title: Acetaminophen changes intestinal epithelial cell membrane properties, subsequently affecting absorption processes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: BioMed-zet Life Science GmbH, Linz, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Schäfer
authors.forename: Klaus Rudolf
authors.initials: KR
authors.lastname: Schröder
authors.forename: Otmar
authors.initials: O
authors.lastname: Höglinger
authors.forename: Sajjad
authors.initials: S
authors.lastname: Tollabimazraehno
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Lornejad-Schäfer
mesh_terms: D000042:Absorption / Q000187:drug effects; D000082:Acetaminophen / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D058851:GPI-Linked Proteins; D000082:Acetaminophen; C063088:ALPI protein, human; D000469:Alkaline Phosphatase