Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Melatonin

  • endogenous melatonin
  • exogenous melatonin
  • hormone melatonin
  • plasma melatonin

  • Terms modified by Melatonin

  • melatonin administration
  • melatonin alone
  • melatonin biosynthesis
  • melatonin concentration
  • melatonin level
  • melatonin pretreatment
  • melatonin production
  • melatonin receptor
  • melatonin release
  • melatonin rhythm
  • melatonin secretion
  • melatonin synthesis
  • melatonin therapy
  • melatonin treatment

  • Selected Abstracts


    Ahmed M Mohamadin
    SUMMARY 1Melatonin (MT) is a pineal hormone that is also abundant in the gut and has a well known role in scavenging oxygen free radicals. The aim of the present study was to evaluate the potential protective effects of MT against H2O2 -induced gastric lesions in rats. 2An experimental model of gastric ulceration was established in rats using 15% H2O2. Melatonin (12.5, 25 or 50 mg/kg, intagastrically) was administered to rats 30 min before H2O2 challenge. 3Intragastric administration of H2O2 resulted in haemorrhagic lesions in the fundic area of the stomach. Furthermore, H2O2 induced gastric oxidative stress, as indicated by depletion of reduced glutathione (GSH), inhibition of glutathione peroxidase (GPx) activity and elevation of malonedialdehyde (MDA) levels. These effects were accompanied by decreased gastric tissue levels of prostaglandin (PG) E2 and nitric oxide (NO), as well as increased levels of tumour necrosis factor (TNF)-,. Administration of MT (12.5, 25 or 50 mg/kg) 30 min before H2O2 significantly attenuated the development of gastric lesions in a dose-dependent manner. The protective effects of MT were accompanied by significant inhibition of the H2O2 -induced reduction in gastric content of GSH and GPx activity and elevation in MDA levels. Furthermore, MT antagonized H2O2 -induced reduction of gastric PGE2 and NO levels and elevation of TNF-,. 4In conclusion, MT protects rat gastric mucosa against H2O2 -induced damage. The observed protective effects of MT can be attributed, at least in part, to its anti-oxidant properties, preservation of PGE2 and NO levels, as well as inhibition of TNF-, induction in gastric tissues. [source]


    Hua-Li Li
    SUMMARY 1Several groups have reported that melatonin produces a significant decrease in blood pressure in mammals and that pinealectomy in rats causes hypertension. The purpose of the present study was to investigate the effects of melatonin and bicuculline methiodide on the blood pressure of rats, both in the developing and fully developed stage of stress-induced hypertension (SIH). 2Rats with SIH were generated by mild electric foot shocks for 15 days, after which tail arterial systolic pressure and plasma angiotensin (Ang) II levels were measured. The effects of melatonin injections (i.p. or i.c.v.) on mean arterial pressure (MAP) in rats with SIH were also determined. 3Pretreatment with 1 mg/kg, i.p., melatonin significantly diminished the elevated tail arterial systolic pressure and plasma AngII levels caused by 15 days stress. The suppressive effects of melatonin were blocked by i.p. injection of 1 mg/kg bicuculline methiodide, an antagonist of the GABAA receptor. 4Intraperitoneal (0.2, 0.5 and 1 mg/kg) or i.c.v. (0.15 and 1.5 µg/3 µL) injection of melatonin produced a dose-dependent lowering of MAP in rats with SIH. The antihypertensive response induced by melatonin was blocked by injection of both 1 mg/kg, i.p., and 1.5 × 106 µg/3 µL, i.c.v., bicuculline methiodide. 5In conclusion, melatonin not only prevents increases in blood pressure during the developing stage of SIH, but can also reduce the blood pressure of rats that have already developed SIH. The antihypertensive effect of melatonin may be mediated by GABAA receptors through inhibition of plasma AngII levels. [source]


    Chun-Mei Xia
    SUMMARY 1Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. 2The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. 3Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. 4The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. 5The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM. [source]

    Melatonin therapy for headache disorders

    Mario F.P. Peres
    Abstract Even though efficacy is often the most important consideration for patient preference in migraine prevention, currently available medications do not meet patient expectation. Efficacy is in the range of 50% reduction in migraine attacks in 50% of patients studied for the best medications. Therefore, new options for migraine treatment are needed. Melatonin has been considered a good candidate for migraine and other headaches prevention due to its favorable mechanisms of action and excellent tolerability profile. In this article, we review the putative role of the pineal gland and melatonin in migraine pathophysiology and treatment. Drug Dev Res 68:329,334, 2007. © 2007 Wiley-Liss, Inc. [source]

    Sensitive Adsorptive Stripping Voltammetric Methodologies for the Determination of Melatonin in Biological Fluids

    ELECTROANALYSIS, Issue 9 2003
    L. Corujo-Antuńa
    Abstract The reversible redox process that melatonin presented on carbon paste electrodes was the basis of a sensitive methodology for the determination of this hormone. From all the processes presented by this hormone, this was never used before as the basis of voltammetric measurements for melatonin determination. Therefore, parameters that affected the cyclic voltammetric signal were studied. A limit of detection as low as 9×10,11,M was obtained when optimized alternating current voltammetry was employed. The reproducibility was excellent due to an adequate pretreatment of the solid electrode (RSD=2.7%, n=10). A comparison with methodologies that employ different electrochemical techniques from the point of view of their analytical characteristics was made. This methodology has proved to be suitable for the determination of melatonin in biological fluids. [source]

    Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy

    G. Williams
    Abstract Background Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright-light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet-lag and shift workers. Design Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF-36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these. Results Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0·8 h; P = 0·04) with phototherapy. Conclusion Melatonin and bright-light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated. [source]

    Melatonin inhibits hippocampal long-term potentiation

    Louisa M. Wang
    Abstract The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nm producing an ,,50% inhibition of long-term potentiation magnitude. Long-duration melatonin treatments of 6 h were also effective at reducing the magnitude of long-term potentiation. Melatonin (100 nm) did not alter baseline evoked responses or paired-pulse facilitation recorded at this synapse. The inhibitory actions of melatonin were prevented by application of the melatonin (MT) receptor antagonist luzindole as well as the MT2 receptor subtype antagonist 4-phenyl-2-propionamidotetraline. These inhibitory actions of melatonin were lost in mice deficient in MT2 receptors but not those deficient in MT1 receptors. In addition, application of the protein kinase A inhibitor H-89 both mimicked the effects of melatonin and precluded further inhibition by melatonin. Finally, the application an activator of adenylyl cyclase, forskolin, overcame the inhibitory effects of melatonin on LTP without affecting the induction of long-term potentiation on its own. These results suggest that hippocampal synaptic plasticity may be constrained by melatonin through a mechanism involving MT2-receptor-mediated regulation of the adenylyl cyclase,protein kinase A pathway. [source]

    Diurnal rhythms in neurohypophysial function

    Mary L. Forsling
    The neurohypophysial hormones oxytocin and vasopressin show daily rhythms of secretion with elevated hormone release during the hours of sleep. This pattern can be modulated by ovarian steroids and alters with age. The pattern appears to be due in part to the nocturnal increase in melatonin secretion, which stimulates hormone release in man, while being inhibitory in the rat. Pinealectomy alters both the 24 h pattern of neurohypophysial hormone release in the rat and the firing rate of magnocellular supraoptic nucleus neurones. There is also a reduced hormone release in response to hypovolaemia and raised plasma sodium concentration compared to sham operated animals, with a smaller increase in neuronal activity, as determined by immediate-early gene expression. The normal responses can be restored by nocturnal administration of melatonin. Melatonin also influences the neurohypophysial hormone response in the human to known stimuli of release, such as raised plasma osmolality, exercise and insulin-induced hypoglycaemia. Recent studies have revealed that not only does the release of vasopressin and oxytocin vary over each 24 h, but the respective renal and pregnant uterine responses also show diurnal variations. [source]

    Effect of Exogenous Melatonin on Mood and Sleep Efficiency in Emergency Medicine Residents Working Night Shifts

    Milan Jockovich MD
    Abstract. Objective: To determine whether melatonin taken prior to attempted daytime sleep sessions will improve daytime sleep quality, nighttime sleepiness, and mood state in emergency medicine (EM) residents, changing from daytime to nighttime work schedules. Methods: A prospective, randomized, double-blind crossover design was used in an urban emergency department. Emergency medicine residents who worked two strings of nights, of at least three nights' duration each, and separated by at least one week of days were eligible. Subjects were randomized to receive either melatonin 1 mg or placebo, 30 to 60 minutes prior to their daytime sleep session, for three consecutive days after each night shift. Crossover to the other agent occurred during their subsequent night shifts. Objective measures of quality of daytime sleep were obtained using the Actigraph 1000. This device measures sleep motion and correlates with sleep efficiency, total sleep time, time in bed, and sleep latency. The Profile of Mood States (POMS) and the Stanford Sleepiness Scale (SSS) were also used to quantify nighttime mood and sleepiness. Results: Among the 19 volunteers studied, there was no difference in sleep efficiency (91.16% vs 90.98%, NS), sleep duration (379.6 min vs 342.7 min, NS), or sleep latency (7.59 min vs 6.80 min, NS), between melatonin and placebo, respectively. In addition, neither the POMS total mood disturbance (5.769 baseline vs 12.212 melatonin vs 5.585 placebo, NS) nor the SSS (1.8846 baseline vs 2.2571 melatonin vs 2.1282 placebo, NS) demonstrated a statistical difference in nighttime mood and sleepiness between melatonin and placebo. Conclusions: There are no beneficial effects of a 1-mg melatonin dose on sleep quality, alertness, or mood state during night shift work among EM residents. [source]

    Effects of melatonin and caffeic acid phenethyl ester on testicular injury induced by myocardial ischemia/reperfusion in rats

    Mukaddes E
    Abstract Experimental studies indicate that ischemia/reperfusion (I/R) causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative injury on testicular damage following myocardial I/R injury and the effects of antioxidant agents, melatonin and caffeic acid phenethyl ester (CAPE), on testicular injury were investigated. As far as we know, this is the first report demonstrating that myocardial I/R induces damage to the testes. Thirty-two male Wistar rats were randomly divided into four groups: sham operation (SO), I/R + vehicle, I/R + melatonin, and I/R + caffeic acid phenethyl ester. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Serum nitric oxide (NO) and malondialdehyde (MDA) levels and morphological changes were examined. I/R was accompanied by a significant increase in serum MDA and NO levels, whereas, melatonin and CAPE administration significantly reduced these values. Melatonin was more efficient in reducing MDA levels than CAPE (P < 0.05). I/R induced myocardial damage, manifested as the histopathological evidence of intracellular vacuolization, interstitial edema, neutrophil infiltration and coagulative necrosis. I/R + vehicle group showed many histological alterations such as focal tubular atrophy, and degeneration and disorganization of the seminiferous epithelium in testes. The number of atrophic tubules and degenerating cells was significantly higher in I/R + vehicle group than that of SO group. Melatonin and CAPE significantly reduced the number of degenerating cells; additionally, melatonin reduced the number of atrophic tubules (P < 0.05). Our results indicate that myocardial I/R induces severe testicular damage and antioxidant agents, especially melatonin, have protective effects on testicular injury after myocardial I/R. Our data emphasize that oxygen-based reactants may play a central role in remote organ injury. [source]

    Cluster headache: the challenge of clinical trials.

    HEADACHE, Issue 3 2003
    K Moore
    Curr Pain Headache. Rep 2002 Feb;6(1):52-56 The design and execution of clinical trials poses special problems for cluster headache. Although there is less inter-individual and intra-individual variability of attacks than seen with migraine, the brevity of attacks, spontaneous remissions unrelated to treatment, and the relative rarity of cluster headaches challenge investigators. The International Headache Society has developed guidelines that represent a compromise between scientific rigor and practicality. Only injectable sumatriptan for acute attacks and verapamil for prophylaxis have demonstrated a robust therapeutic effect in controlled clinical trials. Comment: Kenneth Moore raises important methodological considerations. It is possible to undertake crossover trials comparing different active treatments? He is correct in his assertion that few agents show robust efficacy. A major issue relates to the proportion of patients with episodic versus chronic cluster headache where efficacy of active treatments can vary. For example, oral zolmitriptan was effective against placebo only in those patients with episodic disease (Bahra A, Gawel MJ, Hardebo JE, Millson DS, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832-1839). And a set of small studies on melatonin and cluster demonstrate the problems Dr. Moore describes. In one study (Leone M, D'Amico D, Moschiano F, Fraschini F, Busonne G. Metalonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16:494-496), the melatonin worked only in episodic, not chronic cluster patients. In the second study (Prinsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. Melatonin as adjuctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;42:787-792), melatonin did not work better than placebo in either episodic or chronic cluster patients. Furthermore, the paper abstracted above by Torelli and Manzoni suggests that episodic cluster may progress to chronic cluster as a result of extrinsic factors such as smoking. Finally, there are ethical issues in placebo-controlled cluster studies, given the severity of the pain and the availability of effective acute and chronic treatments. As noted above, Dr. Peter Goadsby points out the need to persevere with these studies to find nonvasoactive treatments for patients with cluster headache. DSM and SJT [source]

    Melatonin as a potential therapeutic agent in psychiatric illness

    Maria D. Maldonado
    Abstract The aim of this review was to summarize the potential use of melatonin in the treatment of mental disorders, specifically bipolar disorders, depression, and schizophrenia. To date, melatonin has been most commonly used in psychiatry because of its hypnotic, rhythm resynchronizing, and antioxidant actions. Here, we examine other properties of the melatonin including its anti-inflammatory, antinociceptive, anxiolytic, and drug detoxification actions as well as its protective effects against neural loss. The brain is an intricate sensory and motor organ which receives information from both the external and internal environments. It transduces information into complex chemical and electrical signals which are transmitted throughout the central nervous system (CNS) and the organism. The pathogenesis of mental disorders remains ambiguous and neuroinflammation has been proposed as a causative agent. We consider the potential contributions of melatonin as therapeutic agent in CNS and during neuroinflammation in mental disorders. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Melatonin and ulcerative colitis: Evidence, biological mechanisms, and future research

    Paul D. Terry PhD
    Abstract Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1 million people in the US. Current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is considerable interest in finding alternative and more tolerable treatments for this disease. Physiologic data suggest that melatonin is an important regulator of both inflammation and motility in the gastrointestinal tract, and data from in vitro studies, animal experiments, and limited studies in humans suggest that supplemental melatonin may have an ameliorative effect on colitis. In this review we summarize the evidence regarding melatonin as a possible therapeutic agent in UC and discuss possible biological mechanisms and directions for future research. (Inflamm Bowel Dis 2008) [source]

    No effect of melatonin on oxidative stress after laparoscopic cholecystectomy: a randomized placebo-controlled trial

    Background: Melatonin, an endogenous circadian regulator, also has antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the antioxidative effect of melatonin in patients undergoing laparoscopic cholecystectomy. Methods: Patients were randomized to receive 10 mg melatonin or placebo during surgery. Blood samples for analysis of malondialdehyde (MDA), ascorbic acid (AA), total ascorbic acid (TAA) dehydroascorbic acid (DHA) and C-reactive protein (CRP) were collected pre-operatively and at 5 min, 6 h and 24 h after operation. Results: Twenty patients received melatonin and 21 patients received placebo during surgery. No significant differences were observed between the groups in the oxidative stress variables MDA, TAA, AA and DHA or in the inflammatory variable CRP (repeated-measures ANOVA, P>0.05 for all variables). Conclusions: Administration of 10 mg melatonin did not reduce variables of oxidative stress in patients undergoing elective laparoscopic cholecystectomy. [source]

    Melatonin: therapeutic and clinical utilization

    A. Altun
    Summary Melatonin, acting through melatonin receptors, is involved in numerous physiological processes including circadian entrainment, blood pressure regulation, oncogenesis, retinal physiology, seasonal reproduction, ovarian physiology, immune function and most recently in inducing osteoblast differentiation. Moreover, melatonin was proved to be a potent-free radical scavenger and a broad-spectrum antioxidant. More research is required into the effects of therapeutically modulating the melatoninergic system on circadian haemodynamics and rhythm under varying physiopathological conditions and the possible impact on morbidity and mortality in humans. [source]

    The role of melatonin in immuno-enhancement: potential application in cancer

    Sandra C. Miller
    Summary Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense , not only NK cells but also T and B lymphocytes, granulocytes and monocytes , in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia, daily administration of melatonin results in a survival index of 30,40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno-enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent. [source]

    Melatonin protects against taurolithocholic-induced oxidative stress in rat liver

    Lorena Fuentes-Broto
    Abstract Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl3 and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA,+,4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA,+,4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. J. Cell. Biochem. 110: 1219,1225, 2010. Published 2010 Wiley-Liss, Inc. [source]

    Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid gland

    Malgorzata Karbownik
    Abstract Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylothiouracil (PTU),a thyrostatic drug,have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA,+,4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3,injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3 -related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3. © 2005 Wiley-Liss, Inc. [source]

    Melatonin and sleep disorders associated with intellectual disability: a clinical review

    S. G. Sajith
    Abstract Background Melatonin is used to treat sleep disorders in both children and adults with intellectual disability (ID), although it has no product license for such use. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with ID. Methods A literature search was performed using multiple electronic databases. More literature was obtained from the reference lists of papers gathered through the searches. Results Most of the studies were uncontrolled and the few controlled trials available were of small size. Melatonin appears effective in reducing sleep onset latency and is probably effective in improving total sleep time in children and adolescents with ID. It appears to be ineffective in improving night-time awakenings. Melatonin is relatively safe for short-term use. Its safety for long-term use is not established. Potential drug interactions, possible effects on puberty and concerns regarding the use of melatonin in epilepsy, asthma and depressive disorders are discussed. Conclusions Melatonin appears to be an effective sleep-initiator for children and adolescents with ID and probably has a similar effect for adults. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the ID or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin for people with ID formulated. [source]

    Local Corticosterone Infusion Enhances Nocturnal Pineal Melatonin Production In Vivo

    P. A. C. M. Fernandes
    Melatonin, an important marker of the endogenous rhythmicity in mammals, also plays a role in the body defence against pathogens and injuries. In vitro experiments have shown that either pro- or anti-inflammatory agents, acting directly in the organ, are able to change noradrenaline-induced pineal indoleamine production. Whereas corticosterone potentiates melatonin production, incubation of the gland with tumour necrosis factor-, decreases pineal hormonal production. In the present study, we show that nocturnal melatonin production measured by intra-pineal microdialysis is enhanced in pineals perfused with corticosterone at concentrations similar to those measured in inflamed animals. In vitro experiments suggest that this enhancement may be due to an increase in the activity of the two enzymes that convert serotonin to N -acetylserotonin (NAS) and NAS to melatonin. The present results support the hypothesis that the pineal gland is a sensor of inflammation mediators and that it plays a central role in the control of the inflammatory response. [source]

    Perinatal Influences of Melatonin on Testicular Development and Photoperiodic Memory in Siberian Hamsters

    C. R. Tuthill
    Abstract We assessed the influence of perinatal melatonin on reproductive development and adult responsiveness to melatonin. Testicular growth in an intermediate day length (14 : 10 h light/dark cycle) was substantially reduced in Siberian hamsters gestated by pinealectomised compared to pineal-intact females; gonadal development was normalised in offspring of pinealectomised dams that were pinealectomised at 3,4 days of age. Hamsters deprived of melatonin only during gestation, or both pre- and postnatally, underwent testicular involution during treatment with melatonin in adulthood. Photoperiodic histories acquired prenatally did not endure as long as those acquired by adult hamsters. Hamsters first exposed to melatonin in adulthood were not more proficient in acquiring photoperiodic histories than were normal males. These findings indicate that pre- versus postnatal differences in melatonin signal duration determine rates of testicular development. Exposure to melatonin perinatally does not appear to organise the neuroendocrine substrate that mediates effects of day length and melatonin on the gonads of adult hamsters. [source]

    Importance and Relevance of Melatonin to Human Biological Rhythms

    J. Arendt
    Abstract The pineal hormone melatonin is a remarkable molecule, with a conserved time-keeping function across species. It is extensively used as a self-administered remedy for sleep disturbance in countries where it is freely available, and to some extent when it is available on prescription, as in the UK. In some circumstances, notably free-running sleep disorder of the blind, it is the treatment of choice. It is also the marker rhythm of choice for the determination of circadian phase and period. This review outlines the current state of knowledge within a physiological perspective with emphasis on human biological rhythms. [source]

    Role for the Pineal and Melatonin in Glucose Homeostasis: Pinealectomy Increases Night-Time Glucose Concentrations

    S. E. La Fleur
    Abstract The effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24-h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24-h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24-h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24-h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24-h rhythm. Melatonin treatment also resulted in higher meal-induced insulin responses, probably mediated via an increased sensitivity of the ,-cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic ,-cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only. [source]

    Characterization of an Antibody to the Human Melatonin mt1 Receptor

    L. M. Williams
    Abstract Melatonin acts via high affinity, G-protein coupled, seven transmembrane domain receptors. To precisely localize these receptors, antibodies were raised in chickens against a 15 amino acid fragment at the intracellular C -terminal region of the human melatonin receptor subtype mt1 (DSSNDVADRVKWKPS, mt1338,352). A chimeric form of the receptor with a hydrophilic Flag peptide (DYKDDDDK) in sequence with the extracellular N -terminus (Flag-mt1) was generated by polymerase chain reaction and expressed in mammalian cell lines. An IgY antibody (Y31), which gave high antibody titres by enzyme-linked immunosorbent assay, was used to localize Flag-mt1 in stably transfected cells by immunofluoresence. Flag-mt1 localization with Y31 was identical to that obtained with the M5 antibody directed against the Flag epitope and was mainly localized to the Golgi apparatus with some staining at the cell surface. No staining was seen in untransfected cells with either antibody. Y31 staining was abolished using antibody preabsorbed with peptide antigen. Y31 immunofluorescence in fetal human kidney sections was restricted to nephrogenic regions and matched that of 2-(125I)iodomelatonin binding and mt1 gene expression by in situ hybridization. Y31 was used to immunoprecipitate biotinylated membrane proteins from Flag-mt1 stably transfected and untransfected CHO cells. Western blotting of immunoprecipitated proteins revealed two major bands specific to stably transfected cells, one at 63 kDa and one at 86 kDa. The first band almost certainly corresponds to the glycosylated form of Flag-mt1 and the second band to receptor dimers. Thus, Y31 antibody is suitable for use in detecting the human mt1 receptor subtype in tissues and in transfected cells. [source]

    Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence

    Germaine Escames
    Sepsis is a major cause of mortality in critically ill patients and develops as a result of the host response to infection. In recent years, important advances have been made in understanding the pathophysiology and treatment of sepsis. Mitochondria play a central role in the intracellular events associated with inflammation and septic shock. One of the current hypotheses for the molecular mechanisms of sepsis is that the enhanced nitric oxide (NO) production by mitochondrial nitric oxide synthase (mtNOS) leads to excessive peroxynitrite (ONOO,) production and protein nitration, impairing mitochondrial function. Despite the advances in understanding of its pathophysiology, therapy for septic shock remains largely symptomatic and supportive. Melatonin has well documented protective effects against the symptoms of severe sepsis/shock in both animals and in humans; its use for this condition significantly improves survival. Melatonin administration counteracts mtNOS induction and respiratory chain failure, restores cellular and mitochondrial redox status, and reduces proinflammatory cytokines. Melatonin clearly prevents multiple organ failure, circulatory failure, and mitochondrial damage in experimental sepsis, and reduces lipid peroxidation, indices of inflammation and mortality in septic human newborns. Considering these effects of melatonin and its virtual absence of toxicity, the use of melatonin (along with conventional therapy) to preserve mitochondrial bioenergetics as well as to limit inflammatory responses and oxidative damage should be seriously considered as a treatment option in both septic newborn and adult patients. This review summarizes the data that provides a rationale for using melatonin in septic shock patients. [source]

    Melatonin and circadian biology in human cardiovascular disease

    Alberto Dominguez-Rodriguez
    Abstract:, Diurnal rhythms influence cardiovascular physiology, i.e. heart rate and blood pressure, and they appear to also modulate the incidence of serious adverse cardiac events. Diurnal variations occur also at the molecular level including changes in gene expression in the heart and blood vessels. Moreover, the risk/benefit ratio of some therapeutic strategies and the concentration of circulating cardiovascular system biomarkers may also vary across the 24-hr light/dark cycle. Synchrony between external and internal diurnal rhythms and harmony among molecular rhythms within the cell are essential for normal organ biology. Diurnal variations in the responsiveness of the cardiovascular system to environmental stimuli are mediated by a complex interplay between extracellular (i.e. neurohumoral factors) and intracellular (i.e. specific genes that are differentially light/dark regulated) mechanisms. Neurohormones, which are particularly relevant to the cardiovascular system, such as melatonin, exhibit a diurnal variation and may play a role in the synchronization of molecular circadian clocks in the peripheral tissue and the suprachiasmatic nucleus. Moreover, mounting evidence reveals that the blood melatonin rhythm has a crucial role in several cardiovascular functions, including daily variations in blood pressure. Melatonin has antioxidant, anti-inflammatory, chronobiotic and, possibly, epigenetic regulatory functions. This article reviews current knowledge related to the biological role of melatonin and its circadian rhythm in cardiovascular disease. [source]

    Changes in the levels of indoleamine phytochemicals during véraison and ripening of wine grapes

    Susan J. Murch
    Abstract:, Melatonin and serotonin have previously been described in mature wine grapes and finished wines, but the metabolism of these signalling molecules in the development of wine grapes has not previously been investigated. We harvested wine grapes at different stages of development from lag phase through véraison from eight different commercial vineyards representing a diversity of growing conditions, management practices, merlot varietals and localized ecosystems to determine whether different patterns in melatonin and serotonin can be found in wine grapes during seed development and berry maturation. Melatonin was detected in 45% of the fully developed purple, postvéraison grapes but only found in 23% of prelag phase samples. However, the actual concentration of melatonin was highest in wine grapes harvested at the early stage of véraison when the seed is developing. Serotonin was not detected in any of the prelag phase grapes but was consistently detected in 30,35% of grapes harvested during the véraison transition at consistent levels of about 8,10 ,g/g. Interestingly, the nitrogen storage compound ,-aminobutyric acid was also found at about 115 ,g/g in 77% of early stage green grapes and declined in both prevalence and concentration with ripening. Together, these data are indicative of a potential role for these molecules in the development and maturation of wine grapes. [source]

    Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humans

    P. C. Konturek
    Abstract:, Melatonin and its precursor, l -tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l -tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E2, and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA-induced gastric lesions and microbleeding. Gastric mucosal generation of PGE2 was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan. [source]

    Actions of melatonin mixed with collagenized porcine bone versus porcine bone only on osteointegration of dental implants

    José Luis Calvo-Guirado
    Abstract:, This study evaluated the effect of the topical application of melatonin mixed with collagenized porcine bone on the osteointegration on the rough discrete calcium deposit (DCD) surface implants in Beagle dogs 3 months after their insertion. In preparation for subsequent insertion of dental implants, lower molars were extracted from 12 Beagle dogs. Each mandible received two parallel wall expanded platform implants with a DCD surface of 4 mm in diameter and 10 mm in length. The implants were randomly assigned to the distal sites on each mandible in the molar area and the gaps were filled with 5 mg lyophilized powdered melatonin and porcine bone and collagenized porcine bone alone. Ten histological sections per implant were obtained for histomorphometric studies. After a 4-wk treatment period, melatonin plus porcine bone significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), and new bone formation (P < 0.0001) in comparison with porcine bone alone around the implants. Melatonin plus collagenized porcine bone on DCD surface may act as a biomimetic agent in the placement of endo-osseous dental implants and enhance the osteointegration. Melatonin combined with porcine bone on DCD implants reveals more bone in implant contact at 12 wk (84.5 ± 1.5%) compared with porcine bone alone treated area (67.17 ± 1.2%). [source]

    Melatonin suppresses cyclosporine A-induced autophagy in rat pituitary GH3 cells

    Yeong-Min Yoo
    Abstract:, Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the induction of chronic nephrotoxicity including endoplasmic reticulum (ER) stress in tubular cells. Recently, it was reported that autophagy is induced by ER stress and serves to alleviate the associated deleterious effects. In the current study, CsA treatment (0,100 ,m) decreased cell survival of rat pituitary GH3 cells in a dose-dependent manner. At concentrations ranging from 1.0 to 10 ,m, CsA induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-I and LC3-II. Cells treated with 2.5 ,m CsA exhibited cytoplasmic vacuolation, indicating that CsA induces autophagy in rat pituitary GH3 cells. In the presence of 1.0,10 ,m CsA, the expression of catalase decreased while that of the ER stress markers, ER luminal binding protein (BiP) and inositol-requiring enzyme 1 alpha (IRE1,), increased as compared those levels in untreated cells. These results suggested that CsA-induced autophagy is dependent on ER stress. To determine whether melatonin would protect cells against CsA-induced autophagy, we treated rat pituitary GH3 cells with melatonin in the presence of CsA. Melatonin treatment (100 and 200 ,m) suppressed autophagy induced by 2.5 and 5 ,m CsA. Furthermore, co-treatment with 100 ,m melatonin inhibited LC3-II expression, and increased catalase and phosphorylated p-ERK levels in the presence of 2.5 and 5 ,m CsA. BiP and IRE1, expression in melatonin-co-treated cells was superior to that in cells treated with 2.5 and 5 ,m CsA alone. Thus, melatonin suppresses CsA-mediated autophagy in rat pituitary GH3 cells. [source]