Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia–Reperfusion Injury in a Rat

Abstract

Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.

N-Acetyl Serotonin Alleviates Oxidative Damage by Activating Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Porcine Enterocytes

“…Moreover, NAS has been approved by the FDA for treatment of neurological disorders and stroke [29]. Recent studies have shown that NAS protects against oxidative damage in neurons, erythrocytes, retinal cells, lung epithelial cells, lymphocytes, and enterocytes [17,[29][30][31][32]. However, the underlying mechanisms responsible for the beneficial effect of NAS are largely unknown.…”

“…Moreover, in vitro studies have shown that NAS has a more potent antioxidant capacity than melatonin [15]. NAS administration protects ischemia-reperfusion-induced mucosal damage in the jejunum and ileum of rats [17]. About 25% of dietary Trp is degraded by the porcine small intestine during its first pass into the portal vein and leads to the generation of multiple metabolites including serotonin, melatonin, and NAS [18].…”

The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates

“…While 5-HT predominantly exerts proinflammatory effects, emerging evidence points to the anti-inflammatory and anti-oxidant effects of its endogenous fatty acid-conjugates, Nacyl 5-HTs, present in the gut [38][39][40][41]138]. Our laboratory uncovered that docosahexaenoylserotonin (DHA-5-HT), the conjugate of 5-HT with the n-3 poly unsaturated long chain fatty acid (LC PUFA) DHA, has anti-inflammatory effects both in mouse macrophages as well as in human peripheral blood mononuclear cells (PBMCs), by attenuating release of key inflammatory mediators [40,41].…”

“…Furthermore, N-acyl-5-HTs with varying fatty acid moieties were reported to exert anti-inflammatory, anti-oxidant, and neuroprotective effects in a number of in vivo animal disease models [38,39,[142][143][144][145]. In an inflammatory in vivo gut model, the SCFA conjugate of 5-HT, N-acetyl-5-HT (also called NAS), has been shown to prevent gut mucosal damage and inhibit programmed cell death following intestinal ischemia-reperfusion (IR) in rats [38]. Intestinal IR is a multifactorial pathophysiological process involving nonspecific damage of the gut, which can occur during trauma, sepsis, or shock.…”

“…These include the well-known group of the Nacyl-ethanolamides [31][32][33][34][35][36] and 2-acyl glycerols [37], of which several are classified as endocannabinoids. More recently, fatty acid conjugates with serotonin (5-HT) emerged as a class of molecules with immune-modulatory and anti-oxidant effects [38,39]. Of these, the 5-HT acyl-conjugates with long chain fatty acids (LCFAs) are present in the GI tract and the available evidence points towards a role in modulating immune responses and relevance for inflammatory pathologies of gut [40,41].…”