Acetaminophen changes intestinal epithelial cell membrane properties, subsequently affecting absorption processes

Otmar Höglinger, Christine Schäfer, klaus schröder, Mohammad Schäfer

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

11 Zitate (Scopus)

Abstract

Background/Aims: Acetaminophen (APAP) effects on intestinal barrier properties are less investigated. APAP may lead to a changed bioavailability of a subsequently administered drug or diet in the body. We investigated the influence of APAP on enterocytic cell membrane properties that are able to modify the net intestinal absorption of administered substances across the Caco-2 barrier model. Methods: The effect of APAP on cytotoxicity was measured by LDH assay, TER value and cell capacitance label-free using impedance monitoring, membrane permeability by FITC-dextrans, and efflux transporter MDR1 activity by Rh123. APAP levels were determined by HPLC analysis. Cell membrane topography and microvilli were investigated using SEM and intestinal alkaline phosphatase (Alpi) and tight junction protein 1 (TJP1) expression by western blot analysis. Results: APAP changed the apical cell surface, reduced the number of microvilli and protein expression of Alpi as a brush border marker and TJP1, increased the membrane integrity and concurrently decreased cell capacitance over time. In addition, APAP decreased the permeability to small molecules and increased the efflux transporter activity, MDR1. Conclusion: APAP alters the Caco-2 cell membrane properties by different mechanisms and reduces the permeability to administered substances. These findings may help to optimize therapeutic implications.

OriginalspracheEnglisch
Seiten (von - bis)431-447
Seitenumfang17
FachzeitschriftCellular Physiology and Biochemistry
Jahrgang32
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - Sep 2013

Schlagwörter

  • Acetaminophen
  • intestinal barrier model
  • membrane properties
  • impedance

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