Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

Abstract

Sommansson A, Saudi WSW, Nylander O, Sjöblom M. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo. Am J Physiol Gastrointest Liver Physiol 305: G95-G105, 2013. First published May 2, 2013; doi:10.1152/ajpgi.00074.2013.-Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ϳ30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of 51 Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25-100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol-and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HClinduced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol-and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes

“…The serotonin receptor (HTR1B) is also involved in the control of vascular permeability in the brain (Riad et al, 1998), while substance P (TAC1) regulates vascular permeability in the intestine, skin and brain (Annunziata et al, 2002;Holzer, 1998;Lordal et al, 1996) . Somatostatin is also involved in the control of vascular permeability via SSTR5 and tight junction control (Lei et al, improves duodenal barrier function in ethanol treated rats (Sommansson et al, 2013). Adrenaline increases intestinal permeability in rats via the beta-2 receptor (ADRB2) (Lange and Delbro, 1995) and dopamine inhibits vasopressin (AVP)-dependent sodium transport and water permeability in rat kidney cortical collecting ducts via the DRD4 receptor (Sun and Schafer, 1996).While glutamate and GABA (gaba transaminase and glutamate decarboxylase: ABAT GAD1 ) are primarily brain neurotransmitters, GABA is able to accelerate skin barrier repair in an in vitro model using cultured keratinocytes while glutamate has the opposite effect.…”

The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions

“…Gut permeability arises as a consequence of a loosening of the tight junctions that closely link the cells lining the gut. A number of factors have been shown to increase gut permeability, including dietary fats [7], stress [6] and alcohol [8], including binge alcohol drinking [9], whilst a number of factors can decrease permeability or help to maintain gut tight junction integration, including dietary whole grains [10] and melatonin [4], with the latter preventing the effects of alcohol on gut permeability [8]. Recent work on the role of gut permeability in other medical conditions has focussed on its impact in the aetiology and course of depression, in turn driving the association of recurrent depression with other medical conditions, including Alzheimer's disease [11].…”

“…Dietary factors [3], alcohol [4], variations in gut microbials [5] and stress [6] can all regulate gut permeability, thereby having an impact via the immune system on a wide range of medical disorders. Here, we focus on the role of melatonin in the gut, highlighting its role in gut permeability and treatment.…”

Melatonin heals the gut

“…Hence, this being one of the contributing factors to the positive effects of melatonin on gastrointestinal disorders. The same group has also shown that intravenous application of melatonin prevents alcoholinduced augmentation of the paracellular permability and motoractivity in rats (Sommansson et al 2013b). In the work now presented in Acta Physiologica, the authors continue their studies to investigate if also oral application of melatonin would have the same effect (Sommansson et al 2014).…”

“…Dysfunction of the small intestinal barrier function with increased permeability is a common clinical observation in patients with inflammatory bowel syndrome (IBS) and alcoholic liver disease (Sommansson et al 2013b). Therapeutic administration of the night hormone melatonin has shown to be beneficial, and clinical studies have demonstrated attenuated abdominal pain in IBS (Song et al 2005).…”