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

Files in This Item:
 File SizeFormat
DownloadBrayden_Researchgate_21052015.docx534.74 kBMicrosoft Word
Title: Sodium caprate-induced increases in intestinal permeability and epithelial damage are prevented by misoprostol
Authors: Brayden, David JamesMaher, SamBahar, BojlulWalsh, Edwin G.
Permanent link: http://hdl.handle.net/10197/6622
Date: Aug-2015
Online since: 2016-05-27T01:00:13Z
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
Journal: European Journal of Pharmaceutics and Biopharmaceutics
Volume: 94
Start page: 194
End page: 206
Copyright (published version): 2015 Elsevier
Keywords: Oral peptide deliveryMedium chain fatty acidsSodium caprateCaco-2 monolayersIntestinal permeation enhancersCytotoxicity assays
DOI: 10.1016/j.ejpb.2015.05.013
Language: en
Status of Item: Peer reviewed
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:Irish Drug Delivery Network Research Collection
Veterinary Medicine Research Collection

Show full item record

SCOPUSTM   
Citations 20

21
Last Week
0
Last month
0
checked on Sep 12, 2020

Page view(s) 5

2,741
Last Week
3
Last month
17
checked on May 21, 2022

Download(s) 50

507
checked on May 21, 2022

Google ScholarTM

Check

Altmetric


If you are a publisher or author and have copyright concerns for any item, please email research.repository@ucd.ie and the item will be withdrawn immediately. The author or person responsible for depositing the article will be contacted within one business day.