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Toxins 2017, 9(8), 240; doi:10.3390/toxins9080240

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

1
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
2
Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA
3
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA
4
Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, 3430 Tulln, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Sven Dänicke
Received: 29 June 2017 / Revised: 27 July 2017 / Accepted: 31 July 2017 / Published: 4 August 2017
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
View Full-Text   |   Download PDF [1104 KB, uploaded 4 August 2017]   |  

Abstract

Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses revealed that by 24 h, most DON and DON metabolites were excreted via urine (49–86%) as compared to feces (1.2–8.3%). Females excreted DON and its principal metabolites (DON-3-, DON-8,15 hemiketal-8-, and iso-DON-8-glucuronides) in urine more rapidly than males. Metabolite concentrations were typically 2 to 4 times higher in the livers and kidneys of males than females from 1 to 4 h after dosing. Trace levels of DON-3-sulfate and DON-15-sulfate were found in urine, liver and kidneys from females but not males. Fecal excretion of DON and DON sulfonates was approximately 2-fold greater in males than females. Finally, decreased DON clearance rates in males could not be explained by glucuronidation activities in liver and kidney microsomes. To summarize, increased sensitivity of male mice to DON’s toxic effects as compared to females corresponds to decreased ability to clear the toxin via urine but did not appear to result from differences in toxin metabolism. View Full-Text
Keywords: trichothecene; mycotoxin; metabolism; sex dependence trichothecene; mycotoxin; metabolism; sex dependence
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MDPI and ACS Style

Pestka, J.J.; Clark, E.S.; Schwartz-Zimmermann, H.E.; Berthiller, F. Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse. Toxins 2017, 9, 240.

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