Abstract

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration–time curve (AUC), 1.80 h·ng/mL; the apparent volume of distribution (VZ), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h·ng/mL; VZ, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats’ plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G.

Highlights

  • Zearalenone (ZEN), produced by the filamentous Fusarium fungi, is one of the most frequently occurring Fusarium mycotoxins [1,2]

  • The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism

  • High-resolution mass spectrometry (HRMS) and triple quadrupole coupled to mass spectrometry (MS/MS) have been widely used in various fields, including metabolism, environmental toxicity, and safety evaluation

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Summary

Introduction

Zearalenone (ZEN), produced by the filamentous Fusarium fungi, is one of the most frequently occurring Fusarium mycotoxins [1,2]. ZEN can react with estrogenic receptors, exhibiting estrogen-like activity [3]. The modified forms of mycotoxins have recently attracted considerable attention [4,5]. Food and feed contaminated with modified mycotoxins such as ZEN-14-glucoside (ZEN-14G) or deoxynivalenol-3-β-D-glucoside (DON-3G) could result in potential underestimation of the exposure [4,6]. The European Commission stated that it is appropriate to evaluate the exposure to modified forms of various toxins in addition to the parent compounds [7], since the modified forms might be hydrolyzed into the parent toxins, exerting toxicity [8,9]. The estrogenic potency of ZEN-14G is comparable to that of ZEN [7]

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