Sertraline and Citalopram Actions on Gut Barrier Function
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ORIGINAL ARTICLE
Sertraline and Citalopram Actions on Gut Barrier Function Johana Eyzaguirre‑Velásquez1 · María Paz González‑Toro1 · Camila González‑Arancibia1 · Jorge Escobar‑Luna1 · Caroll J. Beltrán2 · Javier A. Bravo1 · Marcela Julio‑Pieper1 Received: 25 September 2020 / Accepted: 29 October 2020 © The Author(s) 2020
Abstract Introduction Disruption of intestinal barrier is a key component to various diseases. Whether barrier dysfunction is the cause or effect in these situations is still unknown, although it is believed that translocation of luminal content may initiate gastrointestinal or systemic inflammatory disorders. Since trauma- or infection-driven epithelial permeability depends on Toll-like receptor (TLR) activity, inhibition of TLR signaling has been proposed as a strategy to protect intestinal barrier integrity after infection or other pathological conditions. Recently, selective serotonin recapture inhibitors including sertraline and citalopram were shown to inhibit TLR-3 activity, but the direct effects of these antidepressant drugs on the gut mucosa barrier remain largely unexplored. Materials and methods To investigate this, two approaches were used: first, ex vivo studies were performed to evaluate sertraline and citalopram-driven changes in permeability in isolated intestinal tissue. Second, both compounds were tested for their preventive effects in a rat model of disrupted gut barrier, induced by a low protein (LP) diet. Results Only sertraline was able to increase transepithelial electrical resistance in the rat colon both when used in an ex vivo (0.8 μg/mL, 180 min) or in vivo (30 mg/kg p.o., 20 days) fashion. However, citalopram (20 mg/kg p.o., 20 days), but not sertraline, prevented the increase in phospho–IRF3 protein, a marker of TLR-3 activation, in LP-rat ileum. Neither antidepressant affected locomotion, anxiety-like behaviours or stress-induced defecation. Conclusion Our data provides evidence to support the investigation of sertraline as therapeutic strategy to protect intestinal barrier function under life-threatening situations or chronic conditions associated with gut epithelial disruption. Keywords Gut · Permeability · Barrier · TLR · Sertraline · Citalopram · SSRI
Introduction Maintenance of intestinal barrier integrity is essential to a healthy status. Diverse chronic disorders, including inflammatory bowel disease, diabetes, and rheumatologic disorders, are associated with a disruption of intestinal barrier function [1–3]. Moreover, a proportion of patients admitted in intensive care units due to critical illness or injury also display increased gut permeability [4, 5] which may elevate
* Marcela Julio‑Pieper [email protected] 1
Grupo de NeuroGastroBioquímica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
Laboratorio de Inmunogastroenterología, Servicio de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile
2
the risk of sepsis, multiple organ failure, and probably th
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