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Insights into In Vivo Absolute Oral Bioavailability, Biotransformation, and Toxicokinetics of Zearalenone, α-Zearalenol, β-Zearalenol, Zearalenone-14-glucoside, and Zearalenone-14-sulfate in Pigs

Author:
Catteuw, Amelie, Broekaert, Nathan, De Baere, Siegrid, Lauwers, Marianne, Gasthuys, Elke, Huybrechts, Bart, Callebaut, Alfons, Ivanova, Lada, Uhlig, Silvio, De Boevre, Marthe, De Saeger, Sarah, Gehring, Ronette, Devreese, Mathias, Croubels, Siska
Source:
Journal of agricultural and food chemistry 2019 v.67 no.12 pp. 3448-3458
ISSN:
1520-5118
Subject:
bioavailability, biotransformation, excretion, hydrolysis, intravenous injection, metabolites, models, oral administration, pharmacokinetics, risk assessment, swine, toxicity, urine, zearalenone
Abstract:
The aim of this study was to determine the toxicokinetic characteristics of ZEN and its modified forms, α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S), including presystemic and systemic hydrolysis in pigs. Crossover pig trials were performed by means of intravenous and oral administration of ZEN and its modified forms. Systemic plasma concentrations of the administered toxins and their metabolites were quantified and further processed via tailor-made compartmental toxicokinetic models. Furthermore, portal plasma was analyzed to unravel the site of hydrolysis, and urine samples were analyzed to determine urinary excretion. Results demonstrate complete presystemic hydrolysis of ZEN14G and ZEN14S to ZEN and high oral bioavailability for all administered compounds, with further extensive first-pass glucuronidation. Conclusively, the modified-ZEN forms α-ZEL, β-ZEL, ZEN14G, and ZEN14S contribute to overall ZEN systemic toxicity in pigs and should be taken into account for risk assessment.
Agid:
6349719