Protection against indomethacin-induced loss of intestinal epithelial barrier function by a quercetin oxidation metabolite present in onion peel: In vitro and in vivo studies

Jocelyn Fuentes, Oscar Brunser, Elías Atala, José Herranz, Adriano Costa de Camargo, Hermann Zbinden-Foncea, Hernán Speisky

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Oxidative stress is directly implicated in the loss of intestinal epithelial barrier function (IEBF) induced by non-steroidal anti-inflammatory drugs (NSAIDs). Previous studies by our research team demonstrated that 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite that naturally occurs in onion peels, exhibits an antioxidant potency notably higher than quercetin. Thus, we assessed the potential of BZF and a BZF-rich onion peel aqueous extract (OAE) to protect against the loss of IEBF in Caco-2 cell monolayers and in rats exposed to indomethacin. In vitro, pure BZF and OAE standardized in BZF (100 nM), protected against the drop in transepithelial electrical resistance by 70 – 73%. Likewise, it prevented the increase in fluorescein-isothiocyanate labelled dextran (FITC-dextran) paracellular transport by 74% and oxidative stress by 84 – 86%. In vivo, BZF, given orally at a dose 80 µg/Kg bw as OAE, totally abolished a 30-fold increase in FITC-dextran serum concentration induced by indomethacin. This effect was dose-dependent and largely conserved (85%) when OAE was given 180-min prior to indomethacin. The IEBF-protective effect of OAE was accompanied by a full prevention of the NF-ĸB activation, and the increases in interleukine-8 secretion and myeloperoxidase activity induced by indomethacin. The protection was also associated with a 21-fold increase in Nrf2, and a 7-fold and 9-fold increase in heme oxygenase-1 and NAD(P)H-quinone oxidoreductase 1, respectively. The IEBF-protecting effect of OAE involves, most likely, its dual capacity to activate Nrf2 while inhibiting NF-ĸB activation. The extremely low doses of BZF needed to promote such actions warrants extending its IEBF-protective effects to other NSAIDs.

Original languageEnglish
Article number108886
JournalJournal of Nutritional Biochemistry
Volume100
DOIs
StatePublished - 1 Feb 2022

Keywords

  • antioxidants
  • benzofuranone
  • IL-8
  • Indomethacin
  • intestinal epithelial barrier function
  • MPO
  • NF-kB
  • Nrf2
  • onion peel extract
  • oxidative stress
  • quercetin
  • TEER

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