Sodium caprate-induced increases in intestinal permeability and epithelial damage are prevented by misoprostol

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Title: Sodium caprate-induced increases in intestinal permeability and epithelial damage are prevented by misoprostol
Authors: Brayden, David James
Maher, Sam
Bahar, Bojlul
Walsh, Edwin G.
Permanent link: http://hdl.handle.net/10197/6622
Date: Aug-2015
Abstract: Epithelial damage caused by intestinal permeation enhancers is a source of debate over their safety. The medium chain fatty acid, sodium caprate (C10), causes reversible membrane perturbation at high dose levels required for efficacy in vivo, so the aim was to model it in vitro. Exposure of Caco-2 monolayers to 8.5mM C10 for 60min followed by incubation in fresh buffer led to (i) recovery in epithelial permeability (i.e. transepithelial electrical resistance (TEER) and apparent permeability coefficient (Papp) of [(14)C]-mannitol), (ii) recovery of cell viability parameters (monolayer morphology, plasma membrane potential, mitochondrial membrane potential, and intracellular calcium) and (iii) reduction in mRNA expression associated with inflammation (IL-8). Pre-incubation of monolayers with a mucosal prostaglandin cytoprotectant was attempted in order to further decipher the mechanism of C10. Misoprostol (100nM), inhibited C10-induced changes in monolayer parameters, an effect that was partially attenuated by the EP1 receptor antagonist, SC51322. In rat isolated intestinal tissue mucosae and in situ loop instillations, C10-induced respective increases in the [(14)C]-mannitol Papp and the AUC of FITC-dextran 4000 (FD-4) were similarly inhibited by misoprostol, with accompanying morphological damage spared. These data support a temporary membrane perturbation effect of C10, which is linked to its capacity to mainly increase paracellular flux, but which can be prevented by pre-exposure to misoprostol.
Funding Details: Irish Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Copyright (published version): 2015 Elsevier
Keywords: Oral peptide delivery;Medium chain fatty acids;Sodium caprate;Caco-2 monolayers;Intestinal permeation enhancers;Cytotoxicity assays
DOI: 10.1016/j.ejpb.2015.05.013
Language: en
Status of Item: Peer reviewed
Appears in Collections:Irish Drug Delivery Network Research Collection
Veterinary Medicine Research Collection

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