Aromatic hydroxylation is a major metabolic pathway of the mycotoxin zearalenone in vitro

Pfeiffer E, Hildebrand A, Damm G, Rapp A, Cramer B, Humpf HU, Metzler M

Forschungsartikel (Zeitschrift)

Zusammenfassung

Zearalenone (ZEN) is a common mycotoxin, for which only reductive metabolites have been identified so far. We now report that ZEN is extensively monohydroxylated by microsomes from human liver in vitro. Two of the major oxidative metabolites arise through aromatic hydroxylation and are catechols. Their chemical structures have been unambiguously determined by using deuterium-labeled ZEN and by comparison with authentic reference compounds. Moreover, both catechol metabolites of ZEN were substrates of the enzyme catechol-O-methyl transferase. One of the monomethyl ethers represented the major metabolite when ZEN was incubated with rat liver slices, thus demonstrating that catechol formation also takes place under in vivo-like conditions. Out of ten major human cytochrome P450 (hCYP) isoforms only hCYPIA2 was able to hydroxylate ZEN to its catechols with high activity. Catechol formation represents a novel pathway in the metabolism of ZEN and may be of toxicological relevance.

Details zur Publikation

FachzeitschriftMolecular Nutrition and Food Research
Jahrgang / Bandnr. / Volume53
Ausgabe / Heftnr. / Issue9
Seitenbereich1123-1133
StatusVeröffentlicht
Veröffentlichungsjahr2009 (30.09.2009)
Sprache, in der die Publikation verfasst istEnglisch
DOI10.1002/mnfr.200800584
StichwörterAromatic hydroxylation Catechols Human liver Microsomes Zearalenone subcellular-fractions estrogenic mycotoxin species-differences zeranol liver

Autor*innen der Universität Münster

Cramer, Benedikt
Professur für Lebensmittelchemie (Prof. Humpf)
Humpf, Hans-Ulrich
Professur für Lebensmittelchemie (Prof. Humpf)