The protease inhibitor darunavir prevents esophagitis and impairments in esophageal barrier function in a mouse model of GERD.
Abstract
Gastric reflux induces esophageal mucosal inflammation, partially mediated by the activation of hypoxia inducible factor 2α (HIF-2α). Pepsin, present in the refluxate, amplifies this inflammatory process and exacerbates tissue injury. Therefore, pepsin inhibition represents a promising strategy to reduce inflammation and preserve esophageal mucosal integrity. In this study, we evaluated the effects of darunavir, a protease inhibitor presently used to treat human immunodeficiency virus infection, in a gastroesophageal reflux disease (GERD) model in Swiss mice. Animals were anesthetized (ketamine and xylazine) and subjected to partial pyloric ligation and total ligation of the gastric fundus. Four experimental groups were established: sham (control), sham + darunavir, GERD, and GERD + darunavir. After 3 days, animals were euthanized, and the esophagus was collected to measure wet weight (edema), myeloperoxidase (MPO) activity, and keratinocyte-derived cytokines (KC). Western blot was performed for HIF-2α and tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCLD). Histology with analysis of dilation of the intercellular space (DIS). Esophageal barrier function was assessed by transepithelial electrical resistance and fluorescein as an index of paracellular permeability. Darunavir's antipeptic activity was also demonstrated in vitro. GERD-induced inflammation, with significant increases in edema, MPO, KC, DIS, histological changes and HIF-2α, and disrupted barrier…
Read the paper
Related studies
- Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use
- Ivth brazilian consensus conference on helicobacter pylori infection
- A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia
- S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013
- Step-by-step management of refractory gastresophageal reflux disease
- Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.