1. GYY4137 ameliorates intestinal barrier injury in a mouse model of endotoxemia.
- Author
-
Chen S, Bu D, Ma Y, Zhu J, Sun L, Zuo S, Ma J, Li T, Chen Z, Zheng Y, Wang X, Pan Y, Wang P, and Liu Y
- Subjects
- Animals, Caco-2 Cells, Cell Membrane Permeability, Electric Impedance, Endotoxemia immunology, Endotoxemia pathology, Endotoxemia physiopathology, Enterocytes drug effects, Enterocytes immunology, Enterocytes metabolism, Enterocytes ultrastructure, Gastrointestinal Agents pharmacology, Gene Expression Regulation drug effects, Humans, Interferon-gamma antagonists & inhibitors, Interferon-gamma metabolism, Intestinal Mucosa immunology, Intestinal Mucosa physiopathology, Intestinal Mucosa ultrastructure, Lipopolysaccharides antagonists & inhibitors, Lipopolysaccharides toxicity, Male, Mice, Inbred C57BL, Morpholines pharmacology, Organothiophosphorus Compounds pharmacology, Protective Agents pharmacology, Protective Agents therapeutic use, Random Allocation, Tight Junction Proteins genetics, Tight Junction Proteins metabolism, Tight Junctions drug effects, Tight Junctions immunology, Tight Junctions metabolism, Tight Junctions ultrastructure, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha metabolism, Apoptosis drug effects, Disease Models, Animal, Endotoxemia drug therapy, Gastrointestinal Agents therapeutic use, Intestinal Mucosa drug effects, Morpholines therapeutic use, Organothiophosphorus Compounds therapeutic use
- Abstract
Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H
2 S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF-α/IFN-γ and a mouse model of endotoxemia were used in this study. The results suggested that GYY4137 significantly attenuated LPS or TNF-α/IFN-γ induced increased Caco-2 monolayer permeability. The decreased expression of TJ (tight junction) proteins induced by LPS and the altered localization of TJs induced by TNF-α/IFN-γ was significantly inhibited by GYY4137; similar results were obtained in vivo. Besides, GYY4137 promoted the clinical score and histological score of mice with endotoxemia. Increased level of TNF-α/IFN-γ in the plasma and increased apoptosis in colon epithelial cells was also attenuated by GYY4137 in mice with endotoxemia. This study indicates that GYY4137 preserves the intestinal barrier function in the context of endotoxemia via multipathways and throws light on the development of potential therapeutic approaches for endotoxemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2016
- Full Text
- View/download PDF