Abstract
A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.
Highlights
The intestinal mucosa is a selective and dynamic barrier separating the luminal contents and the systemic circulation [1]
In the group treated with mecamylamine and sodium dodecyl sulfate (SDS), the Mean arterial blood pressure (MABP) decreased from 95 ± 3 mmHg (0–15 min) to 77 ± 7 mmHg (105–120 min) (Table 1)
Ininto the the surface-active properties of surfactants some them in to its be fluidity incorporated case of SDS, increased luminal exposure may result in lysis of the cell membrane cell membrane lipid bilayer, causing an increase in its fluidity [31]
Summary
The intestinal mucosa is a selective and dynamic barrier separating the luminal contents and the systemic circulation [1]. At high amounts in the intestinal lumen, SDS has the potential to alter epithelial barrier integrity and it has been shown to increase permeability in both the absorptive and secretive directions [23,24] It is currently unclear if the capacity of melatonin to inhibit the surfactant-induced increase in intestinal permeability is receptor mediated or antioxidative, which calls for further investigations of the mechanisms involved [24]. The receptors mediate increases in mucosal permeability induced by luminal deoxycholic acid [27], and their blocking using hexamethonium completely abolishes the protective effect of melatonin on ethanol- and wine-induced increases in intestinal permeability [19] It seems that α7 nicotinic acetylcholine receptors are involved in vagal influence on mucosal tight junctional ultrastructure [28]. Sci. 2021, 22, 10762 in jejunal epithelial permeability were evaluated by monitoring intestinal flux of 51 Crlabeled ethylenediaminetetraacetate (51 Cr-EDTA), a well-established marker for studies of mucosal barrier integrity [29]
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