title: Oxidative metabolism of the mycotoxins alternariol and alternariol-9-methyl ether in precision-cut rat liver slices in vitro.
abstract: METHODS
  Monohydroxylation of alternariol (AOH) and alternariol-9-methyl ether (AME) has previously been reported as a prominent metabolic route under cell-free conditions. This pathway gives rise to several catechol metabolites and may therefore be of toxicological relevance.
  
  
  RESULTS
  To clarify whether hydroxylation of AOH and AME occurs under in vivo-like conditions in the presence of conjugation reactions, the metabolism of the Alternaria toxins has now been studied in precision-cut rat liver slices. Four catechol metabolites of AOH and two of AME, together with several of their O-methylation products, as catalyzed by catechol-O-methyl transferase, were clearly identified after incubation of the liver slices with AOH and AME. These metabolites were predominantly present as conjugates with glucuronic acid and/or sulfate. In preliminary studies with bile duct-cannulated male rats dosed with AOH by gavage, the four monohydroxylated metabolites of AOH could also be demonstrated in the bile either as catechols or as O-methyl ethers.
  
  
  CONCLUSIONS
  These experiments clearly show that AOH and AME undergo catechol formation in vivo and warrant closer examination of the toxicological significance of this metabolic pathway.
authors.affiliation: Institute of Applied Biosciences, Chair of Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Burkhardt
authors.forename: Judith
authors.initials: J
authors.lastname: Wittenauer
authors.forename: Erika
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Ute M D
authors.initials: UM
authors.lastname: Schauer
authors.forename: Manfred
authors.initials: M
authors.lastname: Metzler
mesh_terms: D000818:Animals; D001652:Bile Ducts; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002396:Catechols / Q000378:metabolism; D002404:Catheterization; D020723:Glucuronic Acid / Q000378:metabolism; D006900:Hydroxylation; D066298:In Vitro Techniques; D007783:Lactones / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002396:Catechols; D007783:Lactones; D020723:Glucuronic Acid; D002394:Catechol O-Methyltransferase; C005197:alternariol; C018206:alternariol monomethyl ether