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
| Autor: | Hernán Speisky, Elias Atala, Adriano Costa de Camargo, Hermann Zbinden-Foncea, Oscar Brunser, José Herranz, Jocelyn Fuentes |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Antioxidant NF-E2-Related Factor 2 Endocrinology Diabetes and Metabolism Metabolite medicine.medical_treatment Indomethacin Clinical Biochemistry Pharmacology medicine.disease_cause Biochemistry Permeability Rats Sprague-Dawley chemistry.chemical_compound In vivo Onions medicine Animals Humans Intestinal Mucosa Molecular Biology Benzofurans Peroxidase Nutrition and Dietetics Plant Extracts Chemistry Anti-Inflammatory Agents Non-Steroidal Interleukin-8 NF-kappa B In vitro Rats Dextran Gastric Mucosa Paracellular transport Quercetin Caco-2 Cells Oxidation-Reduction Oxidative stress |
| Zdroj: | The Journal of Nutritional Biochemistry. 100:108886 |
| ISSN: | 0955-2863 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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