Permeation and metabolism of Alternaria mycotoxins with perylene quinone structure in cultured Caco-2 cells

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• 作者：Stefanie C. Fleck (1)
  Erika Pfeiffer (1)
  Manfred Metzler (1)
  
• 关键词：Alternaria mycotoxins ; Altertoxins ; Caco ; 2 cells ; In vitro absorption ; Transwell system
• 刊名：Mycotoxin Research
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：30
• 期：1
• 页码：17-23
• 全文大小：301 KB
• 作者单位：Stefanie C. Fleck (1)
  Erika Pfeiffer (1)
  Manfred Metzler (1)
  
  1. Institute of Applied Biosciences, Unit of Food Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, 76131, Karlsruhe, Germany
  
• ISSN：1867-1632

文摘

The absorption of four Alternaria toxins with perylene quinone structures, i.e. altertoxin (ATX) I and II, alteichin (ALTCH) and stemphyltoxin (STTX) III, has been determined in the Caco-2 cell Transwell system, which represents a widely accepted in vitro model for human intestinal absorption and metabolism. The cells were incubated with the four mycotoxins on the apical side, and the concentration of the toxins in the incubation media of both chambers and in the cell lysate were determined by liquid chromatography coupled with diode array detection and mass spectrometry (LC-DAD-MS) analysis. ATX I and ALTCH were not metabolised in Caco-2 cells, but ATX II and STTX III were partly biotransformed by reductive de-epoxidation to the metabolites ATX I and ALTCH, respectively. Based on the apparent permeability coefficients (Papp), the following ranking order for the permeation into the basolateral compartment was obtained: ATX I > ALTCH >> ATX II > STTX III. Total recovery of the four toxins decreased in the same order. It is assumed that the losses of STTX III, ATX II and ALTCH in Caco-2 cells are caused by covalent binding to cell components due to the epoxide group and/or the α,β-unsaturated carbonyl group present in these toxins. We conclude from this study that ATX I and ALTCH are well absorbed from the intestinal lumen into the portal blood in vivo. For ATX II and STTX III, intestinal absorption of the parent toxins is very low, but these toxins are partly metabolised to ATX I and ALTCH, respectively, in the intestinal epithelium and absorbed as such.