Oxidative metabolism of the mycotoxins alternariol and alternariol-9-methyl ether in precision-cut rat liver slices in vitro

Scope: 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. Methods and 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. Conclusion: 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.