Humans significantly metabolize and excrete the mycotoxin deoxynivalenol and its modified form deoxynivalenol-3-glucoside within 24 hours

Abstract

For the first time, a comprehensive human intervention study was conducted to unravel the urinary excretion profile and metabolism of the fungal metabolite deoxynivalenol (DON) and its modified form deoxynivalenol-3-glucoside (DON-3-glucoside). Twenty volunteers were restricted in consuming cereals and cereal-based foods for 4 days. At day 3, a single bolus of 1 µg/kg body weight of DON and a single bolus of 1 µg/kg body weight of DON-3-glucoside after a washing-out period of two months was administered, and a 24-h urine collection was performed. The urine was analysed for DON, DON-3-glucoside, 3-ADON, 15-ADON, deepoxy-deoxynivalenol (DOM-1), deoxynivalenol-3-glucuronide (DON-3-glucuronide) and deoxynivalenol-15-glucuronide (DON-15-glucuronide). The urinary biomarker-analysis revealed that DON and DON-3-glucoside were rapidly absorbed, distributed, metabolized and excreted. Sixty-four % of the administered DON and 58% of DON-3-glucoside was recovered in the urine collected within 24 h. DON-15-glucuronide was the most prominent urinary biomarker followed by free DON and DON-3-glucuronide. Moreover, correlations among the presence of DON-15-glucuronide and DON-3-glucuronide were observed (within 24 hours (r = 0.61)). The DOM-1 detected in the urine was higher after the DON-3-glucoside administration. The obtained results are imperative to construct a standardized method to estimate DON-intake by means of urinary biomarkers.

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

“…Regarding DON‐3‐glucoside, this toxin was almost completely converted to DON during rats’ digestion in the small intestine and in the gut (Berthiller et al., ; Nagl et al., ; Versilovskis et al., ). For this reason, DON‐3‐glucoside caused a similar DON excretion profile (Broekaert et al., ), and DON‐3‐glucoside was scarcely detected in the urine of humans (Vidal et al., ) and pigs (Nagl et al., ). On the contrary, no hydrolysis was observed after oral administration of DON‐3‐glucoside to chickens (Broekaert et al., ).…”

“…The study permitted to elucidate the excretion rate of DON (64%) and DON‐3‐glucoside (58%), as well as the fast excretion rate of DON, suggesting to collect at least 16‐hours urine to have a representative view on DON‐consumption. These results enabled to validate DON‐3‐glucuronide and DON‐15‐glucuronide as suitable DON and DON‐3‐glucoside biomarkers in urine (Vidal et al., ).…”

“…Also, DON‐sulfates (DON‐3‐sulfate and DON‐15‐sulfate) were identified in the urine from female rodents (Pestka et al., ). Concerning the gender difference, the DON excretion was higher in human females than human males due to a larger presence of glucuronidated forms (DON‐15‐glucuronide and DON‐3‐glucuronide) (Vidal et al., ). A rodent trial on DON exposure demonstrated that female animals had a higher UGT‐enzyme expression than males, which suggested a gender difference in the response to DON (Pestka et al., ).…”

“…A small DOM‐1 portion was identified in human urine after DON‐exposure (Vidal et al., ), although DOM‐1 was mainly excreted in pigs with the feces (Dänicke, Valenta, & Döll, ; Eriksen, Pettersson, Johnsen, & Lindberg, ). Nevertheless, due to the high absorption of DON by the small intestine, bacterial transformation of DON into DOM‐1 could only be possible when reaching the colon.…”

“…AFB1‐N7‐guanine adducts provided a more adequate measure of acute short term (24 to 48 hr)‐AFB1‐exposure (Groopman et al., ; Groopman, Dematos, Egner, Lovehunt, & Kensler, ; Groopman, Roebuck, & Kensler, ). AFB1‐lysine in plasma was validated as a reliable biomarker of chronic aflatoxin exposure using state‐of‐the‐art isotope dilution HRMS (McMillan, ), and DON‐glucuronides were validated in urine as a reliable biomarker of deoxynivalenol exposure (Vidal et al., ). However, up to date no more mycotoxin biomarkers of exposure were validated.…”