مقاله انگلیسی رایگان در مورد ملاتونین: تعدیل کننده عامل ضد التهابی – هینداوی 2017

Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous indoleamine widely distributed in plants, unicellular organisms, algae, bacteria, invertebrates, and vertebrates [1–3]. In vertebrates, circulating melatonin is largely derived from the pineal gland [2, 4–6], although there are other organs such as gastrointestinal tract, epithelial hair follicles, skin, retina, salivary glands, platelets, and lymphocytes that produce melatonin [5, 7–11]. Specialized photoreceptive cells in the retina detect a restricted bandwidth of visible light; this information projects directly to the suprachiasmatic nucleus (SCN), the central circadian pacemaker, that triggers the pineal gland to produce this indoleamine during darkness [6, 12–14]. The maximal melatonin plasma concentration occurs usually 3–5 hours after darkness onset, and its level during the daily light period is low or even undetectable [15, 16]. The synthesis of melatonin is a multistep process, which starts from the essential aromatic amino tryptophan that is picked up from the blood circulation and hydroxylated, by tryptophan hydroxylase, in 5-hydroxytryptophan (5-HTP). 5-HTP is converted to serotonin by the aromatic amino acid decarboxylase, and serotonin is subsequently converted into N-acetylserotonin (NAS) by the enzyme arylalkylamine Nacetyltransferase. The final step of melatonin synthesis is the conversion of NAS to melatonin by hydroxyindole-Omethyl transferase [3, 17–19]. Pineal melatonin is immediately released into the blood stream in a circadian manner in response to the above reported photoperiodic information received via the retinopineal pathway [20–22]. Interestingly, most of the extrapineal organs, except for the retina, may not produce melatonin in a circadian manner and it is not normally released into the blood stream in any significant amount [7, 21, 23]. In these organs, melatonin presumably functions mainly as an antioxidant to protect cells from oxidative damage [7, 14, 24]. There are three major known pathways of melatonin degradation: (a) the classical hepatic catabolic pathway that generates 6-hydroxymelatonin that is then excreted via the kidney as a sulphate conjugate [3, 5, 25, 26]; (b) the alternative indolic pathway that produces 5-methoxyindole acetic acid or 5-methoxytryptophol [27, 28]; and (c) the kynuric pathway that produces N1 -acetyl-N2 -formyl-5-kynuramine (AFMK) [29–31]. In addition to the antioxidant properties of melatonin, AFMK and N1 -acetyl-5-methoxykinuramine (AMK) are two important melatonin metabolites that have excellent radical scavenging activity [5, 32, 33].