: Results  -  Collection

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

toxins-07-04706-f003: Comparative toxicity of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate on the ribosome, determined by an in vitro transcription/translation assay with rabbit reticulocyte lysate. Error bars denote the analytical standard deviation of three independent determinations.
Mentions: The toxicity of DON, DON-3-sulfate, and DON-15-sulfate on the ribosome had recently been assessed in in vitro transcription/translation assays with wheat germ extract [31]. In short, DON-3-sulfate did not show any toxicity in the investigated concentration range, whereas DON-15-sulfate was ca. 44 times less toxic than DON. To compare the toxicities of DON, DOM, DOM-3-sulfate, and DOM-15-sulfate, in vitro transcription/translation assays were performed with mammalian ribosomes (Figure 3). While 50% reduction of in vitro translation by rabbit reticulocyte lysate was obtained at 0.6 μM DON, the IC50 value of DOM was 410 μM. DOM-3-sulfate and DOM-15-sulfate did not significantly inhibit in vitro translation at concentrations up to 100 μM. The translation efficiency was still 81% and 75% at 500 μM DOM-3-sulfate and DOM-15-sulfate, respectively. Inhibition of translation was not significantly different for DOM-3-sulfate and DOM-15-sulfate at substrate concentrations up to 250 μM. At a concentration of 500 μM, differences in translation were minor, but significant. Based on IC20 values for DON (0.25 μM), DOM (122 μM), DOM-3-sulfate (490 μM), and DOM-15-sulfate (420 μM), DOM-3-sulfate is less toxic than DOM by a factor of four and less toxic than DON by almost a factor of 2000. Similarly, DOM-15-sulfate shows lower toxicity on the ribosome than DOM by a factor of 3.4 and lower toxicity than DON by a factor of nearly 1700. Statistical analysis revealed significantly greater inhibition of translation by DOM compared to DOM-3-sulfate and DOM-15-sulfate from 250 μM onwards. These results confirm that de-epoxidation of DON leads to a less toxic metabolite and that sulfation of trichothecenes is, similar to glucosylation in plants, a detoxification mechanism.

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