Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

David Dahlgren, Maria-José Cano-Cebrián, Per M Hellström, Alkwin Wanders, Markus Sjöblom, Hans Lennernäs

Research output: Contribution to journalJournal articleResearchpeer-review

6 Citations (Scopus)
14 Downloads (Pure)

Abstract

A healthy intestinal barrier prevents uptake of allergens and toxins, whereas intestinal permeability increases following chemotherapy and in many gastrointestinal and systemic diseases and disorders. Currently, there are no approved drugs that target and repair the intestinal epithelial barrier while there is a medical need for such treatment in gastrointestinal and related conditions. The objective of this single-pass intestinal perfusion study in rats was to investigate the preventive cytoprotective effect of three mucosal protective drugs-melatonin, misoprostol, and teduglutide-with different mechanisms of action on an acute jejunal injury induced by exposing the intestine for 15 min to the anionic surfactant, sodium dodecyl sulfate (SDS). The effect was evaluated by monitoring intestinal clearance of 51Cr-labeled ethylenediaminetetraacetate and intestinal histology before, during, and after luminal exposure to SDS. Our results showed that separate pharmacological pretreatments with luminal misoprostol and melatonin reduced acute SDS-induced intestinal injury by 47% and 58%, respectively, while their use in combination abolished this injury. This data supports further development of drug combinations for oral treatments of conditions and disorders related to a dysregulated or compromised mucosal epithelial barrier.

Original languageEnglish
Article number6771
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
Pages (from-to)1-13
Number of pages13
ISSN1661-6596
DOIs
Publication statusPublished - 15 Sept 2020

Keywords

  • Gastrointestinal physiology
  • Intestinal barrier dysfunction
  • Intestinal permeability
  • Single-pass intestinal perfusion

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