engleski

Deoxynivalenol metabolism: recent in vivo and in vitro studies in human and animal species

Deoxynivalenol (DON, vomitoxin) is a frequent food contaminant and one of the most abundant mycotoxins worldwide. Upon absorption, the major portion of the toxin is excreted by humans and animal species as glucuronide conjugate. Knowledge about the conjugative metabolism of xenobiotics such as DON is crucial for estimation of toxic effects and intrinsic clearance in humans but also for estimating the susceptibility of animals fed with contaminated feed. However, while limited in vivo data on human DON metabolism was published recently, consistent in vitro data on glucuronidation is lacking. In this work, we present a mass balance experiment in which a volunteer ingested defined food portions, previously analysed for their mycotoxin concentration levels. By this the human DON in vivo metabolism was preliminarily investigated and the urinary excretion rate and glucuronidation pattern was examined. Besides DON-l5-glucuronide and DON-3-glucuronide, which have been described before, a third DON-glucuronide was identified. The same conjugate was also observed in highly naturally contaminated urine samples obtained from pregnant Croatian women and in a microsomal in vitro assay. Consequently, the corresponding chromatographical peak was compared with a NMR confirmed reference standard of DON-8-glucuronide which was recently synthesized using rat liver microsomes. Interestingly, neither the third glucuronide in the naturally contaminated human urine samples nor the one observed in the microsomal assay was consistent with the DON-8- glucuronide standard. This opens up for the formation of DON-7-glucuronide and a total of four potentially produced DON conjugates. One of the above mentioned in vitro experiments was designed to investigate the role of hepatic metabolism in human and several animal species, namely rat, bovine, porcine, trout and carp. Results indicate extensive hepatic glucuronidation and point at differences in the formation of up to four different mono-O-glucuronides with significant interspecies differences.

deoxynivalenol; metabolism; deoxynivalenol glucuronides; LC-MS/MS

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