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Sample records for nocturnal melatonin elevation

  1. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials

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    Laudon M

    2011-09-01

    Full Text Available Ehud Grossman1,4, Moshe Laudon2, Nava Zisapel2,31Department of Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; 2Neurim Pharmaceuticals Ltd, Tel Aviv, Israel and 3Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; 4Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelBackground: Patients with nocturnal hypertension are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. Published studies inconsistently reported decreases in nocturnal blood pressure with melatonin.Methods: A meta-analysis of the efficacy and safety of exogenous melatonin in ameliorating nocturnal blood pressure was performed using a random effects model of all studies fitting the inclusion criteria, with subgroup analysis of fast-release versus controlled-release preparations.Results: Seven trials (three of controlled-release and four of fast-release melatonin with 221 participants were included. Meta-analysis of all seven studies did not reveal significant effects of melatonin versus placebo on nocturnal blood pressure. However, subgroup analysis revealed that controlled-release melatonin significantly reduced nocturnal blood pressure whereas fast-release melatonin had no effect. Systolic blood pressure decreased significantly with controlled-release melatonin (-6.1 mmHg; 95% confidence interval [CI] -10.7 to -1.5; P = 0.009 but not fast-release melatonin (-0.3 mmHg; 95% CI -5.9 to 5.30; P = 0.92. Diastolic blood pressure also decreased significantly with controlled-release melatonin (-3.5 mmHg; 95% CI -6.1 to -0.9; P = 0.009 but not fast-release melatonin (-0.2 mmHg; 95% CI -3.8 to 3.3; P = 0.89. No safety concerns were raised.Conclusion: Add-on controlled-release melatonin to antihypertensive therapy is effective and safe in ameliorating nocturnal hypertension, whereas fast-release melatonin is ineffective. It is necessary

  2. Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans.

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    Bonafide, Christopher P; Aucutt-Walter, Natalie; Divittore, Nicole; King, Tonya; Bixler, Edward O; Cronin, Arthur J

    2008-04-01

    Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 microg x kg x min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. Remifentanil inhibited rapid eye movement sleep (14.1 +/- 7.2% to 3.9 +/- 6.9%). The amount of slow wave sleep decreased from 6.8 +/- 7.6% to 3.2 +/- 6.1%, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.

  3. Nocturnal serum melatonin levels in sulfur mustard exposed patients with sleep disorders.

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    Mousavi, Seyyedeh Soghra; Vahedi, E; Shohrati, M; Panahi, Y; Parvin, S

    2017-12-01

    Sulfur mustard (SM) exposure causes respiratory disorders, progressive deterioration in lung function and mortality in injured victims and poor sleep quality is one of the most common problems among SM-exposed patients. Since melatonin has a critical role in regulation of sleep and awareness, this study aimed to evaluate the serum melatonin levels in SM-injured subjects. A total of 30 SM-exposed male patients and 10 controls was evaluated. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by the Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnoea was determined by the STOP-Bang questionnaire. Polysomnography (PSG) and pulmonary function tests (PFTs) were also available. Nocturnal serum melatonin levels were measured using an ELISA kit. The mean of PSQI, ESS and STOP-Bang scores in patients (11.76±3.56, 12.6±3.03 and 5.03±1.09, respectively) were significantly (pmelatonin levels in patients (29.78±19.31 pg/mL) was significantly (p=0.005) lower than that in the controls (78.53±34.41 pg/mL). Reduced nocturnal serum melatonin and respiratory disorders can be the reasons for poor sleep quality among these patients. IRCT2015092924267N1, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Fang Li; Tong Zhang

    2017-01-01

    Melatonin and gamma-aminobutyric acid (GABA) have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire (Chinese version), and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was regis-tered at ClinicalTrials.gov, identifier: NCT03202121.

  5. Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work.

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    Nagashima, Shunsuke; Osawa, Madoka; Matsuyama, Hiroto; Ohoka, Wataru; Ahn, Aemi; Wakamura, Tomoko

    2018-02-01

    The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No

  6. CIRCADIAN REGULATION METABOLIC SIGNALING MECHANISMS OF HUMAN BREAST CANCER GROWTH BY THE NOCTURNAL MELATONIN SIGNAL AND THE CONSEQUENCES OF ITS DISRUPTION BY LIGHT AT NIGHT

    Science.gov (United States)

    Blask, David E.; Hill, Steven M.; Dauchy, Robert T.; Xiang, Shulin; Yuan, Lin; Duplessis, Tamika; Mao, Lulu; Dauchy, Erin; Sauer, Leonard A.

    2011-01-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light-at-night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT1-mediated suppression of cAMP leading to blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21605163

  7. Melatonin: an Inhibitor of Breast Cancer

    Science.gov (United States)

    Hill, Steven M.; Belancio, Victoria P.; Dauchy, Robert T.; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W.; Summers, Whitney; Yuan, Lin; Frasch, Tripp; Blask, David E.

    2015-01-01

    This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 receptor, suppresses ERα mRNA expression and ERα transcriptional activity. As well, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition. Studies demonstrate that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models indicate that LEN induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer to drive breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms underpinning the epidemiologic demonstration of elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LEN. PMID:25876649

  8. Melatonin and LH secretion patterns in pubertal boys

    International Nuclear Information System (INIS)

    Fevre, M.; Boyar, R.M.; Rollag, M.D.

    1979-01-01

    Plasma melatonin and LH were measured at 20 minute intervals for 24 hours in four normal pubertal boys. All four subjects showed a significant augmentation of LH and melatonin during nocturnal sleep. There was also a significant correlation between the LH and melatonin levels (p [fr

  9. Melatonin, Light and Circadian Cycles

    Science.gov (United States)

    1989-12-25

    Neurosci Abstr 14:848. Fanget, F., Claustrat, B., Dalery, J., Brun, J., Terra , J-L, Marie-Cardine, M., and Guyotot, J. (1989) Nocturnal plasma melatonin...5- methoxytryptamine, a novel melatonin antagonist: effects on sexual matura - tion of the male and female rat and on uestrous cycles of the female rat

  10. Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

    International Nuclear Information System (INIS)

    Reiter, R.J.; Anderson, L.E.; Buschbom, R.I.; Wilson, B.W.

    1988-02-01

    Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats and the findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations. 15 refs., 1 fig., 1 tab

  11. Genetic variability of the pattern of night melatonin blood levels in relation to coat changes development in rabbits

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    Chemineau Philippe

    2004-03-01

    Full Text Available Abstract To assess the genetic variability in both the nocturnal increase pattern of melatonin concentration and photoresponsiveness in coat changes, an experiment on 422 Rex rabbits (from 23 males raised under a constant light programme from birth was performed. The animals were sampled at 12 weeks of age, according to 4 periods over a year. Blood samples were taken 7 times during the dark phase and up to 1 h after the lighting began. Maturity of the fur was assessed at pelting. Heritability estimates of blood melatonin concentration (0.42, 0.17 and 0.11 at mid-night, 13 and 15 h after lights-out respectively and strong genetic correlations between fur maturity and melatonin levels at the end of the dark phase (-0.64 indicates that (i the variability of the nocturnal pattern of melatonin levels is under genetic control and (ii the duration of the nocturnal melatonin increase is a genetic component of photoresponsiveness in coat changes.

  12. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition

    DEFF Research Database (Denmark)

    Waller, Katja Linda; Mortensen, Erik Lykke; Avlund, Kirsten

    2016-01-01

    Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were...... recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol...... and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than...

  13. Clinical Uses of Melatonin in Pediatrics

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    Emilio J. Sánchez-Barceló

    2011-01-01

    Full Text Available This study analyzes the results of clinical trials of treatments with melatonin conducted in children, mostly focused on sleep disorders of different origin. Melatonin is beneficial not only in the treatment of dyssomnias, especially delayed sleep phase syndrome, but also on sleep disorders present in children with attention-deficit hyperactivity, autism spectrum disorders, and, in general, in all sleep disturbances associated with mental, neurologic, or other medical disorders. Sedative properties of melatonin have been used in diagnostic situations requiring sedation or as a premedicant in children undergoing anesthetic procedures. Epilepsy and febrile seizures are also susceptible to treatment with melatonin, alone or associated with conventional antiepileptic drugs. Melatonin has been also used to prevent the progression in some cases of adolescent idiopathic scoliosis. In newborns, and particularly those delivered preterm, melatonin has been used to reduce oxidative stress associated with sepsis, asphyxia, respiratory distress, or surgical stress. Finally, the administration of melatonin, melatonin analogues, or melatonin precursors to the infants through the breast-feeding, or by milk formula adapted for day and night, improves their nocturnal sleep. Side effects of melatonin treatments in children have not been reported. Although the above-described results are promising, specific studies to resolve the problem of dosage, formulations, and length of treatment are necessary.

  14. Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

    Science.gov (United States)

    Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

    2015-01-01

    We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

  15. Melatonin treatment in children with therapy-resistant monosymptomatic nocturnal enuresis

    NARCIS (Netherlands)

    Merks, B. T.; Burger, H.; Willemsen, J.; van Gool, J. D.; de Jong, T. P. V. M.

    2012-01-01

    Objective: To evaluate the effects of exogenous melatonin on the frequency of wet nights, on the sleep-wake cycle, and on the melatonin profile in children with therapy-resistant MNE. Patients and methods: 24 patients were included. Patients had to maintain a diary including time of sleep and

  16. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based indu......Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a c......AMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX......) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating c...

  17. Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-kV Transmission Line.

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jack M.

    1992-06-01

    Although several kinds of biological effects of electric and magnetic fields have been reported from laboratory studies, few have been independently replicated. When this study was being planned, the suppression of nighttime melatonin in rodents was thought to represent one of the strongest known effects of these fields. The effect had been replicated by a single laboratory for 60-Hz electric fields, and by multiple laboratories for d-c magnetic fields. The primary objective of this study was to determine whether the effect of electric and magnetic fields on melatonin would also occur in sheep exposed to a high voltage transmission line. The specific hypothesis tested by this experiment was as follows: The electrical environment produced by a 60-Hz, 500-kV transmission line causes a depression in nocturnal melatonin in chronically exposed female lambs. This may mimic effects of pinealectomy or constant long-day photoperiods, thus delaying the onset of reproductive cycles. Results of the study do not provide evidence to support the hypothesis. Melatonin concentrations in the sheep exposed to the transmission line showed the normal pattern of low daytime and high nighttime serum levels. As compared to the control group, there were no statistically significant group differences in the mean amplitude, phase, or duration of the nighttime melatonin elevation.

  18. New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

    OpenAIRE

    Vigo DE; Vidal MF; Cardinali DP

    2012-01-01

    Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is...

  19. Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters

    DEFF Research Database (Denmark)

    Ansel, L; Bolborea, M; Bentsen, A H

    2010-01-01

    ). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids...

  20. Gut Melatonin in Vertebrates: Chronobiology and Physiology

    Directory of Open Access Journals (Sweden)

    Dr. Saumen Kumar Maitra

    2015-07-01

    Full Text Available Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light-dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light-dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non-photic cue(s as its synchronizer. Based on mammalian findings, physiological significance of gut derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini-review is to summarize existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish.

  1. Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

    Science.gov (United States)

    Dauchy, Robert T.; Xiang, Shulin; Mao, Lulu; Brimer, Samantha; Wren, Melissa A.; Yuan, Lin; Anbalagan, Muralidharan; Hauch, Adam; Frasch, Tripp; Rowan, Brian G.; Blask, David E.; Hill, Steven M.

    2014-01-01

    Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to anti-estrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of ERα+ MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speeds the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characters were not produced in animals where circadian rhythms were not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to re-establish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. PMID:25062775

  2. Ethanol consumption and pineal melatonin daily profile in rats.

    Science.gov (United States)

    Peres, Rafael; do Amaral, Fernanda Gaspar; Madrigrano, Thiago Cardoso; Scialfa, Julieta Helena; Bordin, Silvana; Afeche, Solange Castro; Cipolla-Neto, José

    2011-10-01

    It is well known that melatonin participates in the regulation of many important physiological functions such as sleep-wakefulness cycle, motor coordination and neural plasticity, and cognition. However, as there are contradictory results regarding the melatonin production diurnal profile under alcohol consumption, the aim of this paper was to study the phenomenology and mechanisms of the putative modifications on the daily profile of melatonin production in rats submitted to chronic alcohol intake. The present results show that rats receiving 10% ethanol in drinking water for 35 days display an altered daily profile of melatonin production, with a phase delay and a reduction in the nocturnal peak. This can be partially explained by a loss of the daily rhythm and the 25% reduction in tryptophan hydroxylase activity and, mainly, by a phase delay in arylalkylamine N-acetyltransferase gene expression and a 70% reduction in its peak activity. Upstream in the melatonin synthesis pathway, the results showed that noradrenergic signaling is impaired as well, with a decrease in β1 and α1 adrenergic receptors' mRNA contents and in vitro sustained loss of noradrenergic-stimulated melatonin production by glands from alcohol-treated rats. Together, these results confirm the alterations in the daily melatonin profile of alcoholic rats and suggest the possible mechanisms for the observed melatonin synthesis modification. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  3. Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Hansen, H P; Jacobsen, P

    1999-01-01

    AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity...... (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly...... constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably...

  4. Plasma melatonin circadian rhythm disturbances during pregnancy and postpartum in depressed women and women with personal or family histories of depression.

    Science.gov (United States)

    Parry, Barbara L; Meliska, Charles J; Sorenson, Diane L; Lopez, Ana M; Martinez, Luis F; Nowakowski, Sara; Elliott, Jeffrey A; Hauger, Richard L; Kripke, Daniel F

    2008-12-01

    The purpose of this study was to test the hypothesis that disturbances in levels of plasma melatonin differentiate pregnant and postpartum women with major depression from matched pregnant and postpartum healthy comparison women. Participants were 25 pregnant women (10 with major depression, 15 healthy) and 24 postpartum women (13 with major depression, 11 healthy). Healthy comparison women were matched on the number of weeks pregnant or postpartum. Plasma melatonin levels for each subject were measured every 30 minutes, in dim light (melatonin levels were log-transformed, and calculations were determined for the following measures: baseline and synthesis onset and offset times, duration, peak concentration, and area under the curve. Groups were compared by analyses of covariance, with age, number of weeks pregnant or postpartum, breast-feeding status, and body mass index as covariates. Morning melatonin levels from 2:00 a.m. to 11:00 a.m. were significantly lower in pregnant women with major depression relative to healthy pregnant women. However, these levels were significantly higher in postpartum women with major depression across time intervals relative to postpartum healthy women. Pregnant but not postpartum women with a personal or family history of depression, regardless of their current diagnosis, had significantly earlier melatonin synthesis and baseline offset times relative to women without a family history of depression. In pregnant healthy women but not pregnant women with major depression, melatonin levels increased during the course of pregnancy. This association was not found among postpartum women with major depression or postpartum healthy women. Plasma nocturnal melatonin concentrations, particularly during morning hours, were lower in depressed pregnant women but elevated in depressed postpartum women relative to matched healthy comparison women. In addition, melatonin timing measures were advanced in pregnant women with a personal or family

  5. Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.

    Science.gov (United States)

    de Almeida-Paula, Lidiana Duarte; Costa-Lotufo, Leticia V; Silva Ferreira, Zulma; Monteiro, Amanda Elisa G; Isoldi, Mauro Cesar; Godinho, Rosely O; Markus, Regina P

    2005-11-21

    Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and chick retina imposing a diurnal variation in functional responses [Markus, R.P., Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18-22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S., Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine receptors expressed in plasma membrane. In addition, these cells expressed melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However, the pharmacological profile of melatonin analogs regarding the reduction in cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not point to a mechanism mediated by activation of G(i)-protein coupled receptors. On the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a similar manner both effects. Considering that one isoform of adenylyl cyclase present in rat myotubes is regulated by Ca2+/calmodulin, we propose that melatonin modulates the number of nicotinic acetylcholine receptors via reduction in cyclic AMP accumulation.

  6. New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

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    Vigo DE

    2012-10-01

    Full Text Available Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used. Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow-release melatonin preparations. A prolonged-release preparation of melatonin 2 mg (Circadin® has been approved for the treatment of primary insomnia in patients aged ≥55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo

  7. The therapeutic potential of melatonin on neuronal function during ...

    African Journals Online (AJOL)

    (i.e. arms) in the Elevated plus Maze (EPM) task is shown in fig. 2a, 2b, 2c, and 2d. Melatonin ... Early melatonin intervention before rats reach old age is therefore .... Melanogaster by long-term supplementation with melatonin. Exp Gerontol;37 ...

  8. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    Science.gov (United States)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  9. Relationship between nocturnal serotonin surge and melatonin onset in rodent pineal gland

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    Borjigin Jimo

    2006-09-01

    Full Text Available Abstract Background We have recently reported dynamic circadian rhythms of serotonin (5-HT, 5-hydroxytryptamine output in the pineal gland of rat, which precedes the onset of N-acetylserotonin (NAS and melatonin secretion at night. The present study was aimed at investigating in detail the relationship between 5-HT onset (5HT-on and melatonin onset (MT-on in multiple strains of rats and comparing them with those of hamsters. Methods Animals were maintained in chambers equipped with light (250 lux at cage levels and ventilation in a temperature-controlled room. Following surgical implantation of a microdialysis probe in the pineal gland, animals were individually housed for on-line pineal microdialysis and for automated HPLC analysis of 5-HT and melatonin. Animals were under a light-dark cycle of 12:12 h for the duration of the experiments. Results All animals displayed dynamic 5-HT and melatonin rhythms at night. In all cases, 5HT-on (taken at 80% of the daily maximum levels preceded MT-on (taken at 20% of the daily maximum levels. Within the same animals, 5HT-on as well as MT-on across multiple circadian cycles exhibited minimum variations under entrained conditions. Large inter-individual variations of both 5HT-on and MT-on were found in outbred rats and hamsters under entrained conditions. In comparison, inbred rats displayed very small individual variations of 5HT-on and MT-on. Importantly, we have uncovered a species-specific relationship of 5HT-on and MT-on. 5HT-on of rats, regardless of the strain, preceded MT-on of the same rats by 50 min. In contrast, 5HT-on of hamsters led MT-on by as much as 240 min. Thus, while a constant relationship of 5HT-on and MT-on exists for animals of the same species, the relative timings of 5HT-on and MT-on differ between animals of different species. Conclusion These results suggest that both 5-HT and melatonin could serve as reliable markers of the circadian clock because of their day-to-day precision of

  10. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

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    Svetlana Vladimirovna Prokhorova

    2015-01-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  11. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition

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    Waller KL

    2016-01-01

    Full Text Available Katja Linda Waller,1,2 Erik Lykke Mortensen,2,3 Kirsten Avlund,2,3,†, Merete Osler,3,4 Birgitte Fagerlund,5 Martin Lauritzen,2,6 Steen Gammeltoft,7 Poul Jennum1,2 1Danish Center for Sleep Medicine, Clinic of Clinical Neurophysiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 3Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4Research Center for Prevention and Health, Rigshospitalet, Glostrup, Denmark; 5Center for Neuropsychiatric Schizophrenia Research (CNSR, Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS, Mental Health Center Glostrup, Glostrup, Denmark; 6Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark; 7Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark †Kirsten Avlund passed away on June 15, 2012 Abstract: Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006. The 24

  12. The timing of the shrew: continuous melatonin treatment maintains youthful rhythmic activity in aging Crocidura russula.

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    Elodie Magnanou

    2009-06-01

    Full Text Available Laboratory conditions nullify the extrinsic factors that determine the wild expected lifespan and release the intrinsic or potential lifespan. Thus, wild animals reared in a laboratory often show an increased lifespan, and consequently an increased senescence phase. Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system. The time-keeping hormone melatonin, an important chemical player in this system, is suspected to have an anti-aging role. The Greater White-toothed shrew Crocidura russula is an ideal study model to address questions related to aging and associated changes in biological functions: its lifespan is short and is substantially increased in captivity; daily and seasonal rhythms, while very marked the first year of life, are dramatically altered during the senescence process which starts during the second year. Here we report on an investigation of the effects of melatonin administration on locomotor activity of aging shrews.1 The diel fluctuations of melatonin levels in young, adult and aging shrews were quantified in the pineal gland and plasma. In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2 Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all. In non-implanted and sham-implanted shrews, the rhythm was well marked in adults. A marked degradation in both period and amplitude, however, started after the age of 14-16 months. This pattern was considerably delayed in melatonin-implanted shrews who maintained the daily rhythm for significantly longer.This is the first long term study (>500 days observation of the same individuals that investigates the effects of

  13. Pre-treatment with melatonin decreases abamectin induced toxicity in a nocturnal insect Spodoptera litura (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Subala, Subramanian P; Zubero, Eduardo E; Alatorre-Jimenez, Moises A; Shivakumar, Muthugounder S

    2017-12-01

    Oxidative stress is an important component of the mechanism of pesticide toxicity. The aim of the present study was to investigate the time-dependent melatonin effects against abamectin-induced oxidative stress in a S.litura model. Larvae were divided into 5 different groups; (1) control group,(2) Melatonin group (4.3×10 -5 M/100ml diet), (3) Abamectin group 1.5ml/L, (4) Pre-melatonin treated group (PM) (4.3×10 -5 M/100ml diet) before abamectin exposure 1.5ml/L, (5) Post-melatonin treated group (TM) after abamectin exposure. Melatonin was supplemented via artificial diet in PM and TM animals during 24h. Midgut, fatbody, and hemolymph, were collected for the analysis of oxidative stress markers (Total ROS, GSH, nitrite, TBARS, LPO), antioxidant enzyme levels (SOD, GST, CAT, POX, APOX) in fifth instar larvae. Midgut damage was examined by using morphological analysis. Our results observed that ABA group showed significant changes (pmelatonin. Significant (pmelatonin treatment reduces this damage due to its antioxidant properties, especially POX levels in midgut, fatbody, and hemolymph. Therefore, indoleamine can play a vital role curtailing the abamectin toxicity in time dependent manner in S.litura. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Artificial light pollution: Shifting spectral wavelengths to mitigate physiological and health consequences in a nocturnal marsupial mammal.

    Science.gov (United States)

    Dimovski, Alicia M; Robert, Kylie A

    2018-05-02

    The focus of sustainable lighting tends to be on reduced CO 2 emissions and cost savings, but not on the wider environmental effects. Ironically, the introduction of energy-efficient lighting, such as light emitting diodes (LEDs), may be having a great impact on the health of wildlife. These white LEDs are generated with a high content of short-wavelength 'blue' light. While light of any kind can suppress melatonin and the physiological processes it regulates, these short wavelengths are potent suppressors of melatonin. Here, we manipulated the spectral composition of LED lights and tested their capacity to mitigate the physiological and health consequences associated with their use. We experimentally investigated the impact of white LEDs (peak wavelength 448 nm; mean irradiance 2.87 W/m 2 ), long-wavelength shifted amber LEDs (peak wavelength 605 nm; mean irradiance 2.00 W/m 2 ), and no lighting (irradiance from sky glow light treatments. White LED exposed wallabies had significantly suppressed nocturnal melatonin compared to no light and amber LED exposed wallabies, while there was no difference in lipid peroxidation. Antioxidant capacity declined from baseline to week 10 under all treatments. These results provide further evidence that short-wavelength light at night is a potent suppressor of nocturnal melatonin. Importantly, we also illustrate that shifting the spectral output to longer wavelengths could mitigate these negative physiological impacts. © 2018 Wiley Periodicals, Inc.

  15. Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

    Science.gov (United States)

    Wikner, J; Hirsch, U; Wetterberg, L; Röjdmark, S

    1998-08-01

    Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)--affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients. Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means. The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05). Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

  16. The melatonin receptor agonist ramelteon effectively treats insomnia and behavioral symptoms in autistic disorder.

    Science.gov (United States)

    Kawabe, Kentaro; Horiuchi, Fumie; Oka, Yasunori; Ueno, Shu-Ichi

    2014-01-01

    Children with autism spectrum disorders (ASD), including autistic disorder, frequently suffer from comorbid sleep problems. An altered melatonin rhythm is considered to underlie the impairment in sleep onset and maintenance in ASD. We report three cases with autistic disorder in whom nocturnal symptoms improved with ramelteon, a selective melatonin receptor agonist. Insomnia and behavior, assessed using the Clinical Global Impression-Improvement Scale, improved in two cases with 2 mg ramelteon and in the third case with 8 mg ramelteon. Our findings demonstrate that ramelteon is effective not only for insomnia, but for behavioral problems as well, in patients with autistic disorder.

  17. Independence of circadian entrainment state and responses to melatonin in male Siberian hamsters

    Directory of Open Access Journals (Sweden)

    Gorman Michael R

    2003-10-01

    Full Text Available Abstract Background Seasonal fluctuations in physiology and behavior depend on the duration of nocturnal melatonin secretion programmed by the circadian system. A melatonin signal of a given duration, however, can elicit different responses depending on whether an animal was previously exposed to longer or shorter photoperiod signals (i.e., its photoperiodic history. This report examined in male Siberian hamsters which of two aspects of photoperiod history – prior melatonin exposure or entrainment state of the circadian system – is critical for generating contingent responses to a common photoperiodic signal. Results In Experiment #1, daily melatonin infusions of 5 or 10 h duration stimulated or inhibited gonadal growth, respectively, but had no effect on entrainment of the locomotor activity rhythm to long or short daylengths, thereby demonstrating that melatonin history and entrainment status could be experimentally dissociated. These manipulations were repeated in Experiment #2, and animals were subsequently exposed to a 12 week regimen of naturalistic melatonin signals shown in previous experiments to reveal photoperiodic history effects. Gonadal responses differed as a function of prior melatonin exposure but were unaffected by the circadian entrainment state. Experiment #3 demonstrated that a new photoperiodic history could be imparted during four weeks of exposure to long photoperiods. This effect, moreover, was blocked in animals treated concurrently with constant release melatonin capsules that obscured the endogenous melatonin signal: Following removal of the implants, the gonadal response depended not on the immediately antecedent circadian entrainment state, but on the more remote photoperiodic conditions prior to the melatonin implant. Conclusions The interpretation of photoperiodic signals as a function of prior conditions depends specifically on the history of melatonin exposure. The photoperiodic regulation of circadian

  18. Analysis of the informativeness of melatonin evaluation in polycystic ovary syndrome

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    Elena Andreeva

    2016-12-01

    Full Text Available Background. Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women of reproductive age. Recently, the role of melatonin in the pathogenesis of this syndrome became widely discussed among the scientists, because there is an evidence of its impact on the reproductive function and maturation of oocytes. Aim. To study a informativeness of melatonin determination and its relationship with sleep disorders in PCOS. Materials and methods. The study involved 120 women aged 17–35 years: 60 patients with PCOS and 60 women without this disorder as controls. The level of melatonin in the blood, saliva and its metabolite in urine – 6 sulfatoximelatonin were analyzed. To identify sleep disorders survey was conducted using a questionnaire scoring subjective sleep characteristics. Results. Sleep disorders based on subjective scoring profiles sleep characteristics were identified in PCOS group (up to 70% of patients regardless of BMI. The level of 6-sulfatoximelatonin in urine, nocturnal melatonin levels in saliva (at 3:00 AM and melatonin in the blood were significantly higher in patients with PCOS compared with the control group regardless of BMI. The level of melatonin in follicular fluid was lower in patients with PCOS. There was a significant correlation of melatonin levels in the blood and the degree of sleep disorders according to the questionnaire scoring subjective sleep characteristics, the level of melatonin in saliva at 3:00 AM and a 6-sulfatoximelatonin in daily urine (p = 0.046. Conclusions. PCOS is polyetiology disease, and an important role in the formation and progression in which plays melatonin. Correlation of levels of this hormone in different body fluids suggests its systemic action and direct involvement in the regulation of reproductive function.

  19. Melatonin, mitochondria, and the metabolic syndrome.

    Science.gov (United States)

    Cardinali, Daniel P; Vigo, Daniel E

    2017-11-01

    A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

  20. Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

    Science.gov (United States)

    Tan, Dun-Xian; Manchester, Lucien C.; Qin, Lilan; Reiter, Russel J.

    2016-01-01

    Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria. PMID:27999288

  1. Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night.

    Science.gov (United States)

    Kozaki, Tomoaki; Kubokawa, Ayaka; Taketomi, Ryunosuke; Hatae, Keisuke

    2015-07-04

    Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS. Twelve male subjects between the ages of 19 and 23 years (mean ± S.D., 20.8 ± 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30). A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions. Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls.

  2. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Science.gov (United States)

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  3. MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH

    Directory of Open Access Journals (Sweden)

    Russel J REITER; Fatih GULTEKIN; Luis J FLORES; Ma Pilar TERRON; Dun-Xian TAN

    2006-04-01

    Full Text Available This review summarizes the beneficial actions of melatonin in various experimental conditions/diseases and identifies where the use of melatonin may be helpful in improving public health. The nightly use of melatonin supplements by humans often improves their sleep and helps correct the circadian dyssynchronization associated with “jet lag”. Additionally, melatonin has been found effective in curtailing the growth of a variety of experimental cancers. Mechanistically, this is achieved by melatonin’s ability to limit fatty acid uptake, especially linoleic acid, by tumor cells. Fatty acids are growth factors for many tumors. Additionally, melatonin inhibits the elevated telomerase activity of tumor cells thus making them more fragile and vulnerable to chemotherapies. Melatonin also may inhibit angiogenesis in tumors by suppressing endothelin-1 production and the indole interferes with the stimulatory action of steroids on hormone-responsive tumors. As an ubiquitously-acting antioxidant, melatonin reduces cardiac damage during ischemia/reperfusion (I/R injury (heart attack and during I/R to the brain (stroke. Melatonin also limits the toxicity of amyloid  peptide and of neurofibrillary tangles, two of the cardinal signs of Alzheimer’s disease. Collectively, these data suggest supplementation with melatonin, whose endogenous levels decrease with age, may improve the quality of life in the aged and, as a consequence, be beneficial for public health generally. [TAF Prev Med Bull 2006; 5(2.000: 131-158

  4. Effect of day/night administration of three different inhalational anesthetics on melatonin levels in rats.

    Science.gov (United States)

    Ocmen, Elvan; Erdost, Hale Aksu; Duru, Leyla S; Akan, Pinar; Cimrin, Dilek; Gokmen, Ali N

    2016-06-01

    The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 am and 1:00 pm (day groups) or 7:00 pm and 1:00 am (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17±12.95 for control, 59.79±27.83 for isoflurane, 50.75±34.28 for sevoflurane and 212.20±49.56 pg/mL for desflurane groups. The night groups' mean melatonin levels were 136.12±33.20 for control, 139.85±56.29 for isoflurane, 117.48±82.39 for sevoflurane and 128.70±44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 am and 1:00 pm significantly increased melatonin levels (p0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p=0.718 and p>0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia. Copyright © 2016. Published by Elsevier Taiwan.

  5. Detection of Nighttime Melatonin Level in Chinese Original Quiet Sitting

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    Chien-Hui Liou

    2010-10-01

    Conclusion: Our results support the hypothesis that meditation might elevate the nighttime salivary melatonin levels. It suggests that COQS can be used as a psychophysiological stimulus to increase endogenous secretion of melatonin, which in turn, might contribute to an improved sense of well-being.

  6. Melatonin inhibits endothelin-1 and induces endothelial nitric oxide ...

    African Journals Online (AJOL)

    Although, I/R augmented the endothelin-1 (ET-1) gene expression and the level of big endothelin-1 (big ET-1) in liver tissue, melatonin attenuated these increases. Conversely, non-significant decrease in endothelial nitric oxide synthase (eNOS) mRNA expression in I/R group was significantly elevated by melatonin in ...

  7. Exogenous melatonin administration modifies cutaneous vasoconstrictor response to whole body skin cooling in humans.

    Science.gov (United States)

    Aoki, Ken; Zhao, Kun; Yamazaki, Fumio; Sone, Ryoko; Alvarez, Guy E; Kosiba, Wojciech A; Johnson, John M

    2008-03-01

    Humans and other diurnal species experience a fall in internal temperature (T(int)) at night, accompanied by increased melatonin and altered thermoregulatory control of skin blood flow (SkBF). Also, exogenous melatonin induces a fall in T(int), an increase in distal skin temperatures and altered control of the cutaneous active vasodilator system, suggesting an effect of melatonin on the control of SkBF. To test whether exogenous melatonin also affects the more tonically active vasoconstrictor system in glabrous and nonglabrous skin during cooling, healthy males (n = 9) underwent afternoon sessions of whole body skin temperature (T(sk)) cooling (water-perfused suits) after oral melatonin (Mel; 3 mg) or placebo (Cont). Cutaneous vascular conductance (CVC) was calculated from SkBF (laser Doppler flowmetry) and non-invasive blood pressure. Baseline T(int) was lower in Mel than in Cont (P forearm CVC was first significantly reduced at T(sk) of 34.33 +/- 0.01 degrees C (P forearm CVC in Mel was significantly less than in Cont at T(sk) of 32.66 +/- 0.01 degrees C and lower (P < 0.05). In Mel, palmar CVC was significantly higher than in Cont above T(sk) of 33.33 +/- 0.01 degrees C, but not below. Thus exogenous melatonin blunts reflex vasoconstriction in nonglabrous skin and shifts vasoconstrictor system control to lower T(int). It provokes vasodilation in glabrous skin but does not suppress the sensitivity to falling T(sk). These findings suggest that by affecting the vasoconstrictor system, melatonin has a causal role in the nocturnal changes in body temperature and its control.

  8. Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

    Directory of Open Access Journals (Sweden)

    Maria Angeles Bonmati-Carrion

    2014-12-01

    Full Text Available Currently, in developed countries, nights are excessively illuminated (light at night, whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD, including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system.

  9. Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-KV Transmission Line

    Science.gov (United States)

    Lee, Jack Monroe, Jr.

    There is ongoing controversy about the possibility of adverse biological effects from environmental exposures to electric and magnetic fields. These fields are produced by all electrical equipment and appliances including electrical transmission lines. The objective of this environmental science study was to investigate the possible effects of a high voltage transmission line on domestic sheep (Ovis aries L.), a species that can often be found near such lines. The study was primarily designed to determine whether a specific effect of electric and magnetic fields found in laboratory animals also occurs in livestock under natural environmental conditions. The effect is the ability of fields, at levels found in the environment, to significantly depress the normally high nocturnal concentrations of the pineal hormone-melatonin. Ten female Suffolk lambs were penned for 10 months directly beneath a 500-kV transmission line near Estacada, Oregon. Ten other lambs of the same type were penned in a control area away from the transmission line where electric and magnetic fields were at ambient levels. Serum melatonin was analyzed by radioimmunoassay (RIA) from 6618 blood samples collected at 0.5 to 3-hour intervals over eight 48-hour periods. Serum progesterone was analyzed by RIA from blood samples collected twice weekly. Serum cortisol was also assayed by RIA from the blood samples collected during the 48-hour samples. Results showed that lambs in both the control and line groups had the typical pattern of melatonin secretion consisting of low daytime and high nighttime serum concentrations. There were no statistically significant differences between groups in melatonin levels, or in the phase or duration of the nighttime melatonin elevation. Age at puberty and number of reproductive cycles also did not differ between groups. Serum cortisol showed a circadian rhythm with highest concentrations during the day. There were, however, no differences in cortisol concentrations

  10. Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases.

    Science.gov (United States)

    Smolensky, Michael H; Sackett-Lundeen, Linda L; Portaluppi, Francesco

    2015-01-01

    Routine exposure to artificial light at night (ALAN) in work, home, and community settings is linked with increased risk of breast and prostate cancer (BC, PC) in normally sighted women and men, the hypothesized biological rhythm mechanisms being frequent nocturnal melatonin synthesis suppression, circadian time structure (CTS) desynchronization, and sleep/wake cycle disruption with sleep deprivation. ALAN-induced perturbation of the CTS melatonin synchronizer signal is communicated maternally at the very onset of life and after birth via breast or artificial formula feedings. Nighttime use of personal computers, mobile phones, electronic tablets, televisions, and the like--now epidemic in adolescents and adults and highly prevalent in pre-school and school-aged children--is a new source of ALAN. However, ALAN exposure occurs concomitantly with almost complete absence of daytime sunlight, whose blue-violet (446-484 nm λ) spectrum synchronizes the CTS and whose UV-B (290-315 nm λ) spectrum stimulates vitamin D synthesis. Under natural conditions and clear skies, day/night and annual cycles of UV-B irradiation drive corresponding periodicities in vitamin D synthesis and numerous bioprocesses regulated by active metabolites augment and strengthen the biological time structure. Vitamin D insufficiency and deficiency are widespread in children and adults in developed and developing countries as a consequence of inadequate sunlight exposure. Past epidemiologic studies have focused either on exposure to too little daytime UV-B or too much ALAN, respectively, on vitamin D deficiency/insufficiency or melatonin suppression in relation to risk of cancer and other, e.g., psychiatric, hypertensive, cardiac, and vascular, so-called, diseases of civilization. The observed elevated incidence of medical conditions the two are alleged to influence through many complementary bioprocesses of cells, tissues, and organs led us to examine effects of the totality of the artificial light

  11. Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects.

    Science.gov (United States)

    Parry, B L; Berga, S L; Mostofi, N; Klauber, M R; Resnick, A

    1997-02-01

    The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2,500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM; 19:00 to 21:00 h), or (3) dim (compressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was decreased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the

  12. Impact of different colours of artificial light at night on melatonin rhythm and gene expression of gonadotropins in European perch.

    Science.gov (United States)

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Kleiner, Wibke; Kloas, Werner

    2016-02-01

    The distribution and intensity of artificial light at night, commonly referred to as light pollution, is consequently rising and progressively also ecological implications come to light. Low intensity light is known to suppress nocturnal melatonin production in several fish species. This study aims to examine the least suppressive light colour for melatonin excreted into the holding water and the influence of different light qualities and quantities in the night on gene expression of gonadotropins in fish. European perch (Perca fluviatilis) were exposed to light of different wavelengths during the night (blue, green, and red). Melatonin concentrations were measured from water samples every 3h during a 24h period. Gene expression of gonadotropins was measured in perch exposed to different light colours and was additionally examined for perch subjected to different intensities of white light (0 lx, 1 lx, 10 lx, 100 lx) during the night. All different light colours caused a significant drop of melatonin concentration; however, blue light was least suppressive. Gene expression of gonadotropins was not influenced by nocturnal light of different light colours, but in female perch gonadotropin expression was significantly reduced by white light already at the lowest level (1 lx). We conclude that artificial light with shorter wavelengths at night is less effective in disturbing biological rhythms of perch than longer wavelengths, coinciding with the light situation in freshwater habitats inhabited by perch. Different light colours in the night showed no significant effect on gonadotropin expression, but white light in the night can disturb reproductive traits already at very low light intensities. These findings indicate that light pollution has not only the potential to disturb the melatonin cycle but also the reproductive rhythm and may therefore have implications on whole species communities. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Melatonin Promotes Superovulation in Sika Deer (Cervus nippon

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2014-07-01

    Full Text Available In this study, the effects of melatonin (MT on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH, luteinizing hormone (LH and PRL were investigated in female sika deer. Different doses (40 or 80 mg/animal of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05. The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05, which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.

  14. Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach.

    Science.gov (United States)

    Srinivasan, Venkataramanujam; Ahmad, Asma H; Mohamed, Mahaneem; Zakaria, Rahimah

    2012-05-01

    Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin

  15. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin......, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized...... to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma...

  16. Identification of genes for melatonin synthetic enzymes in 'Red Fuji' apple (Malus domestica Borkh.cv.Red) and their expression and melatonin production during fruit development.

    Science.gov (United States)

    Lei, Qiong; Wang, Lin; Tan, Dun-Xian; Zhao, Yu; Zheng, Xiao-Dong; Chen, Hao; Li, Qing-Tian; Zuo, Bi-Xiao; Kong, Jin

    2013-11-01

    Melatonin is present in many edible fruits; however, the presence of melatonin in apple has not previously been reported. In this study, the genes for melatonin synthetic enzymes including tryptophan decarboxylase, tryptamine 5-hydroxylase (T5H), arylalkylamine N-acetyltransferase, and N-acetylserotonin methyltransferase were identified in 'Red Fuji' apple. Each gene has several homologous genes. Sequence analysis shows that these genes have little homology with those of animals and they only have limited homology with known genes of rice melatonin synthetic enzymes. Multiple origins of melatonin synthetic genes during the evolution are expected. The expression of these genes is fully coordinated with melatonin production in apple development. Melatonin levels in apple exhibit an inverse relationship with the content of malondialdehyde, a product of lipid peroxidation. Two major melatonin synthetic peaks appeared on July 17 and on October 8 in both unbagged and bagged apple samples. At the periods mentioned above, apples experienced rapid expansion and increased respiration. These episodes significantly elevate reactive oxygen species production in the apple. Current data further confirmed that melatonin produced in apple was used to neutralize the toxic oxidants and protect the developing apple against oxidative stress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Do night-active birds lack daily melatonin rhythms? A case study comparing a diurnal and a nocturnal-foraging gull species

    NARCIS (Netherlands)

    Wikelski, M; Tarlow, EM; Eising, CM; Groothuis, TGG; Gwinner, E; Tarlow, Elisa M.; Groothuis, Ton G.G.; Bairlein, F.

    Plasma melatonin concentrations in most animals investigated so far increase at night regardless of whether individuals are day or night active. Nevertheless, daily melatonin amplitudes are often seasonally adjusted to ecological conditions, with birds that breed at high latitudes and migrate during

  18. Melatonin: a possible link between the presence of artificial light at night and reductions in biological fitness

    Science.gov (United States)

    Jones, Therésa M.; Durrant, Joanna; Michaelides, Ellie B.; Green, Mark P.

    2015-01-01

    The mechanisms underpinning the ecological impacts of the presence of artificial night lighting remain elusive. One suspected underlying cause is that the presence of light at night (LAN) supresses nocturnal production of melatonin, a key driver of biological rhythm and a potent antioxidant with a proposed role in immune function. Here, we briefly review the evidence for melatonin as the link between LAN and changes in behaviour and physiology. We then present preliminary data supporting the potential for melatonin to act as a recovery agent mitigating the negative effects of LAN in an invertebrate. Adult crickets (Teleogryllus commodus), exposed to constant illumination, were provided with dietary melatonin (concentrations: 0, 10 or 100 µg ml−1) in their drinking water. We then compared survival, lifetime fecundity and, over a 4-week period, immune function (haemocyte concentration, lysozyme-like and phenoloxidase (PO) activity). Melatonin supplementation was able only partially to mitigate the detrimental effects of LAN: it did not improve survival or fecundity or PO activity, but it had a largely dose-dependent positive effect on haemocyte concentration and lysozyme-like activity. We discuss the implications of these relationships, as well as the usefulness of invertebrates as model species for future studies that explore the effects of LAN. PMID:25780235

  19. Endogenous melatonin and oxidatively damaged guanine in DNA

    Directory of Open Access Journals (Sweden)

    Poulsen Henrik E

    2009-10-01

    Full Text Available Abstract Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Methods Mother-father-daughter(s families (n = 55 were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight. Results Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR was associated with significantly higher levels of 8-oxodG (p Conclusion Low levels of endogenous melatonin production among older individuals may lead to

  20. Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro.

    Science.gov (United States)

    Wang, Bao-Qiang; Yang, Quan-Hui; Xu, Rong-Kun; Xu, Jian-Ning

    2013-01-01

    Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma. In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods. Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells. There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

  1. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Johnson Cynthia E

    2008-09-01

    Full Text Available Abstract Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD, short day length (L8:D16; SD, and long day length (L16:D8; LD. We compared nocturnality (the proportion of activity during night or subjective night, duration of activity (alpha, activity onset and offset, phase angle of entrainment, and free running rhythms (tau of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non

  2. Metabolic syndrome, its pathophysiology and the role of melatonin.

    Science.gov (United States)

    Srinivasan, Venkataramanujam; Ohta, Yoshiji; Espino, Javier; Pariente, Jose A; Rodriguez, Ana B; Mohamed, Mahaneem; Zakaria, Rahimah

    2013-01-01

    Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

  3. Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells.

    Directory of Open Access Journals (Sweden)

    Tingting Jiang

    Full Text Available Oxidative stress is a contributing factor to the development and progression of diabetic retinopathy, a leading cause of blindness in people at working age worldwide. Recent studies showed that Müller cells play key roles in diabetic retinopathy and produce vascular endothelial growth factor (VEGF that regulates retinal vascular leakage and proliferation. Melatonin is a potent antioxidant capable of protecting variety of retinal cells from oxidative damage. In addition to the pineal gland, the retina produces melatonin. In the current study, we investigated whether melatonin protects against hyperglycemia-induced oxidative injury to Müller cells and explored the potential underlying mechanisms. Our results show that both melatonin membrane receptors, MT1 and MT2, are expressed in cultured primary Müller cells and are upregulated by elevated glucose levels. Both basal and high glucose-induced VEGF production was attenuated by melatonin treatment in a dose-dependent manner. Furthermore, we found that melatonin is a potent activator of Akt in Müller cells. Our findings suggest that in addition to functioning as a direct free radical scavenger, melatonin can elicit cellular signaling pathways that are protective against retinal injury during diabetic retinopathy.

  4. Effect of melatonin on kidney cold ischemic preservation injury

    Science.gov (United States)

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2nd, 24th, 36th, and 48th hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48th hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID:24179573

  5. Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters

    DEFF Research Database (Denmark)

    Ansel, L; Bolborea, M; Bentsen, A H

    2010-01-01

    In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rode......In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs......). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids...... differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters...

  6. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

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    Isabel Cubero-Millán

    2014-09-01

    Full Text Available The vast majority of Attention-deficit/hyperactivity disorder (ADHD patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1 the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2 the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria were divided into subgroups using the “Children’s Depression Inventory” (CDI. Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

  7. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun Xian; Korkmaz, Ahmet; Rosales-Corral, Sergio A

    2014-01-01

    circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus. Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn. To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the fetus. Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions. A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin.

  8. Melatonin

    DEFF Research Database (Denmark)

    Manchester, Lucien C; Coto-Montes, Ana; Boga, Jose Antonio

    2015-01-01

    Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic...... cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later...... in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce...

  9. Nocturnal Eating: Association with Binge Eating, Obesity, and Psychological Distress

    Science.gov (United States)

    Striegel-Moore, Ruth H.; Rosselli, Francine; Wilson, G. Terence; Perrin, Nancy; Harvey, Kate; DeBar, Lynn

    2009-01-01

    Objective To examine clinical correlates of nocturnal eating, a core behavioral symptom of night eating syndrome. Method Data from 285 women who had participated in a two-stage screening for binge eating were utilized. Women (n = 41) who reported one or more nocturnal eating episodes in the past 28 days on the Eating Disorder Examination and women who did not report nocturnal eating (n =244) were compared on eating disorder symptomatology, Body Mass Index (BMI), and on measures of psychosocial adjustment. Results Nocturnal eaters were significantly more likely to report binge eating and differed significantly from non-nocturnal eaters (with responses indicating greater disturbance) on weight and shape concern, eating concern, self-esteem, depression, and functional impairment, but not on BMI or dietary restraint. Group differences remained significant in analyses adjusting for binge eating. Conclusions This study confirms the association between nocturnal eating and binge eating previously found in treatment seeking samples yet also suggests that the elevated eating disorder symptoms and decreased psychosocial adjustment observed in nocturnal eaters is not simply a function of binge eating. PMID:19708071

  10. Melatonin Inhibits GnRH-1, GnRH-3 and GnRH Receptor Expression in the Brain of the European Sea Bass, Dicentrarchus labrax

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    José Antonio Muñoz-Cueto

    2013-04-01

    Full Text Available Several evidences supported the existence of melatonin effects on reproductive system in fish. In order to investigate whether melatonin is involved in the modulation of GnRH systems in the European sea bass, we have injected melatonin (0.5 µg/g body mass in male specimens. The brain mRNA transcript levels of the three GnRH forms and the five GnRH receptors present in this species were determined by real time quantitative PCR. Our findings revealed day–night variations in the brain expression of GnRH-1, GnRH-3 and several GnRH receptors (dlGnRHR-II-1c, -2a, which exhibited higher transcript levels at mid-light compared to mid-dark phase of the photocycle. Moreover, an inhibitory effect of melatonin on the nocturnal expression of GnRH-1, GnRH-3, and GnRH receptors subtypes 1c, 2a and 2b was also demonstrated. Interestingly, the inhibitory effect of melatonin affected the expression of hypophysiotrophic GnRH forms and GnRH receptors that exhibit day–night fluctuations, suggesting that exogenous melatonin reinforce physiological mechanisms already established. These interactions between melatoninergic and GnRH systems could be mediating photoperiod effects on reproductive and other rhythmic physiological events in the European sea bass.

  11. Influence of light intensity and spectral composition of artificial light at night on melatonin rhythm and mRNA expression of gonadotropins in roach Rutilus rutilus.

    Science.gov (United States)

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Kleiner, Wibke; Kloas, Werner

    2018-02-01

    In this study we investigated the influence of artificial light at night (ALAN) of different intensities (0, 1, 10, 100 lx) and different colours (blue, green, red) on the daily melatonin rhythm and mRNA expression of gonadotropins in roach Rutilus rutilus, a ubiquitous cyprinid, which occur in standing and moderately flowing freshwater habitats of central Europe. Melatonin concentrations were significantly lowered under nocturnal white light already at 1 lx. Low intensity blue, green and red ALAN lowered the melatonin levels significantly in comparison to a dark control. We conclude that ALAN can disturb melatonin rhythms in roach at very low intensities and at different wavelengths and thus light pollution in urban waters has the potential to impact biological rhythms in fish. However, mRNA expression of gonadotropins was not affected by ALAN during the period of the experiments. Thus, suspected implications of ALAN on reproduction of roach could not be substantiated.

  12. Natural Variation in Banana Varieties Highlights the Role of Melatonin in Postharvest Ripening and Quality.

    Science.gov (United States)

    Hu, Wei; Yang, Hai; Tie, Weiwei; Yan, Yan; Ding, Zehong; Liu, Yang; Wu, Chunlai; Wang, Jiashui; Reiter, Russel J; Tan, Dun-Xian; Shi, Haitao; Xu, Biyu; Jin, Zhiqiang

    2017-11-22

    This study aimed to investigate the role of melatonin in postharvest ripening and quality in various banana varieties with contrasting ripening periods. During the postharvest life, endogenous melatonin showed similar performance with ethylene in connection to ripening. In comparison to ethylene, melatonin was more correlated with postharvest banana ripening. Exogenous application of melatonin resulted in a delay of postharvest banana ripening. Moreover, this effect is concentration-dependent, with 200 and 500 μM treatments more effective than the 50 μM treatment. Exogenous melatonin also led to elevated endogenous melatonin content, reduced ethylene production through regulation of the expression of MaACO1 and MaACS1, and delayed sharp changes of quality indices. Taken together, this study highlights that melatonin is an indicator for banana fruit ripening in various varieties, and the repression of ethylene biosynthesis and postharvest ripening by melatonin can be used for biological control of postharvest fruit ripening and quality.

  13. Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus

    Science.gov (United States)

    Campbell, J. Fallon; Swartz, Sarah J.; Wenderfer, Scott E.

    2015-01-01

    Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus ( p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus ( p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated

  14. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

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    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  15. The effect of melatonin on eye lens of rats exposed to ultraviolet radiation.

    Science.gov (United States)

    Anwar, M M; Moustafa, M A

    2001-05-01

    We investigated the influence of exogenously administered melatonin on adult rats eye lenses exposed to ultraviolet radiation (UV) A and B ranging from 356-254 nm irradiation at 8 microW/cm(2). Rats exposed to this range of UV for 15 min for one week showed a significant (PUV-radiation significantly (PUV irradiation, may be the main cause of lens opacification. Melatonin injection with radiation significantly reduced (Pradiation, SOD and GSH-Px enzyme activities increased significantly (PUV radiation was as effective as melatonin treatment concurrent with UV irradiation. We conclude that melatonin may protect the eye lens from the damaging effects of UV exposure, and its actions protect lens from oxidative stress, elevating Ca(2+) levels, which are considered as an important causes of cataractogenesis.

  16. Melatonin in Plants - Diversity of Levels and Multiplicity of Functions.

    Science.gov (United States)

    Hardeland, Rüdiger

    2016-01-01

    Melatonin has been detected in numerous plant species. A particularly surprising finding concerns the highly divergent levels of melatonin that vary between species, organs and environmental conditions, from a few pg/g to over 20 μg/g, reportedly up to 200 μg/g. Highest values have been determined in oily seeds and in plant organs exposed to high UV radiation. The divergency of melatonin concentrations is discussed under various functional aspects and focused on several open questions. This comprises differences in precursor availability, catabolism, the relative contribution of isoenzymes of the melatonin biosynthetic pathway, and differences in rate limitation by either serotonin N-acetyltransferase or N-acetylserotonin O-methyltransferase. Other differences are related to the remarkable pleiotropy of melatonin, which exhibits properties as a growth regulator and morphogenetic factor, actually debated in terms of auxin-like effects, and as a signaling molecule that modulates pathways of ethylene, abscisic, jasmonic and salicylic acids and is involved in stress tolerance, pathogen defense and delay of senescence. In the context of high light/UV intensities, elevated melatonin levels exceed those required for signaling via stress-related phytohormones and may comprise direct antioxidant and photoprotectant properties, perhaps with a contribution of its oxidatively formed metabolites, such as N (1)-acetyl-N (2)-formyl-5-methoxykynuramine and its secondary products. High melatonin levels in seeds may also serve antioxidative protection and have been shown to promote seed viability and germination capacity.

  17. Melatonin and the electron transport chain.

    Science.gov (United States)

    Hardeland, Rüdiger

    2017-11-01

    Melatonin protects the electron transport chain (ETC) in multiple ways. It reduces levels of ·NO by downregulating inducible and inhibiting neuronal nitric oxide synthases (iNOS, nNOS), thereby preventing excessive levels of peroxynitrite. Both ·NO and peroxynitrite-derived free radicals, such as ·NO 2 , hydroxyl (·OH) and carbonate radicals (CO 3 · - ) cause blockades or bottlenecks in the ETC, by ·NO binding to irons, protein nitrosation, nitration and oxidation, changes that lead to electron overflow or even backflow and, thus, increased formation of superoxide anions (O 2 · - ). Melatonin improves the intramitochondrial antioxidative defense by enhancing reduced glutathione levels and inducing glutathione peroxidase and Mn-superoxide dismutase (Mn-SOD) in the matrix and Cu,Zn-SOD in the intermembrane space. An additional action concerns the inhibition of cardiolipin peroxidation. This oxidative change in the membrane does not only initiate apoptosis or mitophagy, as usually considered, but also seems to occur at low rate, e.g., in aging, and impairs the structural integrity of Complexes III and IV. Moreover, elevated levels of melatonin inhibit the opening of the mitochondrial permeability transition pore and shorten its duration. Additionally, high-affinity binding sites in mitochondria have been described. The assumption of direct binding to the amphipathic ramp of Complex I would require further substantiation. The mitochondrial presence of the melatonin receptor MT 1 offers the possibility that melatonin acts via an inhibitory G protein, soluble adenylyl cyclase, decreased cAMP and lowered protein kinase A activity, a signaling pathway shown to reduce Complex I activity in the case of a mitochondrial cannabinoid receptor.

  18. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

    Directory of Open Access Journals (Sweden)

    Gillian W Reierson

    2009-09-01

    Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT, the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC and degraded by phosphodiesterases (PDEs. Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

  19. Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury.

    Science.gov (United States)

    Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Rulli, Immacolata; Salvo, Vincenzo; Buonocore, Giuseppe; Reiter, Russel J; Gitto, Eloisa

    2017-05-13

    Traumatic brain injury (TBI) is a leading cause of death and disability in children. Oxidative stress plays a significant role in brain damage and melatonin exhibits both direct and indirect antioxidant effects. The primary aim of the present study was to evaluate serum melatonin levels in children with severe TBI in comparison to critically ill children admitted to the Pediatric Intensive Care Unit for conditions other than TBI. Twenty-four children were evaluated, equally divided into severe TBI and no-TBI. Blood samples for serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and 12:00. Mean serum melatonin peaks in children of the TBI group were higher compared to the values of no-TBI critically ill children (495 ± 102 vs. 294 ± 119 pg/mL, p = 0.0002). Furthermore, the difference was even more significant in comparison to values reported in literature for healthy age-matched children (495 ± 102 vs. 197 ± 71 pg/mL, p melatonin levels dramatically increase in children after severe TBI. This elevation is likely to represent a response to oxidative stress and/or inflammation due to severe head injury.

  20. Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

    Science.gov (United States)

    Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

    2017-09-01

    This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

  1. Effects of evening light conditions on salivary melatonin of Japanese junior high school students

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    Harada Tetsuo

    2004-08-01

    Full Text Available Abstract Background In a previous study, when adult subjects were exposed to a level of 400 lux light for more than 30 min or a level of 300 lux light for more than 2 hours, salivary melatonin concentration during the night dropped lower than when the subjects were exposed to dim illumination. It was suggested that such light exposure in adolescents or children during the first half of subjective night in normal life might decrease the melatonin level and prevent the falling into sleep. However, there has been no actual study on the effects of light exposure in adolescents. Methods Effects of exposure to the bright light (2000 lux from fluorescent light bulbs during a period of three hours from 19:30 to 22:30 in one evening were examined on evening salivary melatonin concentrations from 19:45 to 23:40. The control group was exposed to dim light (60 lux during these three hours. Both the dim light control group [DLCG] and the bright light experimental group [BLEG] consisted of two female and three male adolescent participants aged 14–15 y. Results The salivary melatonin level increased rapidly from 3.00 pg/ml at 21:45 to 9.18 pg/ml at 23:40 in DLCG, whereas it remained at less than 1.3 pg/ml for the three hours in BLEG. Melatonin concentration by BLEG at 22:30 of the experimental day was lower than that at the same time on the day before the experimental day, whereas it was significantly higher in the experimental day than on the day before the experimental day in DLCG. Conclusions Bright lights of 2000 lux and even moderate lights of 200–300 lux from fluorescent light bulbs can inhibit nocturnal melatonin concentration in adolescents. Ancient Japanese lighting from a traditional Japanese hearth, oil lamp or candle (20–30 lux could be healthier for children and adolescents because rapid and clear increase in melatonin concentration in blood seems to occur at night under such dim light, thus facilitating a smooth falling into night sleep.

  2. Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

    Directory of Open Access Journals (Sweden)

    M.A. Quera Salva

    2012-04-01

    Full Text Available Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC. Melatonin (N-acetyl-5-hydroxytryptamine is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.

  3. Melatonin.

    Science.gov (United States)

    Hardeland, Rüdiger; Pandi-Perumal, S R; Cardinali, Daniel P

    2006-03-01

    Melatonin, originally discovered as a hormone of the pineal gland, is produced by bacteria, protozoa, plants, fungi, invertebrates, and various extrapineal sites of vertebrates, including gut, skin, Harderian gland, and leukocytes. Biosynthetic pathways seem to be identical. Actions are pleiotropic, mediated by membrane and nuclear receptors, other binding sites or chemical interactions. Melatonin regulates the sleep/wake cycle, other circadian and seasonal rhythms, and acts as an immunostimulator and cytoprotective agent. Circulating melatonin is mostly 6-hydroxylated by hepatic P450 monooxygenases and excreted as 6-sulfatoxymelatonin. Pyrrole-ring cleavage is of higher importance in other tissues, especially the brain. The product, N1-acetyl-N2-formyl-5-methoxykynuramine, is formed by enzymatic, pseudoenzymatic, photocatalytic, and numerous free-radical reactions. Additional metabolites result from hydroxylation and nitrosation. The secondary metabolite, N1-acetyl-5-methoxykynuramine, supports mitochondrial function and downregulates cyclooxygenase 2. Antioxidative protection, safeguarding of mitochondrial electron flux, and in particular, neuroprotection, have been demonstrated in many experimental systems. Findings are encouraging to use melatonin as a sleep promoter and in preventing progression of neurodegenerative diseases.

  4. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  5. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  6. MT1 melatonin receptors and their role in the oncostatic action of melatonin

    Directory of Open Access Journals (Sweden)

    Karolina Danielczyk

    2009-09-01

    Full Text Available Melatonin, the main hormone produced by the pineal gland, strongly inhibits the growth of cancer cells [i]in vitro[/i] and [i]in vivo[/i]. Some publications indicate that the addition of melatonin to culture medium slows the proliferation of some cancer cell lines. It is also suggested that melatonin used as an adjuvant benefits the effectiveness and tolerance of chemotherapy. The mechanisms of this are not fully understood, but melatonin receptors might be one of the most important elements. Two distinct types of membrane-bound melatonin receptors have been identified in humans: MT1 (Mel1a and MT2 (Mel1b receptors. These subtypes are 60�0homologous at the amino-acid level. MT1 receptors are G-protein-coupled receptors. Through the α subunit of G protein, melatonin receptors stimulate an adenylate cyclase and decrease the level of cAMP. This has a significant influence on cell proliferation and has been confirmed in many tests on different cell lines, such as S-19, B-16 murine melanoma cells, and breast cancer cells. It seems that expression of the MT1 melatonin receptors benefits the efficacy of melatonin treatment. Melatonin and its receptors may provide a promising way to establish new alternative therapeutic approaches in human cancer prevention.

  7. Radioimmunoassay for Melatonin

    International Nuclear Information System (INIS)

    Tapp, E.; Skinner, R.G.; Phillips, V.

    1980-01-01

    A radioimmunoassay for melatonin has been developed and used to measure the level of melatonin of male and post-menopausal female patients coming to operation for benign and malignant conditions. The amount of melatonin in the serum of the females was considerably lower than that in males. No difference could be found between patients suffering from benign and malignant conditions. A patient with a non-parenchymatous pineal tumour had considerably lower levels in the serum at three months after surgery and radiotherapy. A further month later melatonin could not be found in samples of serum taken over a 24-hour period. (author)

  8. Utility of melatonin to treat surgical stress after major vascular surgery--a safety study

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens; Nielsen, Hans Jørgen

    2008-01-01

    of reducing oxidative damage. The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre-, intra-, and postoperative period. Six patients undergoing......Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress. As an antioxidant in animal and human studies, melatonin has the potential of ameliorating some of this oxidative stress, but melatonin has never been administered to adults during surgery for the purpose......-reactive protein (CRP) were also measured for 4 days after surgery. Melatonin administration did not change hemodynamic parameters (mean arterial pressure or pulse rate) during surgery (P = 0.499 and 0.149, respectively), but oxidative stress parameters (MDA and AA) decreased significantly (P = 0.014 and 0...

  9. Utility of melatonin to treat surgical stress after major vascular surgery - a safety study

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Lykkesfeldt, Jens; Nielsen, Hans Jørgen

    2008-01-01

    of reducing oxidative damage. The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre-, intra- and postoperative period. Six patients undergoing aortic......Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress. As an antioxidant in animal and human studies, melatonin has the potential of ameliorating some of this oxidative stress, but melatonin has never been administered to adults during surgery for the purpose......) were also measured for four days after surgery. Melatonin administration did not change hemodynamic parameters (mean arterial pressure or pulse rate) during surgery (P=0.499 and 0.149, respectively), but oxidative stress parameters (MDA and AA) decreased significantly (P=0.014 and 0.001, respectively...

  10. Potential utility of melatonin as an antioxidant during pregnancy and in the perinatal period.

    Science.gov (United States)

    Aversa, Salvatore; Pellegrino, Salvatore; Barberi, Ignazio; Reiter, Russel J; Gitto, Eloisa

    2012-03-01

    Reactive oxygen species (ROS) play a critical role in the pathogenesis of various diseases during pregnancy and the perinatal period. Newborns are more prone to oxidative stress than individuals later in life. During pregnancy, increased oxygen demand augments the rate of production of ROS and women, even during normal pregnancies, experience elevated oxidative stress compared with non-pregnant women. ROS generation is also increased in the placenta during preeclampsia. Melatonin is a highly effective direct free-radical scavenger, indirect antioxidant, and cytoprotective agent in human pregnancy and it appears to be essential for successful pregnancy. This suggests a role for melatonin in human reproduction and in neonatal pathologies (asphyxia, respiratory distress syndrome, sepsis, etc.). This review summarizes current knowledge concerning the role for melatonin in human pregnancy and in the newborn. Numerous studies agree that short-term melatonin therapy is highly effective in reducing complications during pregnancy and in the neonatal period. No significant toxicity or treatment-related side effects with long-term melatonin therapy in children and adults have been reported. Treatment with melatonin might result in a wide range of health benefits, including improved quality of life and reduced healthcare costs.

  11. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  12. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Alanine aminotransferase is associated with an adverse nocturnal blood glucose profile in individuals with normal glucose regulation.

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    Jian Zhou

    Full Text Available OBJECTIVE: Although the association between alanine aminotransferase (ALT levels and risk of type 2 diabetes is well-studied, the effects of slightly increased ALT levels within the normal range on the temporal normal glucose profile remains poorly understood. METHODS: A total of 322 Chinese subjects without impaired glucose tolerance or previous diagnoses of diabetes were recruited for study from 10 hospitals in urban areas across China. All subjects wore a continuous glucose monitoring (CGM system for three consecutive days. The diurnal (06∶00-20∶00 and nocturnal (20∶00-06∶00 mean blood glucose (MBG levels were calculated. Subjects were stratified by ALT quartile level and correlation analyses were performed. RESULTS: The median ALT level was 17 IU/L, and subjects with ALT ≥17 IU/L had higher nocturnal MBG level than those with ALT 0.05. Multivariate stepwise regression analysis of elevated nocturnal MBG identified increased HOMA-IR, elevated ALT levels, and decreased homeostatic model assessment of ß-cell function as independent factors (all, P<0.05. CONCLUSIONS: Mildly elevated ALT levels, within the normal range, are associated with unfavorable nocturnal glucose profiles in Chinese subjects with normal glucose regulation.

  14. Effect of indomethacin on desmopressin resistant nocturnal polyuria and nocturnal enuresis.

    Science.gov (United States)

    Kamperis, Konstantinos; Rittig, Søren; Bower, Wendy F; Djurhuus, Jens C

    2012-11-01

    We evaluated the acute effect of indomethacin on renal water and solute handling in children with coexisting monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria, and in healthy controls. A total of 23 subjects were recruited, consisting of 12 children with monosymptomatic nocturnal enuresis and nocturnal polyuria with partial or no response to desmopressin, and 11 age matched controls. Children completed a 48-hour inpatient study protocol consisting of fractional urine collections and blood samples. Sodium and water intake were standardized. During the second night a dose of 50 mg indomethacin was administered orally before bedtime. Diuresis, urine osmolalities, clearances and fractional excretions were calculated for sodium, potassium, urea, osmoles and solute-free water. Renin, angiotensin II, aldosterone and atrial natriuretic peptide were measured in plasma. Prostaglandin E(2) was measured in urine. Indomethacin markedly decreased the nocturnal sodium, urea and osmotic excretion in children with enuresis and controls. The overall effect on nocturnal urine output was inconsistent in the group with enuresis. Subjects in whom nocturnal diuresis was decreased following administration of indomethacin remained dry. Prostaglandin inhibition leads to antidiuresis, reducing the amount of sodium, urea and osmotic excretion in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria. The sodium regulating hormones do not seem to mediate these processes. The overall effect in desmopressin nonresponders with nocturnal polyuria is variable. The extent to which indomethacin can be applied in the treatment of enuresis needs further evaluation. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2014-01-01

    Full Text Available Nitric oxide (NO deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR rats, controls treated with melatonin (0.01% in drinking water, and CR rats treated with melatonin (CR + M. The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor, decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR, and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes.

  16. Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

    International Nuclear Information System (INIS)

    Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

    2008-01-01

    Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

  17. Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

    Science.gov (United States)

    Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

    2014-10-01

    The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

  18. Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude

    NARCIS (Netherlands)

    Drijfhout, W.J; de Vries, J.B; Homan, E.J; Brons, H.F; Copinga, S; Gruppen, G; Beresford, I.J M; Hagan, R.M; Grol, Cor; Westerink, B.H.C.

    1999-01-01

    In this study we have examined the ability of melatonin and four synthetic melatonin receptor agonists to entrain endogenous melatonin secretion in rats, free running in constant darkness. The circadian melatonin profile was measured by trans-pineal microdialysis, which not only reveals the time of

  19. Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

    Science.gov (United States)

    Mao, Lulu; Dauchy, Robert T.; Blask, David E.; Slakey, Lauren M.; Xiang, Shulin; Yuan, Lin; Dauchy, Erin M.; Shan, Bin; Brainard, George C.; Hanifin, John P.; Duplessis, Tamika T.; Hill, Steven M.

    2012-01-01

    Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients. PMID:23002080

  20. Melatonin and female reproduction.

    Science.gov (United States)

    Tamura, Hiroshi; Takasaki, Akihisa; Taketani, Toshiaki; Tanabe, Manabu; Lee, Lifa; Tamura, Isao; Maekawa, Ryo; Aasada, Hiromi; Yamagata, Yoshiaki; Sugino, Norihiro

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti-aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane-bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non-receptor-mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  1. Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

    2001-01-01

    Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the

  2. Melatonin modulation of presynaptic nicotinic acetylcholine receptors located on short noradrenergic neurons of the rat vas deferens: a pharmacological characterization

    Directory of Open Access Journals (Sweden)

    Zago W.M.

    1999-01-01

    Full Text Available Melatonin, the pineal hormone produced during the dark phase of the light-dark cycle, modulates neuronal acetylcholine receptors located presynaptically on nerve terminals of the rat vas deferens. Recently we showed the presence of high affinity nicotine-binding sites during the light phase, and low and high affinity binding sites during the dark phase. The appearance of the low affinity binding sites was due to the nocturnal melatonin surge and could be mimicked by exposure to melatonin in vitro. The aim of the present research was to identify the receptor subtypes responsible for the functional response during the light and the dark phase. The rank order of potency of agonists was dimethylphenylpiperazinium (DMPP = cytisine > nicotine > carbachol and DMPP = nicotine = cytisine > carbachol, during the light and dark phase, respectively, due to an increase in apparent affinity for nicotine. Mecamylamine similarly blocked the DMPP response during the light and the dark phase, while the response to nicotine was more efficiently blocked during the light phase. In contrast, methyllycaconitine inhibited the nicotine-induced response only at 21:00 h. Since a7 nicotinic acetylcholine receptors (nAChRs have low affinity for nicotine in binding assays, we suggest that a mixed population composed of a3ß4 - plus a7-bearing nAChR subtypes is present at night. This plasticity in receptor subtypes is probably driven by melatonin since nicotine-induced contraction in organs from animals sacrificed at 15:00 h and incubated with melatonin (100 pg/ml, 4 h is not totally blocked by mecamylamine. Thus melatonin, by acting directly on the short adrenergic neurons that innervate the rat vas deferens, induces the appearance of the low affinity binding site, probably an a7 nAChR subtype.

  3. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  4. Melatonin: Buffering the Immune System

    Science.gov (United States)

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  5. Melatonin, mitochondria, and the skin.

    Science.gov (United States)

    Slominski, Andrzej T; Zmijewski, Michal A; Semak, Igor; Kim, Tae-Kang; Janjetovic, Zorica; Slominski, Radomir M; Zmijewski, Jaroslaw W

    2017-11-01

    The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors. Moreover, they attenuate the pathological processes including carcinogenesis and other hyperproliferative/inflammatory conditions. Interestingly, mitochondria appear to be a central hub of melatonin metabolism in the skin cells. Furthermore, substantial evidence has accumulated on the protective role of the melatonin against ultraviolet radiation and the attendant mitochondrial dysfunction. Melatonin and its metabolites appear to have a modulatory impact on mitochondrion redox and bioenergetic homeostasis, as well as the anti-apoptotic effects. Of note, some metabolites exhibit even greater impact than melatonin alone. Herein, we emphasize that melatonin-mitochondria axis would control integumental functions designed to protect local and perhaps global homeostasis. Given the phylogenetic origin and primordial actions of melatonin, we propose that the melatonin-related mitochondrial functions represent an evolutionary conserved mechanism involved in cellular adaptive response to skin injury and repair.

  6. Melatonin: the dark force.

    Science.gov (United States)

    Bergstrom, W H; Hakanson, D O

    1998-01-01

    Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood. Two consistent effects are the induction of sleep and an antigonadotropic influence on reproductive structure and behavior. The former is demonstrable and clinically useful in human subjects; the latter has been shown in birds, rodents, and sheep. Alteration of skin color by the contraction of melanophores was effected by pineal extracts before the discovery of melatonin. This phenomenon, seen in reptiles, amphibians, and fish, has received little recent attention. Areas of greater interest and potential importance include the antimitotic effects of melatonin on some types of tumor cells in culture and the apparent in vivo protection of immunocompetent lymphocytes during chronic stress, which reduces the functional capacity of lymphocytes in control rodents. Clinical application of the antimitotic and immunosupportive properties of melatonin seems likely in the near future. Unfortunately, this innocent molecule has been touted in two recent books and many advertisements as an aphrodisiac, rejuvenator, protector against disease, and general wonder-worker. Because interest in melatonin is high, all physicians can expect questions and may have use for the information provided in this review.

  7. The role of melatonin in radiation induced biochemical disturbances in brain and thyroid gland in adult male albino rats

    International Nuclear Information System (INIS)

    Abdel Kader, S.M.; EI-Sherbiny, E.M.

    2007-01-01

    Radiation induced changes in adult male albino male rats before and after melatonin administration were monitored to detect some biochemical changes in brain and thyroid gland. The parameters monitored were dopamine (DA), norepinephdne (NE) and gamma aminobutyric acid (GABA) in brain and triiodothyronine (T 3 ) thyroxine (T 4 ) and thyroid stimulating hormone (TSH) in serum of irradiated adult male albino rats before and after intraperitoneal injection of melatonin. Results indicated that 6.0 Gy whole body γ-irradiated rats showed gradual and significant decrease in DA, NE and GABA contents in different brain areas under investigation (cerebellum, pons+medulla oblongata, corpus striatum, cerebral cortex, hypothalamus, midbrain and hippocampus). The maximum effect of whole body γ-irradiation was observed after 21 days. Moreover, gradual and significant decrease in serum T 3 and T 4 levels were recorded after γ-irradiation. However, TSH level showed significant elevation throughout the experimental period. Melatonin at a dose level of 15 mg/kg b.wt. was intraperitoneally injected daily 30 minutes after 6.0 Gy whole body γ-irradiation, ameliorated DA, NE and GABA contents in different brain areas compared to those measured in irradiated rats. Moreover, melatonin gradually attenuated the effect of γ-irradiation on serum T 3 and T 4 levels to reach nearly the control level at day 21 after melatonin injection. However, melatonin ameliorated the elevated TSH level induced by γ-irradiation to reach its corresponding control value at day 21

  8. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  9. Melatonin labeled with hydrogen isotopes

    International Nuclear Information System (INIS)

    Dmitrevskaya, L.I.; Smushkevich, Yu.I.; Kurkovskaya, L.N.; Ponomarenko, N.K.; Suvorov, N.N.

    1989-01-01

    A study has been made of isotope exchange between melatonin and deuterium (D 2 O) or tritium (HTO) oxide under different conditions. The ease of isotope exchange for the indole ring hydrogens of melatonin in an acidic medium decreases over the series H 4 > H 2 H 6 >> H 7 , enabling the authors to process a route for production of melatonin labeled with hydrogen isotopes at positions 4,6, and 2 of the indole ring. A method has been suggested for producing melatonin labeled with hydrogen isotopes at position 2 by desulfurization of 2-(2,4-dinitro-phenylsulfenyl)melatonin at Ni(Re) (D)

  10. Melatonin labelled by hydrogen isotopes

    International Nuclear Information System (INIS)

    Dmitrevskaya, L.I.; Smushkevich, Yu.I.; Kurkovskaya, L.N.; Ponomarenko, N.K.; Suvorov, N.N.

    1988-01-01

    Isotope exchange of melatonin with deuterium (D 2 O) and tritium (HTO) oxides under different conditions is studied. Simplicity of isotope exchange of hydrogens of the indole ring of melatonin in the acidic medium decreases in series H 4 >H 2 >H 6 >>H 7 , that permits to suggest the way of melatonin preparation labelled by hydrogen isotopes in positions 4,6 and 2 of the indole ring. The way of melatonin preparation labelled by hydrogen isotopes in position 2 according to the reaction of desulfation 2-(2,4-dinitrophenylsulphenyl) melatonin at catalyst Ni(Re)(D) is suggested

  11. Effects of long-term light, darkness and oral administration of melatonin on serum levels of melatonin

    OpenAIRE

    Naser Farhadi; Majid Gharghani; Zahra Farhadi

    2016-01-01

    Background: Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Methods: Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to...

  12. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Science.gov (United States)

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  13. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Directory of Open Access Journals (Sweden)

    Ivan Ho Mien

    Full Text Available Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2 s(-1, intermittent red light (1 min on/off, or bright white light (2,500 lux near the onset of nocturnal melatonin secretion (n = 8 in each group. Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69, with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  14. Pharmacology and function of melatonin receptors

    International Nuclear Information System (INIS)

    Dubocovich, M.L.

    1988-01-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references

  15. Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.

    Directory of Open Access Journals (Sweden)

    Ari Shechter

    Full Text Available Women with premenstrual dysphoric disorder (PMDD experience mood deterioration and altered circadian rhythms during the luteal phase (LP of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03 worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025 increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05 decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

  16. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping of blood pressure during night time

    DEFF Research Database (Denmark)

    Hjortkær, Henrik; Jensen, Tonny; Kofoed, Klaus

    2014-01-01

    INTRODUCTION: Cardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been...

  17. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

    Directory of Open Access Journals (Sweden)

    Zhen-Wei Zou

    2018-06-01

    Full Text Available Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer. Keywords: Melatonin, Thyroid cancer, Radioresistance, p65, Reactive oxygen species

  18. Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment

    Directory of Open Access Journals (Sweden)

    Monika Adamczyk-Sowa

    2017-01-01

    Full Text Available Multiple sclerosis (MS is a disease involving oxidative stress (OS. This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS, 36 patients with RRMS receiving interferon beta-1b (250 μg every other day, and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily. The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs, advanced oxidation protein products (AOPP, and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone.

  19. Treatment of porcine donor cells and reconstructed embryos with the antioxidant melatonin enhances cloning efficiency.

    Science.gov (United States)

    Pang, Yun-Wei; An, Lei; Wang, Peng; Yu, Yong; Yin, Qiu-Dan; Wang, Xiao-Hong; Xin-Zhang; Qian-Zhang; Yang, Mei-Ling; Min-Guo; Wu, Zhong-Hong; Tian, Jian-Hui

    2013-05-01

    This study was conducted to investigate the effect of melatonin during the culture of donor cells and cloned embryos on the in vitro developmental competence and quality of cloned porcine embryos. At concentrations of 10(-6 )M or 10(-8) M, melatonin significantly enhanced the proliferation of porcine fetal fibroblasts (PFFs), and the blastocyst rate was significantly increased in the 10(-10) M melatonin-treated donor cell group. Cloned embryo development was also improved in embryo culture medium that was supplemented with 10(-9) M or 10(-12) M melatonin. When both donor cells and cloned embryos were treated with melatonin, the cleavage rate and total cell number of blastocysts were not significantly affected; however, the blastocyst rate was increased significantly (20.0% versus 11.7%). TUNEL assays showed that combined melatonin treatment reduced the rate of apoptotic nuclei (3.6% versus 6.1%). Gene expression analysis of the apoptosis-related genes BAX, BCL2L1, and p53 showed that the expression of BCL2L1 was significantly elevated 2.7-fold relative to the control group, while the expression of BAX and p53 was significantly decreased by 3.7-fold and 23.2-fold, respectively. In addition, we detected the expression of two melatonin receptors (MT1 and MT2) in PFFs but not in porcine cloned embryos. We conclude that exogenous melatonin enhances the development of porcine cloned embryos and improves embryo quality by inhibiting p53-mediated apoptotic pathway. The proliferation of PFFs may be mediated by receptor binding, but the beneficial effects of melatonin on embryonic development may be receptor-independent, possibly through melatonin's ability to directly scavenge free radicals. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  20. Effects of Melatonin on Early Pregnancy in Mouse: Involving the Regulation of StAR, Cyp11a1, and Ihh Expression.

    Science.gov (United States)

    Guan, Shengyu; Xie, Lu; Ma, Teng; Lv, Dongying; Jing, Wang; Tian, Xiuzhi; Song, Yukun; Liu, Zhiping; Xiao, Xianghong; Liu, Guoshi

    2017-07-27

    To test whether melatonin plays an important role in the process of early pregnancy, melatonin was given in drinking water to pregnant mice at different gestation stages. These included mice who were given melatonin 14 days prior to their successful mating (confirmed by vaginal plug) (Group A), after successful mating (Group B), and 14 days prior to and until after successful mating (Group C). Melatonin administration significantly enhanced serum as well as ovarian melatonin levels in the mice. It was observed that melatonin did not affect the natural estrous of mice. On day 0.5 of gestation (D0.5), melatonin not only elevated progesterone (P) secretion, but also upregulated expressions of StAR and Cyp11a1 , the two marker genes of corpus luteum in ovaries ( p Ihh expression in endometrium of D7.5 gestation. Melatonin treatment after successful mating improved the progesterone (P) secretion at D7.5 of gestation ( p Ihh expression in uterine endometrium. The mechanisms of melatonin to improve embryo implantation related to their actions on promoting the development of corpus luteum before gestation and helping to specify uterine receptivity in early pregnant mice.

  1. The early response of pineal N-acetyltransferase activity, melatonin and catecholamine levels in rats irradiated with gamma rays

    International Nuclear Information System (INIS)

    Kassayova, M.; Ahlersova, E.; Ahlers, I.; Pastorova, B.

    1995-01-01

    Male Wistar rats adapted to an artificial light-dark regimen were whole-body gamma-irradiated with a dose of 14.35 Gy. Irradiation, sham-irradiation and decapitation 30, 60 and 120 min after the exposure were performed between 2000 h and 0100 h in the darkness. The serotonin N-acetyltransferase activity (NAT), the concentration of melatonin and corticosterone were also determined. Ionizing radiation did not change the activity of NAT, the key enzyme of melatonin synthesis; however, it decreased the concentration of pineal melatonin. The concentration of pineal dopamine and norepinephrine decreased 30 and 120 min after exposure, while the concentration of epinephrine was elevated 30 min after irradiation, though later it was markedly decreased. The serum melatonin level was not changed but an increase in corticosterone level was observed. In the early period after exposure a decrease in pineal melatonin occurred, accompanied by a decrease in pineal catecholamines. On the contrary, in the phase of developed radiation injury the signs of increased melatonin synthesis were observed on days 3 and 4 after the exposure. (author) 6 figs., 25 refs

  2. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Lone Baandrup

    2016-10-01

    Full Text Available Abstract Background Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters. Method Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test. Results A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance. Conclusion Our data suggest melatonin as an aid during benzodiazepine withdrawal for

  3. The Safety of Melatonin in Humans

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Gögenür, Ismayil; Rosenberg, Jacob

    2016-01-01

    Exogenous melatonin has been investigated as treatment for a number of medical and surgical diseases, demonstrating encouraging results. The aim of this review was to present and evaluate the literature concerning the possible adverse effects and safety of exogenous melatonin in humans. Furthermore...... been reported. No studies have indicated that exogenous melatonin should induce any serious adverse effects. Similarly, randomized clinical studies indicate that long-term melatonin treatment causes only mild adverse effects comparable to placebo. Long-term safety of melatonin in children...

  4. Melatonin-Based Therapeutics for Neuroprotection in Stroke

    Directory of Open Access Journals (Sweden)

    Cesar V. Borlongan

    2013-04-01

    Full Text Available The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

  5. Nutritional Status in Nocturnal Hemodialysis Patients : A Systematic Review with Meta-Analysis

    NARCIS (Netherlands)

    Ipema, Karin J. R.; Struijk, Simone; van der Velden, Annet; Westerhuis, Ralf; van der Schans, Cees P.; Gaillard, Carlo A. J. M.; Krijnen, Wim P.; Franssen, Casper F. M.

    2016-01-01

    Background Hemodialysis patients experience an elevated risk of malnutrition associated with increased morbidity and mortality. Nocturnal hemodialysis (NHD) results in more effective removal of waste products and fluids. Therefore, diet and fluid restrictions are less restricted in NHD patients.

  6. Identification of melatonin in Trichoderma spp. and detection of melatonin content under controlled-stress growth conditions from T. asperellum.

    Science.gov (United States)

    Liu, Tong; Zhao, Fengzhou; Liu, Zhen; Zuo, Yuhu; Hou, Jumei; Wang, Yanjie

    2016-07-01

    T. koningii, T. harzianum, T. asperellum, T. longibrachiatum, and T. viride were analyzed using liquid chromatography-tandem mass spectrometry to determine whether melatonin is present. Results showed that there were abundant amounts of endogenous melatonin in five Trichoderma species, but no melatonin was found in any of the culture filtrates. T. asperellum had the highest amount of melatonin (27.588 ± 0.326 μg g(-1) dry mass), followed by T. koningii, T. harzianum, T. longibrachiatum, and T. viride. The endogenous melatonin content of T. asperellum in controlled-stress growth conditions was also detected. The data showed that chemical stressors (CdCl2 , CuSO4 , and H2 O2 ) provoked an increase in endogenous melatonin levels. CdCl2 had the highest stimulatory effect on melatonin production, as the product reached reaching up to three times the melatonin content of the control. NaCl stimulated a decrease of melatonin. Acidic conditions (pH 3 and pH 5) as well as slightly alkaline conditions (pH 9) resulted in an increase in the melatonin content, whereas pH11 resulted in a significant decrease in the melatonin content, only 12.276 ± 0.205 μg g(-1) dry mass. The current study is first to report melatonin content and the change of melatonin content under different stress situations in Trichoderma spp. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Development of a melatonin RIA and observation on the plasma melatonin contents in rat models of chronic hyperirritable-depression

    International Nuclear Information System (INIS)

    Rong Yang; Sun Acheng; Ma Cong; Zhao Zhong; Gui Yuning; Li Jianjun; Wang Guangkai; Guo Xiazhen

    2005-01-01

    Objective: To establish a new melatonin assay and to investigate the changes of plasma melatonin content in rat models of chronic hyperirritable-depression. Methods: Quality melatonin antiserum was obtained from immunization of Newzealand white rabbit with melatonin immunogen derived from conjugation of melatonin to bovine thyroglobulin using formaldehyde. Radioiodinated melatonin was used as tracer and a melatonin assay was developed through non-equilibrium competition. Twenty rat models of chronic hyperirritable-depression were prepared with multiple randomly-combined stimuli as previously reported. Plasma and pineal body tissue contents of melatonin in the models were examined in midsummer (n=10) and mid-winter (n=10) with the newly developed melatonin RIA. Contents of melatonin were also determined in 20 control rats. Results: The antiserum possessed very low cross-reaction rate with several melatonin analogous tested (0.09%-2.3%). At the titer of 1:1800, the maximal combination rate was 41%. The affinity constant was 1.7 x 10 9 L/M. The specific radioactivity of the tracer 125 I-melatonin was 55 μCi/μg, with radio-chemical purity of 93% and the tracer was stable at 4 degree C for 65 days. The assay was of high sensitivity (lower detection limit 5pg/ml), intra-CV, 6.5 %; inter-CV, 11%. The plasma and pineal body tissue contents of melatonin in the rat models were consistently significantly lower than those in control rats both during summer and winter, while the contents of melatonin during winter were always significantly higher than those during summer in both groups of animals. Conclusion: The newly developed assay was of good specificity and sensitivity with stable agents (65 days). The experimental results demonstrated definite correlationship between the depression disorder and melatonin contents in the rat models, however, the disorder was not seasonally affective. The seasonal variation of the melatonin contents in the animals was due to different

  8. Melatonin in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Jian-Zhi Wang

    2013-07-01

    Full Text Available Alzheimer’s disease (AD, an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP of aggregated β-amyloid (Aβ and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.

  9. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

  10. Melatonin, mitochondria and hypertension.

    Science.gov (United States)

    Baltatu, Ovidiu C; Amaral, Fernanda G; Campos, Luciana A; Cipolla-Neto, Jose

    2017-11-01

    Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin-angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin-angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

  11. Placental melatonin production and melatonin receptor expression are altered in preeclampsia: new insights into the role of this hormone in pregnancy.

    Science.gov (United States)

    Lanoix, Dave; Guérin, Pascale; Vaillancourt, Cathy

    2012-11-01

    The melatonin system in preeclamptic pregnancies has been largely overlooked, especially in the placenta. We have previously documented melatonin production and expression of its receptors in normal human placentas. In addition, we and others have shown a beneficial role of melatonin in placental and fetal functions. In line with this, decreased maternal blood levels of melatonin are found in preeclamptic compared with normotensive pregnancies. However, melatonin production and expression of its receptors in preeclamptic compared with normotensive pregnancy placentas has never been examined. This study compares (i) melatonin-synthesizing enzyme expression and activity, (ii) melatonin and serotonin, melatonin's immediate precursor, levels and (iii) expression of MT1 and MT2 melatonin receptors in placentas from preeclamptic and normotensive pregnancies. Protein and mRNA expression of aralkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), the melatonin-synthesizing enzymes, as well as MT1 and MT2 receptors were determined by RT-qPCR and Western blot, respectively. The activities of melatonin-synthesizing enzymes were assessed by radiometric assays while melatonin levels were determined by LC-MS/MS. There is a significant inhibition of AANAT, melatonin's rate-limiting enzyme, expression and activity in preeclamptic placentas, correlating with decreased melatonin levels. Likewise, MT1 and MT2 expression is significantly reduced in preeclamptic compared with normotensive pregnancy placentas. We propose that reduced maternal plasma melatonin levels may be an early diagnostic tool to identify pregnancies complicated by preeclampsia. This study indicates a clinical utility of melatonin as a potential treatment for preeclampsia in women where reduced maternal plasma levels have been identified. © 2012 John Wiley & Sons A/S.

  12. Melatonin in antinociception: its therapeutic applications.

    Science.gov (United States)

    Srinivasan, Venkatramanujam; Lauterbach, Edward C; Ho, Khek Yu; Acuña-Castroviejo, Dario; Zakaria, Rahimah; Brzezinski, Amnon

    2012-06-01

    The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord and supraspinal levels. The mechanism of antinociceptive actions of melatonin involves opioid, benzodiazepine, α(1)- and α(2)-adrenergic, serotonergic and cholinergic receptors. Most importantly however, the involvement of MT(1)/MT(2) melatonergic receptors in the spinal cord has been well documented as an antinociceptive mechanism in a number of animal models of pain perception. Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT(1)/MT(2) melatonin receptors, plays an important role in the pathophysiological mechanism of pain.

  13. Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children.

    Science.gov (United States)

    Chahbouni, Mariam; López, María Del Señor; Molina-Carballo, Antonio; de Haro, Tomás; Muñoz-Hoyos, Antonio; Fernández-Ortiz, Marisol; Guerra-Librero, Ana; Acuña-Castroviejo, Darío

    2017-10-14

    Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8-10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process.

  14. Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

    Science.gov (United States)

    Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

    2016-12-01

    Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

  15. Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions

    Directory of Open Access Journals (Sweden)

    Dun-Xian Tan

    2014-09-01

    Full Text Available Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host’s system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT, indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.

  16. Influence of age and splanchnic nerve on the action of melatonin in the adrenomedullary catecholamine content and blood glucose level in the avian group.

    Science.gov (United States)

    Mahata, S K; Mandal, A; Ghosh, A

    1988-01-01

    A single intraperitoneal (IP) melatonin injection (0.5 mg/100 g body wt.) caused an increase in norepinephrine (NE) fluorescence and elevation of NE content in newly-hatched pigeons (Columba livia), but a reduction of NE fluorescence and depletion of NE content in the adrenal medulla of newly-hatched crows (Corvus splendens) after 0.5 h of treatment. In contrast, in adults melatonin caused increase in NE fluorescence and elevation of NE content only in the parakeet (Psittacula krameri). Half an hour of IP melatonin treatment (0.5 mg/100 g body wt.) induced release of epinephrine (E) from the adrenal medulla of newly-hatched pigeon and parakeet. In contrast, in the adults melatonin caused more than a two-fold increase in E in the pigeon, and a significant increase in the crow. Single IP melatonin injection (0.5 mg/100 g body wt.) caused hypoglycemia in the newly-hatched parakeet and adult pigeon, and hyperglycemia in newly-hatched pigeon after 0.5 h of treatment. Melatonin failed to regulate glucose homoeostasis in newly-hatched and adult crow. Splanchnic denervation of the left adrenal gland was performed in the adult pigeon. The right adrenal served as the innervated gland. Melatonin-induced modulation of catecholamines following a single IP injection (0.5 mg/100 g body wt.) revealed significant increases in NE fluorescence and NE content at 4 and 12 h after treatment in the denervated gland only, which gradually approached normal levels 9 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Melatonin and pregnancy in the human.

    Science.gov (United States)

    Tamura, Hiroshi; Nakamura, Yasuhiko; Terron, M Pilar; Flores, Luis J; Manchester, Lucien C; Tan, Dun-Xian; Sugino, Norihiro; Reiter, Russel J

    2008-04-01

    The purpose of this systematic review is to access the current state of knowledge concerning the role for melatonin in human pregnancy. Melatonin is a neuroendocrine hormone secreted nightly by pineal gland and regulates biological rhythms. The nighttime serum concentration of melatonin shows an incremental change toward the end of pregnancy. This small lipophilic indoleamine crosses the placenta freely without being altered. Maternal melatonin enters the fetal circulation with ease providing photoperiodic information to the fetus. Melatonin works in a variety of ways as a circadian rhythm modulator, endocrine modulator, immunomodulator, direct free radical scavenger and indirect antioxidant and cytoprotective agent in human pregnancy, and it appears to be essential for successful pregnancy. It also seems to be involved in correcting the pathophysiology of complications during pregnancy including those due to abortion, pre-eclampsia and fetal brain damage. The scientific evidence supporting a role for melatonin in human pregnancy is summarized.

  18. Melatonin prevents possible radiotherapy-induced thyroid injury.

    Science.gov (United States)

    Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Eryılmaz, Mehmet Akif; Aktan, Meryem; Alan, Mehmet Akif; Fındık, Sıdıka; Kılınç, İbrahim

    2017-12-01

    We aimed to investigate the protective effect of melatonin in radiotherapy-induced thyroid gland injury in an experimental rat model. Thirty-two rats were divided into four groups: the control group, melatonin treatment group, radiotherapy group and melatonin plus radiotherapy group. The neck region of each rat was defined by simulation and radiated with 2 Gray (Gy) per min with 6-MV photon beams, for a total dose of 18 Gy. Melatonin was administered at a dose of 50 mg/kg through intraperitoneal injection, 15 min prior to radiation exposure. Thirty days after the beginning of the study, rats were decapitated and analyses of blood and thyroid tissue were performed. Tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels in the radiotherapy group were significantly higher than those in the melatonin plus radiotherapy group (p melatonin plus radiotherapy group (p melatonin plus radiotherapy group (p Melatonin helped protect thyroid gland structure against the undesired cytotoxic effects of radiotherapy in rats.

  19. Role of melatonin in embryo fetal development.

    Science.gov (United States)

    Voiculescu, S E; Zygouropoulos, N; Zahiu, C D; Zagrean, A M

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy beginning with the oocyte quality and finishing with the parturition. Its pregnancy night-time concentrations increase after 24 weeks of gestation, with significantly high levels after 32 weeks. Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies. In addition, chronodisruption leads to a reproductive dysfunction. Thus, the influence of melatonin on the developing human fetus may not be limited to the entertaining of circadian rhythmicity, but further studies are needed.

  20. Melatonin receptors: Current status, facts, and hypothesis

    International Nuclear Information System (INIS)

    Stankov, B.; Reiter, R.J.

    1990-01-01

    Great progress has been made in the identification of melatonin binding sites, commonly identified as melatonin receptors by many authors, in recent years. The bulk of these studies have investigated the sites using either autoradiographic and biochemical techniques with the majority of the experiments being done on the rat, Djungarian and Syrian hamster, and sheep, although human tissue has also been employed. Many of the studies have identified melatonin binding in the central nervous system with either tritium- or iodine-labelled ligands. The latter ligand seems to provide the most reproducible and consistent data. Of the central neural tissues examined, the suprachiasmatic nuclei are most frequently mentioned as a location for melatonin binding sites although binding seems to be widespread in the brain. The other tissue that has been prominently mentioned as a site for melatonin binding is the pars tuberalis of the anterior pituitary gland. There may be time-dependent variations in melatonin binding densities in both neural and pituitary gland tissue. Very few attempts have been made to identify melatonin binding outside of the central nervous system despite the widespread actions of melatonin. Preliminary experiments have been carried out on the intracellular second messengers which mediate the actions of melatonin

  1. Effects of a Heat Wave on Nocturnal Stomatal Conductance in Eucalyptus camaldulensis

    Directory of Open Access Journals (Sweden)

    Víctor Resco de Dios

    2018-06-01

    Full Text Available Nocturnal transpiration constitutes a significant yet poorly understood component of the global water cycle. Modeling nocturnal transpiration has been complicated by recent findings showing that stomata respond differently to environmental drivers over day- vs. night-time periods. Here, we propose that nocturnal stomatal conductance depends on antecedent daytime conditions. We tested this hypothesis across six genotypes of Eucalyptus camaldulensis Dehnh. growing under different CO2 concentrations (ambient vs. elevated and exposed to contrasting temperatures (ambient vs. heat wave for four days prior to the night of measurements, when all plants experienced ambient temperature conditions. We observed significant effects after the heat wave that led to 36% reductions in nocturnal stomatal conductance. The response was partly driven by changes in daytime stomatal behavior but additional factors may have come into play. We also observed significant differences in response to the heat wave across genotypes, likely driven by local adaptation to their climate of origin, but CO2 played no effect. Stomatal models may need to incorporate the role of antecedent effects to improve projections particularly after drastic changes in the environment such as heat waves.

  2. Antepartum depression severity is increased during seasonally longer nights: relationship to melatonin and cortisol timing and quantity.

    Science.gov (United States)

    Meliska, Charles J; Martínez, Luis F; López, Ana M; Sorenson, Diane L; Nowakowski, Sara; Kripke, Daniel F; Elliott, Jeffrey; Parry, Barbara L

    2013-11-01

    Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than

  3. Melatonin as Protection Against Radiation Injury

    DEFF Research Database (Denmark)

    Zetner, D.; Andersen, L. P H; Rosenberg, J.

    2016-01-01

    Introduction: Radiation is widely used in the treatment of various cancers and in radiological imaging procedures. Ionizing radiation causes adverse effects, leading to decreased quality of life in patients, by releasing free radicals that cause oxidative stress and tissue damage. The sleep......-hormone melatonin is a free radical scavenger, and induces several anti-oxidative enzymes. This review investigates the scientific literature on the protective effects of melatonin against exposure to ionizing radiation, and discusses the clinical potential of melatonin as prophylactic treatment against ionizing...... and protected against radiation enteritis. These protective effects were only documented when melatonin was administered prior to exposure to ionizing radiation. Discussion: This review documents that melatonin effectively protects animals against injury to healthy tissues from ionizing radiation. However...

  4. Pharmacokinetics of Alternative Administration Routes of Melatonin

    DEFF Research Database (Denmark)

    Zetner, D.; Andersen, L. P.H.; Rosenberg, J.

    2016-01-01

    Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. Methods: A systematic literature search was performed...... and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. Results: 10 studies were included in the review. Intranasal....... Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. Conclusion: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow...

  5. Alcoholic fermentation induces melatonin synthesis in orange juice.

    Science.gov (United States)

    Fernández-Pachón, M S; Medina, S; Herrero-Martín, G; Cerrillo, I; Berná, G; Escudero-López, B; Ferreres, F; Martín, F; García-Parrilla, M C; Gil-Izquierdo, A

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions. Its level decreases with age, and the intake of foods rich in melatonin has been considered an exogenous source of this important agent. Orange is a natural source of melatonin. Melatonin synthesis occurs during alcoholic fermentation of grapes, malt and pomegranate. The amino acid tryptophan is the precursor of all 5-methoxytryptamines. Indeed, melatonin appears in a shorter time in wines when tryptophan is added before fermentation. The aim of the study was to measure melatonin content during alcoholic fermentation of orange juice and to evaluate the role of the precursor tryptophan. Identification and quantification of melatonin during the alcoholic fermentation of orange juice was carried out by UHPLC-QqQ-MS/MS. Melatonin significantly increased throughout fermentation from day 0 (3.15 ng/mL) until day 15 (21.80 ng/mL) reaching larger amounts with respect to other foods. Melatonin isomer was also analysed, but its content remained stable ranging from 11.59 to 14.18 ng/mL. The enhancement of melatonin occurred mainly in the soluble fraction. Tryptophan levels significantly dropped from 13.80 mg/L (day 0) up to 3.19 mg/L (day 15) during fermentation. Melatonin was inversely and significantly correlated with tryptophan (r = 0.907). Therefore, the enhancement in melatonin could be due to both the occurrence of tryptophan and the new synthesis by yeast. In summary, the enhancement of melatonin in novel fermented orange beverage would improve the health benefits of orange juice by increasing this bioactive compound. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

    Science.gov (United States)

    Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

    2010-01-01

    Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

  7. Study of protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits

    International Nuclear Information System (INIS)

    Aslam, J.; Khan, W.; Bakhtiar, S.

    2017-01-01

    To evaluate the protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Pharmacology and Therapeutics in collaboration with Clinico Pathologic Laboratory, Army Medical College, Rawalpindi, from Apr to Jun 2015. Material and Methods: Eighteen rabbits were divided into three groups, each consisting of six rabbits. Baseline serum urea, creatinine, sodium and potassium were measured. Rabbits were weighed for dose calculation. A single dose of cisplatin 10mg/kg was given as I/P injection to the toxic group. The protective group received 5 mg/kg I/P melatonin for three days. Rabbits were sacrificed 72 hours after the cisplatin dose and both kidneys were sent for histopathology. Statistical analysis was carried out by using Microsoft Office Excel 2010 and SPSS version 21. Student's t-test and one way ANOVA, followed by 'Post Hoc Tukey' test was used for biochemical parameters, while Chi Square' test was used for histopathological comparison. Results: Moderate nephrotoxicity (grade-II) was seen in the toxic group, with substantial elevations of serum urea and creatinine (p<0.001), and serum sodium and potassium (p<0.01). Melatonin ameliorated the renal injury. Conclusion: The protective effects of melatonin on cisplatin-induced nephrotoxicity were due to its antioxidant properties. (author)

  8. Effects of Melatonin and Bright Light Treatment in Childhood Chronic Sleep Onset Insomnia With Late Melatonin Onset: A Randomized Controlled Study.

    Science.gov (United States)

    van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G; van der Heijden, Kristiaan B; Oort, Frans J

    2017-02-01

    Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset. Eighty-four children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N = 26), light (N = 30), or placebo pills (N = 28) for 3 to 4 weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analyzed with linear mixed model analyses. Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found. We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  9. Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men.

    Directory of Open Access Journals (Sweden)

    Simone Mäntele

    Full Text Available Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM. We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO, nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01 and lean controls (p<0.05. Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001 effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual's 24-hour mean, plasma leptin showed significant (p<0.001 diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05 of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither

  10. Participation of MT3 melatonin receptors in the synergistic effect of melatonin on cytotoxic and apoptotic actions evoked by chemotherapeutics.

    Science.gov (United States)

    Pariente, Roberto; Bejarano, Ignacio; Espino, Javier; Rodríguez, Ana B; Pariente, José A

    2017-11-01

    Melatonin has antitumor activity via several mechanisms including its antiproliferative and proapoptotic effects in addition to its potent antioxidant actions. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was performed to study the role of melatonin receptors on the cytotoxicity and apoptosis induced by the chemotherapeutic agents cisplatin and 5-fluorouracil in two tumor cell lines, such as human colorectal cancer HT-29 cells and cervical cancer HeLa cells. We found that both melatonin and the two chemotherapeutic agents tested induced a decrease in HT-29 and HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of chemotherapeutic agents, particularly, in 5-fluorouracil-challenged cells. Stimulation of cells with either of the two chemotherapeutic agents in the presence of melatonin further increased caspase-3 activation. Concomitant treatments with melatonin and chemotherapeutic agents augmented the population of apoptotic cells compared to the treatments with chemotherapeutics alone. Blockade of MT1 and/or MT2 receptors with luzindole or 4-P-PDOT was unable to reverse the enhancing effects of melatonin on both cytotoxicity, caspase-3 activation and the amount of apoptotic cells evoked by the chemotherapeutic agents, whereas when MT3 receptors were blocked with prazosin, the synergistic effect of melatonin with chemotherapy on cytotoxicity and apoptosis was reversed. Our findings provided evidence that in vitro melatonin strongly enhances chemotherapeutic-induced cytotoxicity and apoptosis in two tumor cell lines, namely HT-29 and HeLa cells and, this potentiating effect of melatonin is mediated by MT3 receptor stimulation.

  11. Melatonin: a chemical photoperiodic signal with clinical significance in humans.

    Science.gov (United States)

    Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

    1998-03-01

    Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

  12. Current management of nocturnal enuresis.

    Science.gov (United States)

    Robson, Wm Lane M

    2008-07-01

    Nocturnal enuresis is an especially common problem with the potential to have an appreciable negative impact on the emotional health of a child. Our understanding of the pathogenesis continues to improve. A disorder of sleep arousal, a low nocturnal bladder capacity, and nocturnal polyuria are the three factors that interrelate to cause nocturnal enuresis. Constipation is a very common and often unrecognized factor that appreciably affects bladder function. Successful treatment involves interventions that simultaneously improve these factors. Self-esteem improves with any form of therapy and dryness is possible for the majority of children.

  13. Melatonin Secretion Pattern in Critically Ill Patients

    DEFF Research Database (Denmark)

    Boyko, Yuliya; Holst, René; Jennum, Poul

    2017-01-01

    effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin...... secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation.......Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin...

  14. Mobile Disdrometer Observations of Nocturnal Mesoscale Convective Systems During PECAN

    Science.gov (United States)

    Bodine, D. J.; Rasmussen, K. L.

    2015-12-01

    Understanding microphysical processes in nocturnal mesoscale convective systems (MCSs) is an important objective of the Plains Elevated Convection At Night (PECAN) experiment, which occurred from 1 June - 15 July 2015 in the central Great Plains region of the United States. Observations of MCSs were collected using a large array of mobile and fixed instrumentation, including ground-based radars, soundings, PECAN Integrated Sounding Arrays (PISAs), and aircraft. In addition to these observations, three mobile Parsivel disdrometers were deployed to obtain drop-size distribution (DSD) measurements to further explore microphysical processes in convective and stratiform regions of nocturnal MCSs. Disdrometers were deployed within close range of a multiple frequency network of mobile and fixed dual-polarization radars (5 - 30 km range), and near mobile sounding units and PISAs. Using mobile disdrometer and multiple-wavelength, dual-polarization radar data, microphysical properties of convective and stratiform regions of MCSs are investigated. The analysis will also examine coordinated Range-Height Indicator (RHI) scans over the disdrometers to elucidate vertical DSD structure. Analysis of dense observations obtained during PECAN in combination with mobile disdrometer DSD measurements contributes to a greater understanding of the structural characteristics and evolution of nocturnal MCSs.

  15. [Melatonin, synthetic analogs, and the sleep/wake rhythm].

    Science.gov (United States)

    Escames, G; Acuña-Castroviejo, D

    Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm. The suprachiasmatic nuclei are the anatomical seat of the biological clock, represented by the clock genes, which code for the period and frequency of the rhythms. The photoperiod synchronizes the activity of the auprachiasmatic biological clock, which in turn induces the melatonin's rhythm. The rhythm of melatonin, peaking at 2-3 am, acts as an endogenous synchronizer that translates the environmental photoperiodic signal in chemical information for the cells. The sleep/wake cycle is a typical biological rhythm synchronized by melatonin, and the sleep/wake cycle alterations of chronobiological origin, are very sensitive to melatonin treatment. Taking advantage of the chronobiotic and antidepressive properties of melatonin, a series of synthetic analogs of this hormone, with high interest in insomnia, are now available. Melatonin is a highly effective chronobiotic in the treatment of chronobiological alterations of the sleep/wake cycle. From a pharmacokinetic point of view, the synthetic drugs derived from melatonin are interesting tools in the therapy of these alterations.

  16. The research of melatonin in hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Sun Bin; Feng Xing; Qian Zhihong; Shi Ming

    2006-01-01

    Objective: To elucidate the function of melatonin in the pathogenesis and the prognosis of hypoxic-ischemic encephalopathy (HIE) and provide the pathophysiology basis for therapying HIE with melatonin. Methods: The level of plasma melatonin of twenty normal term infants and twenty modest HIE and twenty middle-severity HIE in their acute phase and recovery phase were assayed respectively with radioimmunoassay (RIA). Then compare the difference of the melatonin level among these neonates. Results: (1) For modest HIE, the melatonin level was higher than that in the normal in the acute phase and there was no difference to the normal in the recovery phase. (2) There was no difference between the melatonin level in middle-severity HIE in the acute phase and that in the normal, but in the recovery phase it was higher than that in the normal. (3) For modest HIE, the melatonin level in acute phase was higher than that in the recovery phase, but for middle-severity HIE, it was adverse. (4) In the acute phase, the level in modest HIE was higher than that in the middle-severity HIE, but on the contrary in the recovery phase. Conclusion: Melatonin have protection action on HIE. The prognosis of modest HIE neonates with rising melatonin level in the acute phase is better than that with lower melatonin level of middle-severity HIE. (authors)

  17. Melatonin: An Underappreciated Player in Retinal Physiology and Pathophysiology

    Science.gov (United States)

    Tosini, Gianluca; Baba, Kenkichi; Hwang, Christopher K.; Iuvone, P. Michael

    2012-01-01

    In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases light-induced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential. PMID:22960156

  18. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  19. Melatonin ameliorates oxidative stress, modulates death receptor pathway proteins, and protects the rat cerebrum against bisphenol-A-induced apoptosis.

    Science.gov (United States)

    El-Missiry, Mohamed A; Othman, Azza I; Al-Abdan, Monera A; El-Sayed, Aml A

    2014-12-15

    Epidemiological reports have indicated a correlation between the increasing of bisphenol-A (BPA) levels in the environment and the incidence of neurodegenerative diseases. In the present study, the protective effect of melatonin on oxidative stress and the death receptor apoptotic proteins in the cerebrum of the bisphenol-A-treated rats were examined. Adult male rats were orally administered melatonin (10mg/kg bw) concurrently with BPA (50mg/kg bw) 3 days a week for 6 weeks. BPA exposure resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde level and the decreased glutathione level and superoxide dismutase activity in the cerebrum. BPA caused an upregulation of p53 and CD95-Fas and activation of capsases-3 and 8, resulting in cerebral cell apoptosis. Melatonin significantly attenuated the BPA-evoked brain oxidative stress, modulated apoptotic-regulating proteins and protected against apoptosis. These data suggest that melatonin modulated important steps in the death receptor apoptotic pathway which likely related to its redox control properties. Melatonin is a promising pharmacological agent for preventing the potential neurotoxicity of BPA following occupational or environmental exposures. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  1. Association between light exposure at night and nighttime blood pressure in the elderly independent of nocturnal urinary melatonin excretion.

    Science.gov (United States)

    Obayashi, Kenji; Saeki, Keigo; Iwamoto, Junko; Ikada, Yoshito; Kurumatani, Norio

    2014-07-01

    Circadian misalignment between internal and environmental rhythms dysregulates blood pressure (BP) variability because of disruption of the biological clock, resulting in increased nighttime BP. Although exposure to light-at-night is associated with the circadian misalignment, it remains unclear whether exposure to light-at-night in home settings is associated with nighttime BP. In this cross-sectional analysis of 528 elderly individuals (mean age: 72.8 years), we measured bedroom light intensity at 1-min intervals on two consecutive nights along with ambulatory BP, overnight urinary melatonin excretion and actigraphy. With regard to adjusted mean comparisons using analysis of covariance, the light-at-night group (average: ≥5 lux; n = 109) showed significantly higher nighttime systolic BP (SBP; adjusted mean: 120.8 vs. 116.5 mmHg, p = 0.01) and diastolic BP (70.1 vs. 67.1 mmHg, p light-at-night and nighttime BP in different cutoff values for light-at-night intensity (i.e. 3 and 10 lux). In conclusion, exposure to light-at-night in home settings is significantly associated with increased nighttime BP in elderly individuals independently of overnight urinary melatonin excretion. A 4.3 mmHg increase in nighttime SBP is associated with a 6.1% increase in total mortality, which corresponds to approximately 10 000 annual excess deaths in Japanese elderly population.

  2. Nocturnal continuous glucose monitoring

    DEFF Research Database (Denmark)

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...

  3. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2.

    Science.gov (United States)

    Ursing, C; Wikner, J; Brismar, K; Röjdmark, S

    2003-05-01

    Caffeine is metabolized in the liver by cytochrome P450(CYP)1A2. Recent findings imply that this enzyme may also be of importance for the metabolism of human melatonin (MT). If caffeine and MT are metabolized by the same enzyme, one may expect to find different serum MT levels after ingestion of coffee compared with placebo. Although coffee is consumed by people all over the world, few studies have focused on whether caffeine actually affects serum MT levels in normal subjects. We decided to study that particular topic. For that purpose 12 healthy individuals were tested on two occasions, one week apart. On one of these occasions they were given a capsule containing 200 mg caffeine in the evening. On the other, they received placebo. The experimental order was randomized. Serum MT levels were determined every second hour between 22:00 h and 08:00 h, and the melatonin areas under the curve (MT-AUCs) were calculated. After caffeine the serum MT level rose from 0.09 +/- 0.03 nmol/l at 22:00 h to 0.48 +/- 0.07 nmol/l at 04:00 h. The corresponding rise after placebo was less prominent (from 0.06 +/- 0.01 to 0.35 +/- 0.06 nmol/l). This was reflected by the MT-AUC which was 32% larger after ingestion of caffeine compared with placebo (MT-AUC(caffeine) 3.16 +/- 0.44 nmol/l x h vs MT-AUC(placebo) 2.39 +/- 0.40 nmol/l x h; p coffee, augments the nocturnal serum MT level, which in turn supports the notion that cytochrome P450(CYP)1A2 is involved in the hepatic metabolism of human MT.

  4. Leptin, neuropeptide Y (NPY), melatonin and zinc levels in experimental hypothyroidism and hyperthyroidism: relation with melatonin and the pineal gland.

    Science.gov (United States)

    Baltaci, Abdulkerim Kasım; Mogulkoc, Rasim

    2018-03-02

    Background Melatonin, an important neurohormone released from the pineal gland, is generally accepted to exercise an inhibitor effect on the thyroid gland. Zinc mediates the effects of many hormones and is found in the structure of numerous hormone receptors. Aim The present study aims to examine the effect of melatonin supplementation and pinealectomy on leptin, neuropeptide Y (NPY), melatonin and zinc levels in rats with hypothyroidism and hyperthyroidism. Methods This study was performed on the 70 male rats. Experimental animals in the study were grouped as follows: control (C); hypothyroidism (PTU); hypothyroidism + melatonin (PTU + M); hypothyroidism + pinealectomy (PTU + Pnx); hyperthyroidism (H); hyperthyroidism + melatonin (H + M) and hyperthyroidism + pinealectomy (H + Pnx). Blood samples collected at the end of 4-week procedures were analyzed to determine melatonin, leptin, NPY and zinc levels. Results It was found that thyroid parameters thyroid stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), total T3 (TT3) and total T4 (TT4) decreased in hypothyroidism groups and increased in the groups with hyperthyroidism. The changes in these hormones remained unaffected by melatonin supplementation and pinealectomy. Melatonin levels rose in hyperthyroidism and fell in hypothyroidism. Leptin and NPY levels increased in both hypothyroidism and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and pinealectomy, but increased in hyperthyroidism. Conclusion The results of the study demonstrate that hypothyroidism and hyperthyroidism affect leptin, NPY, melatonin and zinc values in different ways in rats. However, melatonin supplementation and pinealectomy do not have any significant influence on the changes occurring in leptin, NPY and zinc levels in thyroid dysfunction.

  5. Potency of melatonin in living beings.

    Science.gov (United States)

    Choi, Donchan

    2013-09-01

    Living beings are surrounded by various changes exhibiting periodical rhythms in environment. The environmental changes are imprinted in organisms in various pattern. The phenomena are believed to match the external signal with organisms in order to increase their survival rate. The signals are categorized into circadian, seasonal, and annual cycles. Among the cycles, the circadian rhythm is regarded as the most important factor because its periodicity is in harmony with the levels of melatonin secreted from pineal gland. Melatonin is produced by the absence of light and its presence displays darkness. Melatonin plays various roles in creatures. Therefore, this review is to introduce the diverse potential ability of melatonin in manifold aspects in living organism.

  6. Melatonin plays a protective role in postburn rodent gut pathophysiology.

    Science.gov (United States)

    Al-Ghoul, Walid M; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

    2010-05-17

    Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 micromole/kg), but not 1.86 mg/kg (8 micromole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin

  7. Melatonin for the treatment of irritable bowel syndrome.

    Science.gov (United States)

    Siah, Kewin Tien Ho; Wong, Reuben Kong Min; Ho, Khek Yu

    2014-03-14

    Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammatory reaction as well as moderation of visceral sensation. Melatonin is commonly given orally. It is categorized by the United States Food and Drug Administration as a dietary supplement. Melatonin treatment has an extremely wide margin of safety though it may cause minor adverse effects, such as headache, rash and nightmares. Melatonin was touted as a potential effective candidate for IBS treatment. Putative role of melatonin in IBS treatment include analgesic effects, regulator of gastrointestinal motility and sensation to sleep promoter. Placebo-controlled studies in melatonin suffered from heterogeneity in methodology. Most studies utilized 3 mg at bedtime as the standard dose of trial. However, all studies had consistently showed improvement in abdominal pain, some showed improvement in quality of life of IBS patients. Melatonin is a relatively safe drug that possesses potential in treating IBS. Future studies should focus on melatonin effect on gut mobility as well as its central nervous system effect to elucidate its role in IBS patients.

  8. Synthesis of 2-iodo- and 2-phenyl-[11C]melatonin: potential PET tracers for melatonin binding sites

    International Nuclear Information System (INIS)

    Chen Jiajun; Fiehn-Schulze, Brita; Firnau, Guenter; Brough, Paul A.; Snieckus, Victor

    1998-01-01

    Two 11 C-labelled melatonin derivatives, 2-iodo-[ 11 C]melatonin (2-iodo-5-methoxy-N[ 11 C-acetyl]-tryptamine, an agonist) and 2-phenyl-[ 11 C]melatonin (2-phenyl-5-methoxy-N[ 11 C-acetyl]tryptamine, a putative antagonist) were synthesized from [ 11 C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [ 11 C]carbon dioxide, (ii) conversion of the adduct to [ 11 C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [ 11 C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [ 11 C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/μmol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography

  9. Melatonin in grapes and grape-related foodstuffs: A review.

    Science.gov (United States)

    Meng, Jiang-Fei; Shi, Tian-Ci; Song, Shuo; Zhang, Zhen-Wen; Fang, Yu-Lin

    2017-09-15

    A decade has passed since melatonin was first reported in grapes in 2006. During this time, melatonin has not only been found in the berries of most wine grape (Vitis vinifera L.) cultivars, but also in most grape-related foodstuffs, e.g. wine, grape juice and grape vinegar. In this review, we discuss the melatonin content in grapes and grape-related foodstuffs (especially wine) from previous studies, the physiological function of melatonin in grapes, and the factors contributing to the production of melatonin in grapes and wines. In addition, we identify future research needed to clarify the mechanisms of grape melatonin biosynthesis and regulation, and establish more accurate analysis methods for melatonin in grapes and wines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Current role of melatonin in pediatric neurology: clinical recommendations.

    Science.gov (United States)

    Bruni, Oliviero; Alonso-Alconada, Daniel; Besag, Frank; Biran, Valerie; Braam, Wiebe; Cortese, Samuele; Moavero, Romina; Parisi, Pasquale; Smits, Marcel; Van der Heijden, Kristiaan; Curatolo, Paolo

    2015-03-01

    Melatonin, an indoleamine secreted by the pineal gland, plays a key role in regulating circadian rhythm. It has chronobiotic, antioxidant, anti-inflammatory and free radical scavenging properties. A conference in Rome in 2014 aimed to establish consensus on the roles of melatonin in children and on treatment guidelines. The best evidence for efficacy is in sleep onset insomnia and delayed sleep phase syndrome. It is most effective when administered 3-5 h before physiological dim light melatonin onset. There is no evidence that extended-release melatonin confers advantage over immediate release. Many children with developmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability have sleep disturbance and can benefit from melatonin treatment. Melatonin decreases sleep onset latency and increases total sleep time but does not decrease night awakenings. Decreased CYP 1A2 activity, genetically determined or from concomitant medication, can slow metabolism, with loss of variation in melatonin level and loss of effect. Decreasing the dose can remedy this. Animal work and limited human data suggest that melatonin does not exacerbate seizures and might decrease them. Melatonin has been used successfully in treating headache. Animal work has confirmed a neuroprotective effect of melatonin, suggesting a role in minimising neuronal damage from birth asphyxia; results from human studies are awaited. Melatonin can also be of value in the performance of sleep EEGs and as sedation for brainstem auditory evoked potential assessments. No serious adverse effects of melatonin in humans have been identified. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  11. The analgesic effects of exogenous melatonin in humans.

    Science.gov (United States)

    Andersen, Lars Peter Holst

    2016-10-01

    The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of

  12. Expression of melatonin receptors in arteries involved in thermoregulation

    International Nuclear Information System (INIS)

    Viswanathan, M.; Laitinen, J.T.; Saavedra, J.M.

    1990-01-01

    Melatonin binding sites were localized and characterized in the vasculature of the rat by using the melatonin analogue 2-[125I]iodomelatonin (125I-melatonin) and quantitative in vitro autoradiography. The expression of these sites was restricted to the caudal artery and to the arteries that form the circle of Willis at the base of the brain. The arterial 125I-melatonin binding was stable, saturable, and reversible. Saturation studies revealed that the binding represented a single class of high-affinity binding sites with a dissociation constant (Kd) of 3.4 x 10(-11) M in the anterior cerebral artery and 1.05 x 10(-10) M in the caudal artery. The binding capacities (Bmax) in these arteries were 19 and 15 fmol/mg of protein, respectively. The relative order of potency of indoles for inhibition of 125I-melatonin binding at these sites was typical of a melatonin receptor: 2-iodomelatonin greater than melatonin greater than N-acetylserotonin much much greater than 5-hydroxytryptamine. Norepinephrine-induced contraction of the caudal artery in vitro was significantly prolonged and potentiated by melatonin in a concentration-dependent manner, suggesting that these arterial binding sites are functional melatonin receptors. Neither primary steps in smooth muscle contraction (inositol phospholipid hydrolysis) nor relaxation (adenylate cyclase activation) were affected by melatonin. Melatonin, through its action on the tone of these arteries, may cause circulatory adjustments in these arteries, which are believed to be involved in thermoregulation

  13. Melatonin as a radioprotective agent: a review

    International Nuclear Information System (INIS)

    Vijayalaxmi; Reiter, Russel J.; Tan, D.-X.; Herman, Terence S.; Thomas, Charles R.

    2004-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, is well known for its functional versatility. In hundreds of investigations, melatonin has been documented as a direct free radical scavenger and an indirect antioxidant, as well as an important immunomodulatory agent. The radical scavenging ability of melatonin is believed to work via electron donation to detoxify a variety of reactive oxygen and nitrogen species, including the highly toxic hydroxyl radical. It has long been recognized that the damaging effects of ionizing radiation are brought about by both direct and indirect mechanisms. The direct action produces disruption of sensitive molecules in the cells, whereas the indirect effects (∼70%) result from its interaction with water molecules, which results in the production of highly reactive free radicals such as · OH, · H, and e aq - and their subsequent action on subcellular structures. The hydroxyl radical scavenging ability of melatonin was used as a rationale to determine its radioprotective efficiency. Indeed, the results from many in vitro and in vivo investigations have confirmed that melatonin protects mammalian cells from the toxic effects of ionizing radiation. Furthermore, several clinical reports indicate that melatonin administration, either alone or in combination with traditional radiotherapy, results in a favorable efficacy:toxicity ratio during the treatment of human cancers. This article reviews the literature from laboratory investigations that document the ability of melatonin to scavenge a variety of free radicals (including the hydroxyl radical induced by ionizing radiation) and summarizes the evidence that should be used to design larger translational research-based clinical trials using melatonin as a radioprotector and also in cancer radiotherapy. The potential use of melatonin for protecting individuals from radiation terrorism is also considered

  14. Melatonin and diabetes: from pathophysiology to the treatment perspectives

    Directory of Open Access Journals (Sweden)

    Vladimir Iosifovich Konenkov

    2013-06-01

    Full Text Available Pineal hormone melatonin synchronizes insulin secretion and glucose homeostasis with solar periods. Misalliance between melatonin-mediated circadian rhythms and insulin secretion characterizes diabetes mellitus type 1 (T1DM and type 2 (T2DM. Insulin deficiency in T1DM is accompanied by increased melatonin production. Conversely, T2DM is characterized by diminished melatonin secretion. In genome-wide association studies the variants of melatonin receptor MT2 gene (rs1387153 and rs10830963 were associated with fasting glucose, beta-cell function and T2DM. In experimental models of diabetes melatonin enhanced beta-cell proliferation and neogenesis, improved insulin resistance and alleviated oxidative stress in retina and kidneys. However, further investigation is required to assess the therapeutic value of melatonin in diabetic patients.

  15. Melatonin and diabetes: from pathophysiology to the treatment perspectives

    OpenAIRE

    V I Konenkov; V V Klimontov; S V Michurina; M A Prudnikova; I Ju Ishenko

    2013-01-01

    Pineal hormone melatonin synchronizes insulin secretion and glucose homeostasis with solar periods. Misalliance between melatonin- mediated circadian rhythms and insulin secretion characterizes diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Insulin defi- ciency in T1DM is accompanied by increased melatonin production. Conversely, T2DM is characterized by diminished melatonin secretion. In genome-wide association studies the variants of melatonin receptor MT2 gene (rs1387153 and rs10830963...

  16. Melatonin and its analogs in insomnia and depression.

    Science.gov (United States)

    Cardinali, Daniel P; Srinivasan, Venkataramanujan; Brzezinski, Amnon; Brown, Gregory M

    2012-05-01

    Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled. © 2011 John Wiley & Sons A/S.

  17. Melatonin in Antinociception: Its Therapeutic Applications

    OpenAIRE

    Srinivasan, Venkatramanujam; Lauterbach, Edward C; Ho, Khek Yu; Acuña-Castroviejo, Dario; Zakaria, Rahimah; Brzezinski, Amnon

    2012-01-01

    The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord a...

  18. Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

    Science.gov (United States)

    Roopin, Modi; Levy, Oren

    2012-01-01

    Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

  19. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

    2016-01-01

    BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were...... collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...

  20. Taxon- and Site-Specific Melatonin Catabolism

    Directory of Open Access Journals (Sweden)

    Rüdiger Hardeland

    2017-11-01

    Full Text Available Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism can be expected upon UV exposure, e.g., in plants and in the human skin. Additionally, melatonin is more strongly nonenzymatically degraded at sites of inflammation. Typical products are several hydroxylated derivatives of melatonin and N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK. Most of these products are also formed by enzymatic catalysis. Considerable taxon- and site-specific differences are observed in the main enzymatic routes of catabolism. Formation of 6-hydroxymelatonin by cytochrome P450 subforms are prevailing in vertebrates, predominantly in the liver, but also in the brain. In pineal gland and non-mammalian retina, deacetylation to 5-methoxytryptamine (5-MT plays a certain role. This pathway is quantitatively prevalent in dinoflagellates, in which 5-MT induces cyst formation and is further converted to 5-methoxyindole-3-acetic acid, an end product released to the water. In plants, the major route is catalyzed by melatonin 2-hydroxylase, whose product is tautomerized to 3-acetamidoethyl-3-hydroxy-5-methoxyindolin-2-one (AMIO, which exceeds the levels of melatonin. Formation and properties of various secondary products are discussed.

  1. Exogenous melatonin entrains rhythm and reduces amplitude of endogenous melatonin : An in vivo microdialysis study

    NARCIS (Netherlands)

    Drijfhout, W.J; Homan, E.J; Brons, H.F; Oakley, M; Skingle, M; Grol, Cor; Westerink, B.H.C.

    The circadian rhythm of melatonin production was studied using on-line, in vivo microdialysis in the rat pineal gland. With this technique it was possible to record a pronounced melatonin rhythm with very high time resolution. Three phase-markers of the rhythm were calculated from the data,

  2. Effects of electromagnetic radiation (bright light, extremely low-frequency magnetic fields, infrared radiation) on the circadian rhythm of melatonin synthesis, rectal temperature, and heart rate.

    Science.gov (United States)

    Griefahn, Barbara; Künemund, Christa; Blaszkewicz, Meinolf; Lerchl, Alexander; Degen, Gisela H

    2002-10-01

    Electromagnetic spectra reduce melatonin production and delay the nadirs of rectal temperature and heart rate. Seven healthy men (16-22 yrs) completed 4 permuted sessions. The control session consisted of a 24-hours bedrest at infrared radiation (65 degrees C) was applied from 5 pm to 1 am. Salivary melatonin level was determined hourly, rectal temperature and heart rate were continuously recorded. Melatonin synthesis was completely suppressed by light but resumed thereafter. The nadirs of rectal temperature and heart rate were delayed. The magnetic field had no effect. Infrared radiation elevated rectal temperature and heart rate. Only bright light affected the circadian rhythms of melatonin synthesis, rectal temperature, and heart rate, however, differently thus causing a dissociation, which might enhance the adverse effects of shiftwork in the long run.

  3. Effectiveness of Melatonin, as a Radiation Damage-Mitigating Drug in Modulating Liver Biochemical disorders in γ-Irradiated Rats

    International Nuclear Information System (INIS)

    El-Fatih, N.M.; Elshamy, E.

    2011-01-01

    Melatonin has an anti per oxidative effect on several tissues as well as a scavenger effect on reactive oxygen species (ROS). Whilst radiation-hazards due to free radical generation, present enormous challenges for biological and medical safety. Therefore, rats were classified into four groups; control (n= 8), (received 0.5 ml of alcoholic saline as a vehicle for 5 days). Melatonin-treated rats received 10 mg/ kg body wt, for 5 days (given to the animals in the morning via stomach tube). gamma-irradiated rats received 0.5 ml of the melatonin vehicle followed by one shot dose of 3 Gy gamma-rays. Each of these groups was compared with a further group, which-received melatonin for 5 days after 3 Gy gamma-irradiation exposure. The results revealed that all considered biochemical parameters were not changed significantly in melatonin-treated group as compared with control one. In the liver tissue of the gamma-irradiated animals (3 Gy), the oxidative stress markers malondialdehyde (MDA) and protein carbonyl (PC) were significantly increased, while a marked decrease occurred in the contents of deoxy- and ribo-nucleic acids (DNA and RNA) and glutathione (GSH) as well as activity of glutathione-S-transferase (GST). In addition, catalase (CAT) and myeloperoxidase (MPO) activities were increased. Activities of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) were significantly increased in sera of the irradiated rats. Treatment with melatonin for 5 days after gamma-rays exposure significantly modulated the radiation-induced elevations in MDA and PC levels in the liver tissue and significantly restored hepatic GSH content, GST, CAT and MPO activities. Post-irradiation treatment with melatonin showed significant higher hepatic DNA and RNA contents than irradiated rats. The activities of AST, ALP, and GGT in serum were significantly ameliorated when melatonin was administrated after irradiation. Conclusion: Melatonin has effective

  4. Clinical significance of melatonin receptors in the human myometrium.

    Science.gov (United States)

    Olcese, James; Beesley, Stephen

    2014-08-01

    To review and update the research on melatonin receptor expression in the human myometrium, in particular as it pertains to uterine contractility at labor. Summary of previous studies with the addition of new data on the transcriptional regulation of melatonin receptor expression in human myometrial cells. Not applicable. Late-term pregnant volunteers. Biopsy collection for in vitro analyses provided the original data. More recently, uterine contractions in late-term pregnant volunteers were assessed before, during, and after acute white-light exposure. Melatonin receptor signaling in myometrial cells and uterine contractions in late-term pregnant volunteers. Melatonin acts through the MTNR1B melatonin receptor that is expressed in the myometrium at late term to synergistically enhance oxytocin-dependent signaling and contractions. Acute inhibition of endogenous melatonin levels with light reversibly suppresses uterine contractions. These results point to a significant role for circulating melatonin in the timing and degree of uterine contractions in late-term pregnancy. Understanding the regulation of melatonin receptors remains a future objective. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

    Full Text Available Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1, interferon gamma (IFN-γ, programmed cell death-receptor (Fas and Tumor necrosis factor-alpha (TNF-α mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA, cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

  6. Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.

    Science.gov (United States)

    Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

    2004-09-01

    Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

  7. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2017-02-01

    Full Text Available Adult-onset chronic non-communicable diseases (NCDs can originate from early life through so-called the “developmental origins of health and disease” (DOHaD or “developmental programming”. The DOHaD concept offers the “reprogramming” strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

  8. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    Science.gov (United States)

    Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

    2017-02-16

    Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

  9. Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

    Science.gov (United States)

    Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

    2016-01-01

    Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect

  10. Local Actions of Melatonin in Somatic Cells of the Testis.

    Science.gov (United States)

    Frungieri, Mónica Beatriz; Calandra, Ricardo Saúl; Rossi, Soledad Paola

    2017-05-31

    The pineal hormone melatonin regulates testicular function through the hypothalamic-adenohypophyseal axis. In addition, direct actions of melatonin in somatic cells of the testis have been described. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular growth, proliferation, energy metabolism and the oxidation state, and consequently may regulate spermatogenesis. These data pinpoint melatonin as a key player in the regulation of testicular physiology (i.e., steroidogenesis, spermatogenesis) mostly in seasonal breeders. In patients with idiopathic infertility, melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, and provides protective effects against oxidative stress in testicular mast cells. Consequently, melatonin is also involved in the modulation of inflammatory and oxidant/anti-oxidant states in testicular pathology. Overall, the literature data indicate that melatonin has important effects on testicular function and male reproduction.

  11. Melatonin delays clutch initiation in a wild songbird

    Science.gov (United States)

    Greives, Timothy J.; Kingma, Sjouke A.; Beltrami, Giulia; Hau, Michaela

    2012-01-01

    The hormone melatonin is known to play an important role in regulating many seasonal changes in physiology, morphology and behaviour. In birds, unlike in mammals, melatonin has thus far been thought to play little role in timing seasonal reproductive processes. This view is mainly derived from laboratory experiments on male birds. This study tests whether melatonin is capable of influencing the timing of clutch initiation in wild female songbirds. Free-living female great tits (Parus major) treated with melatonin-filled implants prior to the breeding season initiated their first clutch of the season significantly later than females carrying an empty implant. Melatonin treatment did not affect clutch size. Further, melatonin treatment did not delay the onset of daily activity in the wild nor adversely affect body mass in captivity compared with controls. These data suggest a previously unknown role for this hormone in regulating the timing of clutch initiation in the wild. PMID:22171024

  12. Melatonin and mitochondrial function during ischemia/reperfusion injury.

    Science.gov (United States)

    Ma, Zhiqiang; Xin, Zhenlong; Di, Wencheng; Yan, Xiaolong; Li, Xiaofei; Reiter, Russel J; Yang, Yang

    2017-11-01

    Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin's protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.

  13. Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring - The NOCTURNE Study.

    Science.gov (United States)

    Kario, Kazuomi; Tomitani, Naoko; Kanegae, Hiroshi; Ishii, Hajime; Uchiyama, Kazuaki; Yamagiwa, Kayo; Shiraiwa, Toshihiko; Katsuya, Tomohiro; Yoshida, Tetsuro; Kanda, Kiyomi; Hasegawa, Shinji; Hoshide, Satoshi

    2017-06-23

    Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled. The ARB/CCB combination therapy (irbesartan 100 mg+amlodipine 5 mg) achieved a significantly greater reduction in nocturnal home systolic BP (primary endpoint) than the ARB/diuretic combination (daily irbesartan 100 mg+trichlormethiazide 1 mg) (-14.4 vs. -10.5 mmHg, P<0.0001), independently of urinary sodium excretion and/or nocturnal BP dipping status. However, the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity (diabetes, chronic kidney disease, and elderly patients). This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM. The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake, despite the similar impact of the 2 combinations in patients with higher salt sensitivity.

  14. Melatonin membrane receptors in peripheral tissues: Distribution and functions

    Science.gov (United States)

    Slominski, Radomir M.; Reiter, Russel J.; Schlabritz-Loutsevitch, Natalia; Ostrom, Rennolds S.; Slominski, Andrzej T.

    2012-01-01

    Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes. PMID:22245784

  15. The role of melatonin in the light of current knowledge

    Directory of Open Access Journals (Sweden)

    Barbara Algiert

    2016-02-01

    Full Text Available Recent studies have shed new light on the role of melatonin. Local tissue synthesis has been investigated. A special system responsible for the synthesis and metabolism of melatonin has developed in the human skin. The primary role of melatonin is the regulation of circadian rhythms, but studies have demonstrated the diversity of its activities. Potent antioxidant action of melatonin in the skin is emphasized. The skin has developed a specific antioxidant melatoninergic system which protects against oxidative stress. Presence of melatonin metabolites in the skin confirms its strong antioxidant properties. Melatonin has the ability to restore the physiological balance between synthesis and degradation of extracellular matrix proteins by induction of heme oxygenase in murine fibroblasts irradiated with UVR. There is a hypothesis concerning the participation of melatonin in etiology of vitiligo. Disturbances of melatonin skin synthesis and dysregulation of its receptors may explain the pathogenesis of disease.

  16. ARM Support for the Plains Elevated Convection at Night (AS-PECAN) Field Campaign Report

    Energy Technology Data Exchange (ETDEWEB)

    Turner, D. D. [National Oceanic and Atmospheric Administration (NOAA), Silver Spring, MD (United States); Geerts, B. [Univ. of Wyoming, Laramie, WY (United States)

    2016-04-01

    The Plains Elevated Convection at Night (PECAN) field campaign was a large multi-agency/multi-institutional experiment that targeted nighttime convection events in the central plains of the United States in order to better understand a range of processes that lead to the initiation and upscale growth of deep convection. Both weather and climate models struggle to properly represent the timing and intensity of precipitation in the central United States in their simulations. These models must be able to represent the interactions between the nocturnal stable boundary layer (SBL), the nocturnal low-level jet (LLJ), and a reservoir of convectively available potential energy (CAPE) that frequently exists above the SBL. Furthermore, a large fraction of the nocturnal precipitation is due to the organization of mesoscale convective systems (MCSs). In particular, there were four research foci for the PECAN campaign: •The initiation of elevated nocturnal convection focus seeks to elucidate the mesoscaleenvironmental characteristics and processes that lead to convection initiation (CI) and provide baseline data on the early evolution of mesoscale convective clusters. •The dynamics and internal structure and microphysics of nocturnal MCSs focus will investigatethe transition from surface-based to elevated storm structure, the interaction of cold pools generated by MCSs with the nocturnal stable boundary layer, and how the organization and evolution of elevated convection is influenced by the SBL and the vertical profile of wind and stability above the LLJ. •The bores and wave-like disturbances focus seeks to advance knowledge of the initiation of boredisturbances by convection, how the vertical profile of stability and winds modulate bore structure, the role of these disturbances in the initiation, maintenance, and organization of deep convection, and their impact on the LLJ and SBL. •The LLJ focus seeks to understand the processes that influence the spatial and

  17. Melatonin improves the quality of in vitro produced (IVP bovine embryos: implications for blastocyst development, cryotolerance, and modifications of relevant gene expression.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    Full Text Available To evaluate the potential effects of melatonin on the kinetics of embryo development and quality of blastocyst during the process of in vitro bovine embryo culture. Bovine cumulus-oocyte complexes (COCs were fertilized after in vitro maturation. The presumed zygotes were cultured in in vitro culture medium supplemented with or without 10(-7 M melatonin. The cleavage rate, 8-cell rate and blastocyst rate were examined to identify the kinetics of embryo development. The hatched blastocyst rate, mortality rate after thawing and the relevant transcript abundance were measured to evaluate the quality of blastocyst. The results showed that melatonin significantly promoted the cleavage rate and 8-cell embryo yield of in vitro produced bovine embryo. In addition, significantly more blastocysts were observed by Day 7 of embryo culture at the presence of melatonin. These results indicated that melatonin accelerated the development of in vitro produced bovine embryos. Following vitrification at Day 7 of embryo culture, melatonin (10(-7 M significantly increased the hatched blastocyst rate from 24 h to 72 h and decreased the mortality rate from 48 h to 72 h after thawing. The presence of melatonin during the embryo culture resulted in a significant increase in the gene expressions of DNMT3A, OCC, CDH1 and decrease in that of AQP3 after thawing. In conclusion, melatonin not only promoted blastocyst yield and accelerated in vitro bovine embryo development, but also improved the quality of blastocysts which was indexed by an elevated cryotolerance and the up-regulated expressions of developmentally important genes.

  18. Clinical uses of melatonin: evaluation of human trials.

    Science.gov (United States)

    Sánchez-Barceló, E J; Mediavilla, M D; Tan, D X; Reiter, R J

    2010-01-01

    During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses.

  19. Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

    Science.gov (United States)

    Peschke, Elmar; Bähr, Ina; Mühlbauer, Eckhard

    2013-01-01

    The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes. PMID:23535335

  20. Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

    Science.gov (United States)

    Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

    2017-06-01

    The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, poral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Melatonin ve Klinik Önemi

    OpenAIRE

    Fehmi, Özgüner; Özcankaya, Ramazan; Delibaş, Namık; Koyu, Ahmet; Çalışkan, Sadettin

    2009-01-01

    SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 1995 Aralık; 2(4) Melatonin ve Klinik Önemi Fehmi Özgüner Ramazan Özcankaya Namık Delibaş Ahmet Koyu Sadettin Çalışkan . Özet Melatonin karanlık periyotta sentezlenir ve salınır, ayrıca karanlığın süresi hakkındaki bilginin değerlendirilmesine aracılık eder. Melatonin sirkadiyan ritmi, gençlerde oldukça düzenlidir, yaşlılıkta sıklıkla siklus bozulma gösterir ve bir hipomelatoninemi sendromu ola...

  2. Topical melatonin for treatment of androgenetic alopecia.

    Science.gov (United States)

    Fischer, Tobias W; Trüeb, Ralph M; Hänggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-10-01

    In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test. FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P melatonin solution can be considered as a treatment option in androgenetic alopecia.

  3. Protective effect of melatonin on thrombocytopoiesis in irratiated mice

    International Nuclear Information System (INIS)

    Liu Aiguo; Hu Qun; Yang Mo; Li Zhiguang; Huang Weizhe; Pang Yaxuan; Li Guixia; Wu Baixiang; Huo Taihui

    2005-01-01

    Objective: To study the protective effect of melatonin on thrombocytopoiesis (T) and its mechanism in total-bodily irradiated mice. Methods: Altogether 18 female BALB/c mice were randomly divided into three experimental groups (6 each): Group 1(normal control, N) received neither irradiation nor melatonin; Group 2 (model control, C); received total body-irradiation for 4 Gy gamma-rays and Group 3 (melatonin, M), received melatonin after irradiation at the dosage of 10 mg·kg -1 ·d -1 via i. p. injection in consecutive 21 days. In Group C normal saline instead of melatonin was administered in the same way as above. Peripheral blood platelets and white blood cells (WBC) were analyzed for the three groups on day 0, day 7, day 14, and day 21. All the mice were sacrificed to collect bone marrow cells for the assays of colony-forming unit-megakaryocyte (CFU-MK) and of colony-forming unit-fibroblast (CFU-F). The effects of melatonin of different concentrations (0-500 nmol/L) on CFU-MK formation were observed in vitro. Results: The results showed that melatonin enhanced the recovery of T. Moreover, melatonin also promoted the increase of CFU-F (28 ± 10.4 vs 14.6 ± 2.8) and CFU-MK (19.63 ± 3.28 vs 11 ± 2.24) in vivo. The amount of CFU-MK in vitro was dependent on the concentration of melatonin. Compared with the control group, the size of CFU-MK in Group M was much larger and MK cells were more mature, especially when the melatonin concentration was 200 nmol/L. Conclusion: Melatonin provides protective effect on T in irradiated mice. It enhances T in vivo and promotes the growth of bone marrow stromal cells as well as megakaryocytes in vitro. Therefore, we speculate that the T-protective activity of melatonin may be mediated via promoting growth of the progenitors of platelet, megakaryocytes, and bone marrow stromal cells. (authors)

  4. Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

    Science.gov (United States)

    Watanabe, Kazushi; Hamada, Fumiaki; Wakatsuki, Akihiko; Nagai, Ryuhei; Shinohara, Koichi; Hayashi, Yoshihiro; Imamura, Rina; Fukaya, Takao

    2012-08-01

    The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.

  5. Changes in plasma melatonin levels and pineal organ melatonin synthesis following acclimation of rainbow trout (Oncorhynchus mykiss) to different water salinities.

    Science.gov (United States)

    López-Patiño, Marcos A; Rodríguez-Illamola, Arnau; Gesto, Manuel; Soengas, José L; Míguez, Jesús M

    2011-03-15

    Melatonin has been suggested to play a role in fish osmoregulation, and in salmonids has been related to the timing of adaptive mechanisms during smolting. It has been described that acclimation to different environmental salinities alters levels of circulating melatonin in a number of fish species, including rainbow trout. However, nothing is known regarding salinity effects on melatonin synthesis in the pineal organ, which is the main source of rhythmically produced and secreted melatonin in blood. In the present study we have evaluated, in rainbow trout, the effects of acclimation to different salinities on day and night plasma melatonin values and pineal organ melatonin synthesis. Groups of freshwater (FW)-adapted rainbow trout were placed in tanks with four different levels of water salinity (FW, 6, 12, 18 p.p.t.; parts per thousand) and maintained for 6 h or 5 days. Melatonin content in plasma and pineal organs, as well as the pineal content of serotonin (5-HT) and its main oxidative metabolite (5-hydroxyindole-3-acetic acid; 5-HIAA) were measured by high performance liquid chromatography. In addition, day-night changes in pineal organ arylalkylamine N-acetyltransferase (AANAT2) activity and aanat2 gene expression were studied. Plasma osmolalities were found to be higher in rainbow trout exposed to all salinity levels compared with the control FW groups. A salinity-dependent increase in melatonin content was found in both plasma and pineal organs. This effect was observed during the night, and was related to an increase in aanat2 mRNA abundance and AANAT2 enzyme activity, both of which also occurred during the day. Also, the levels of indoles (5-HT, 5-HIAA) in the pineal organ were negatively affected by increasing water salinity, which seems to be related to the higher recruitment of 5-HT as a substrate for the increased melatonin synthesis. A stimulatory effect of salinity on pineal aanat2 mRNA expression was also identified. These results indicate that

  6. Radioprotective effects of melatonin on radiation-induced cataract

    International Nuclear Information System (INIS)

    Karslioglu, Ie.; Ertekin, M.V.; Taysi, S.; Kocer, Ie.; Sezen, O.; Koc, M.; Bakan, N.; Gepdiremen, A.

    2005-01-01

    One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10 th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide

  7. Melatonin alleviates low PS I-limited carbon assimilation under elevated CO2 and enhances the cold tolerance of offspring in chlorophyll b-deficient mutant wheat

    DEFF Research Database (Denmark)

    Li, Xiangnan; Brestic, Marian; Tan, Dun-xian

    2018-01-01

    the activities of ATPase and sucrose synthesis and maintaining a relatively higher level of total chlorophyll concentration in leaves. In addition, melatonin priming in maternal plants at grain filling promoted the seed germination in offspring by accelerating the starch degradation and improved the cold...... tolerance of seedlings through activating the antioxidant enzymes and enhancing the photosynthetic electron transport efficiency. These findings suggest the important roles of melatonin in plant response to future climate change, indicating that the melatonin priming at grain filling in maternal plants...

  8. Nocturnal Polyuria: Excess of Nocturnal Urine Production, Excess of Definitions-Influence on Renal Function Profile.

    Science.gov (United States)

    Goessaert, An-Sofie; Walle, Johan Vande; Bosch, Ruud; Hoebeke, Piet; Everaert, Karel

    2016-03-01

    This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. This post hoc analysis was based on a prospective study in which participants completed a bladder diary, collected urine and provided a blood sample. With an age dependent nocturnal polyuria index greater than 20% to 33% as the referent 4 definitions of nocturnal polyuria were compared, including 1) nocturnal polyuria index greater than 33%, 2) nocturnal urine production greater than 90 ml per hour and 3) greater than 10 ml/kg, and 4) nocturia index greater than 1.5. In 112 male and female participants significant differences in baseline characteristics and bladder diary parameters were found according to definition. Diuresis rate, free water clearance and sodium clearance had similar 24-hour courses in the subgroups with and without polyuria by each definition. The range varied more in the subgroup with vs without polyuria, especially at night for diuresis rate and free water clearance. At night the latter decreased in the polyuria subgroup based on each definition (p polyuria subgroups was found only for urine production greater than 90 ml per hour and polyuria index greater than 20% to 33%. For each definition sodium clearance remained high in the polyuria subgroup, which differed significantly from the no polyuria subgroups (p polyuria by definition. The renal function profile indicating the pathophysiological mechanism of nocturnal polyuria did not seem to be influenced by definition but free water clearance and sodium clearance cutoff sensitivity differed substantially. These results must be confirmed in a larger homogeneous sample. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  10. Role of melatonin in embryo fetal development

    OpenAIRE

    Voiculescu, SE; Zygouropoulos, N; Zahiu, CD; Zagrean, AM

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal mela...

  11. Afternoon serum-melatonin in sleep disordered breathing.

    Science.gov (United States)

    Ulfberg, J; Micic, S; Strøm, J

    1998-08-01

    To study afternoon serum-melatonin values in patients with sleep disordered breathing. Melatonin has a strong circadian rhythm with high values during the night-time and low values in the afternoon. Sleep disordered breathing may change the circadian rhythm of melatonin which may have diagnostic implications. The Sleep Laboratory, The Department of Internal Medicine, Avesta Hospital, Sweden, and the Department of Anaesthesiology, Glostrup University Hospital, Copenhagen, Denmark. We examined 60 consecutive patients admitted for sleep disordered breathing and 10 healthy non snoring controls. The patients underwent a sleep apnoea screening test having a specificity of 100% for the obstructive sleep apnoea syndrome (OSAS) using a combination of static charge sensitive bed and oximetry. Obstructive sleep apnoea syndrome was found in 49 patients, eight patients had borderline sleep disordered breathing (BSDB) and three patients were excluded due to interfering disease. Patients and controls had an afternoon determination of serum-melatonin. The Epworth Sleepiness Scale was used to score day-time sleepiness. In comparison with normal controls patients suffering from OSAS had significantly higher serum-melatonin levels in the afternoon. However, as a diagnostic test for OSAS in patients with sleep disordered breathing serum-melatonin showed a low sensitivity but a high specificity. The results indicate that breathing disorders during sleep in general affect pineal function. Sleep disordered breathing seems to disturb pineal function. Determination of afternoon serum-melatonin alone or together with a scoring of daytime sleepiness does not identify OSAS-patients in a heterogeneous population of patients complaining of heavy snoring and excessive daytime sleepiness.

  12. Melatonin mitigates neomycin-induced hair cell injury in zebrafish.

    Science.gov (United States)

    Oh, Kyoung Ho; Rah, Yoon Chan; Hwang, Kyu Ho; Lee, Seung Hoon; Kwon, Soon Young; Cha, Jae Hyung; Choi, June

    2017-10-01

    Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides. The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio). Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 μM neomycin for 1 h. Surviving hair cells within four neuromasts were compared with that of a control group. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The changes of ultrastructure were confirmed using a scanning electron microscope. Melatonin alleviated neomycin-induced hair cell injury in neuromasts (neomycin + melatonin 100 μM: 13.88 ± 0.91 cells, neomycin only: 7.85 ± 0.90 cells; n = 10, p melatonin for 1 h in SEM findings. Melatonin is effective in alleviating aminoglycoside-induced hair cell injury in zebrafish. The results of this study demonstrated that melatonin has the potential to reduce apoptosis induced by aminoglycosides in zebrafish.

  13. Nocturnal Polyuria : Excess of Nocturnal Urine Production, Excess of Definitions-Influence on Renal Function Profile

    NARCIS (Netherlands)

    Goessaert, An-Sofie; Walle, Johan Vande; Bosch, JLHR; Hoebeke, Piet; Everaert, Karel

    2016-01-01

    PURPOSE: This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. MATERIALS AND METHODS: This post hoc analysis was based on a prospective

  14. The role of melatonin as an antioxidant in the follicle

    Directory of Open Access Journals (Sweden)

    Tamura Hiroshi

    2012-01-01

    Full Text Available Abstract Melatonin (N-acetyl-5-methoxytryptamine is secreted during the dark hours at night by pineal gland, and it regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It has been believed that melatonin regulates ovarian function by the regulation of gonadotropin release in the hypothalamus-pituitary gland axis via its specific receptors. In addition to the receptor mediated action, the discovery of melatonin as a direct free radical scavenger has greatly broadened the understanding of melatonin's mechanisms which benefit reproductive physiology. Higher concentrations of melatonin have been found in human preovulatory follicular fluid compared to serum, and there is growing evidence of the direct effects of melatonin on ovarian function especially oocyte maturation and embryo development. Many scientists have focused on the direct role of melatonin on oocyte maturation and embryo development as an anti-oxidant to reduce oxidative stress induced by reactive oxygen species, which are produced during ovulation process. The beneficial effects of melatonin administration on oocyte maturation and embryo development have been confirmed by in vitro and in vivo experiments in animals. This review also discusses the first application of melatonin to the clinical treatment of infertile women and confirms that melatonin administration reduces intrafollicular oxidative damage and increase fertilization rates. This review summarizes our recent works and new findings related to the reported beneficial effects of melatonin on reproductive physiology in its role as a reducer of oxidative stress, especially on oocyte maturation and embryo development.

  15. Melatonin in perioperative medicine: Current perspective

    Directory of Open Access Journals (Sweden)

    Souvik Maitra

    2013-01-01

    Full Text Available Melatonin, a new addition to the armamentarium of anesthesiologist, has some unique properties that are highly desirable in routine peri-operative care. Available clinical data show that preoperative melatonin is as effective as benzodiazepines in reducing preoperative anxiety with minimal action on psychomotor performance and sleep wake cycle. It may be considered as a safe and effective alternative of benzodiazepines as preoperative anxiolytic. It may have opioid sparing effect, may reduce intraocular pressure, and have role in prevention of postoperative delirium. The short-term administration of melatonin is free from significant adverse effects also.

  16. Melatonin - a key to the evaluation of the effects of electric; Melatonin - Schluessel fuer die Bewertung der Wirkung elektrischer und magnetischer Felder?

    Energy Technology Data Exchange (ETDEWEB)

    Wunstorf, B.; Lichtenberg, W. [Fachhochschule Hamburg (Germany). Fachbereich Oekotrophologie; Boikat, U. [BAGS, Amt fuer Gesundheit, Hamburg (Germany)

    2000-09-01

    The human pineal gland produces melatonin in a circadian rhythm. The substance has different functions - as a hormone, as an antioxidant and as a neurotransmitter. The secretion of melatonin and its tumor inhibition function can be influenced by electric and magnetic fields. Investigations have been carried out with rodents which have a melatonin rhythm similar to humans; nevertheless, they show a high variability between the species. The present state of knowledge only allows limited use of melatonin as an indicator for the impact of electric and magnetic fields. (orig.) [German] In der Epiphyse des Menschen wird in circadianem Rhythmus Melatonin produziert und ausgeschuettet. Die Substanz hat unterschiedliche Funktionen - als Hormon, Antioxidans und Neurotransmitter. Seine Ausschuettung und seine tumorhemmende Funktion koennen durch elektrische und magnetische Felder beeinflusst werden. Anhand von Nagern, die einen dem Menschen aehnlichen Melatoninrhythmus haben, allerdings eine hohe Speziesvarianz aufweisen, wurden diese Funktionen untersucht. Nach dem jetzigen Kenntnisstand eignet sich Melatonin nur bedingt als Indikator fuer die Wirkungen elektrischer und magnetischer Felder. (orig.)

  17. A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man

    International Nuclear Information System (INIS)

    Wetterberg, L.; Friberg, Y.; Eriksson, O.; Vangbo, B.

    1978-01-01

    A simplified and rapid radioimmunoassay (RIA) for melatonin is presented. Melatonin is extracted from serum, plasma or urine and RIA is performed by using [ 3 H]melatonin as the tracers. The standard curve covers the range 0.2-4.3 nmol/l. By increasing the sample volume the range can be extended to 0.06 nmol/l. The intra-assay variability is 7% (relative standard deviation=rsd) and the inter-assay variability is 10% (rsd). The recovery of melatonin added to calf serum is 96%. The long term variability of the assay (43 assays on aliquots of one serum sample during 6 months) is 13.5% (rsd). The serum levels in man after one oral dose of 430 μmol melatonin have been measured. The peak value, 620 nmol/l, was noted after 0.5 h and the melatonin concentration was still above the normal range at 24 h (2.1 nmol/l). (Auth.)

  18. [Melatonin secretion in women of advanced reproductive age].

    Science.gov (United States)

    Ermolenko, K S; Rapoport, S I; Solov'eva, A V

    2013-01-01

    The patient's age is a key factor determining success of in vitro fertilization. The ovarian reserve and oocyte quality are known to decrease with age. Much attention has been given recently to the role of epiphysis and its hormone, melatonin, in synchronization of daily and seasonal biorhythms in anti-stress protection and neuroregulation of reproductive processes. The aim of our work was to study melatonin levels in infertile women of reproductive age. We also measured sex hormones, anti-Mullerian hormone, FSH, and LH in blood and melatonin sulfate in urine at 8 points (RIA). Women of advanced reproductive age showed markedly reduced melatonin secretion due to functional disorders in the hypothalamic-pituitary-gonadal axis. Results of the study suggest the necessity of prescription of exogenous melatonin to the patients included in assisted reproduction programs for the improvement of their efficacy.

  19. A review of sleep disorders and melatonin.

    Science.gov (United States)

    Xie, Zizhen; Chen, Fei; Li, William A; Geng, Xiaokun; Li, Changhong; Meng, Xiaomei; Feng, Yan; Liu, Wei; Yu, Fengchun

    2017-06-01

    Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short- or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.

  20. Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

    Directory of Open Access Journals (Sweden)

    Russel J. Reiter

    2013-04-01

    Full Text Available Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fertilization-embryo transfer, treating them with melatonin improves implantation and pregnancy rates. Melatonin synthesis as well as its receptors have also been identified in the placenta. In this organ, melatonin seems to be of particular importance for the maintenance of the optimal turnover of cells in the villous trophoblast via its ability to regulate apoptosis. For male gametes, melatonin has also proven useful in protecting them from oxidative damage and preserving their viability. Incubation of ejaculated animal sperm improves their motility and prolongs their viability. For human sperm as well, melatonin is also a valuable agent for protecting them from free radical damage. In general, the direct actions of melatonin on the gonads and adnexa of mammals indicate it is an important agent for maintaining optimal reproductive physiology.

  1. Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

    Science.gov (United States)

    Reiter, Russel J.; Rosales-Corral, Sergio A.; Manchester, Lucien C.; Tan, Dun-Xian

    2013-01-01

    Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fertilization-embryo transfer, treating them with melatonin improves implantation and pregnancy rates. Melatonin synthesis as well as its receptors have also been identified in the placenta. In this organ, melatonin seems to be of particular importance for the maintenance of the optimal turnover of cells in the villous trophoblast via its ability to regulate apoptosis. For male gametes, melatonin has also proven useful in protecting them from oxidative damage and preserving their viability. Incubation of ejaculated animal sperm improves their motility and prolongs their viability. For human sperm as well, melatonin is also a valuable agent for protecting them from free radical damage. In general, the direct actions of melatonin on the gonads and adnexa of mammals indicate it is an important agent for maintaining optimal reproductive physiology. PMID:23549263

  2. Maternal and placental melatonin: actions and implication for successful pregnancies.

    Science.gov (United States)

    Sagrillo-Fagundes, L; Soliman, A; Vaillancourt, C

    2014-06-01

    Melatonin is one of the main sources of mitochondrial protection and its protective effects are equal or even better if compared with several consecrated antioxidants. Furthermore, the activation of specific melatonin receptors triggers several cellular pathways that improve the oxidoreduction and inflammatory cellular state. The discovery of the melatoninergic machinery in placental cells was the first step to understand the effects of this indoleamine during pregnancy. In critical points of pregnancy, melatonin has been pointed as a protagonist and its beneficial effects have been shown as essential for the control of trophoblastic function and development. On the contrary of the plasmatic melatonin (produced in pineal gland), placental melatonin does not vary according to the circadian cycle and acts as an autocrine, paracrine, intracrine, and endocrine hormone. The important effects of melatonin in placenta have been demonstrated in the physiopathology of pre-eclampsia with alterations in the levels of melatonin and in the expression of its receptors and synthetizing enzymes. Some authors suggested melatonin as a biomarker of pre-eclampsia and as a possible treatment for this disease and other obstetric pathologies associated with placental defect and increases in oxidative stress. This review will approach the beneficial effects of melatonin on placenta homeostasis and consequently on pregnancy and fetal health.

  3. Preliminary evidence that light through the eyelids can suppress melatonin and phase shift dim light melatonin onset.

    Science.gov (United States)

    Figueiro, Mariana G; Rea, Mark S

    2012-05-07

    A previous study reported a method for measuring the spectral transmittance of individual human eyelids. A prototype light mask using narrow-band "green" light (λmax = 527 nm) was used to deliver light through closed eyelids in two within-subjects studies. The first study investigated whether an individual-specific light dose could suppress melatonin by 40% through the closed eyelid without disrupting sleep. The light doses were delivered at three times during the night: 1) beginning (while subjects were awake), 2) middle (during rapid eye movement (REM) sleep), and 3) end (during non-REM sleep). The second study investigated whether two individual-specific light doses expected to suppress melatonin by 30% and 60% and delivered through subjects' closed eyelids before the time of their predicted minimum core body temperature would phase delay the timing of their dim light melatonin onset (DLMO). Compared to a dark control night, light delivered through eyelids suppressed melatonin by 36% (p = 0.01) after 60-minute light exposure at the beginning, 45% (p = 0.01) at the middle, and 56% (p light levels 1 and 2, respectively. These studies demonstrate that individual-specific doses of light delivered through closed eyelids can suppress melatonin and phase shift DLMO and may be used to treat circadian sleep disorders.

  4. Dietary melatonin alters uterine artery hemodynamics in pregnant Holstein heifers.

    Science.gov (United States)

    Brockus, K E; Hart, C G; Gilfeather, C L; Fleming, B O; Lemley, C O

    2016-04-01

    The objective was to examine uterine artery hemodynamics and maternal serum profiles in pregnant heifers supplemented with dietary melatonin (MEL) or no supplementation (CON). In addition, melatonin receptor-mediated responses in steroid metabolism were examined using a bovine endometrial epithelial culture system. Twenty singleton pregnant Holstein heifers were supplemented with 20 mg of melatonin (n = 10) or no melatonin supplementation (control; n = 10) from days 190 to 262 of gestation. Maternal measurements were recorded on days 180 (baseline), 210, 240, and 262 of gestation. Total uterine blood flow was increased by 25% in the MEL-treated heifers compared with the CON. Concentrations of progesterone were decreased in MEL vs CON heifers. Total serum antioxidant capacity was increased by 43% in MEL-treated heifers when compared with CON. Activity of cytochrome P450 1A, 2C, and superoxide dismutase was increased in bovine endometrial epithelial cells treated with melatonin, whereas the melatonin receptor antagonist, luzindole, negated the increase in cytochrome P450 2C activity. Moreover, estradiol or progesterone treatment altered bovine uterine melatonin receptor expression, which could potentiate the melatonin-mediated responses during late gestation. The observed increase in total uterine blood flow during melatonin supplementation could be related to its antioxidant properties. Compromised pregnancies are typically accompanied by increased oxidative stress; therefore, melatonin could serve as a therapeutic supplementation strategy. This could lead to further fetal programming implications in conjunction with offspring growth and development postnatally. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas.

    Science.gov (United States)

    Reiter, Russel J; Rosales-Corral, Sergio; Tan, Dun Xian; Jou, Mei Jie; Galano, Annia; Xu, Bing

    2017-11-01

    Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin's chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin's high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.

  6. Melatonin and Angelman Syndrome: Implications and Mathematical Model of Diurnal Secretion

    Directory of Open Access Journals (Sweden)

    Justyna Paprocka

    2017-01-01

    Full Text Available The main aim of the study was to compare the melatonin rhythms in subjects with Angelman syndrome (n=9 and in children with (n=80 and without (n=40 epilepsy (nonepileptic patients diagnosed with peripheral nerve palsies, myopathy, and back pain using our mathematical model of melatonin circadian secretion. The characteristics describing the diurnal hormone secretion such as minimum melatonin concentration, release amplitude, phase shift of melatonin release, and sleep duration as well as the dim light melatonin onset (DLMO of melatonin secretion and the γ shape parameter allow analyzing the fit and deducing about how much the measured melatonin profile differs from a physiological bell-shaped secretion. The estimated sleep duration and phase shift of melatonin release as well as the DMLO offsets at 25% and 50% relative thresholds are the key characteristic of Angelman syndrome children. As revealed from the γ shape parameter, the melatonin secretion profiles are disturbed in majority of the AG subjects revealing rather a triangular course instead of the bell-like one.

  7. Solubilization and purification of melatonin receptors from lizard brain

    International Nuclear Information System (INIS)

    Rivkees, S.A.; Conron, R.W. Jr.; Reppert, S.M.

    1990-01-01

    Melatonin receptors in lizard brain were identified and characterized using 125 I-labeled melatonin ([ 125 I]MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resulted in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography

  8. Solubilization and purification of melatonin receptors from lizard brain.

    Science.gov (United States)

    Rivkees, S A; Conron, R W; Reppert, S M

    1990-09-01

    Melatonin receptors in lizard brain were identified and characterized using 125I-labeled melatonin ([125I]MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resulted in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography.

  9. Detection of melatonin receptor mRNA in human muscle

    International Nuclear Information System (INIS)

    Li Lei

    2004-01-01

    To verify the expression of melatonin receptor mRNA in human, muscle, muscle beside vertebrae was collected to obtain total RNA and the mRNA of melatonin receptor was detected by RT-PCR method. The electrophoretic results of RT-PCR products by mt 1 and MT 2 primer were all positive and the sequence is corresponding with human melatonin receptor cDNA. It suggests that melatonin may act on the muscle beside vertebrae directly and regulate its growth and development. (authors)

  10. Melatonin-producing endophytic bacteria from grapevine roots promote the abiotic stress-induced production of endogenous melatonin in their hosts

    Directory of Open Access Journals (Sweden)

    Jian Jiao

    2016-09-01

    Full Text Available Endophytes form symbiotic relationships with plants and constitute an important source of phytohormones and bioactive secondary metabolites for their hosts. To date, most studies of endophytes have focused on the influence of these microorganisms on plant growth and physiology and their role in plant defenses against biotic and abiotic stressors; however, to the best of our knowledge, the ability of endophytes to produce melatonin has not been reported. In the present study, we isolated and identified root-dwelling bacteria from three grapevine varieties and found that, when cultured under laboratory conditions, some of the bacteria strains secreted melatonin and tryptophan-ethyl ester. The endophytic bacterium Bacillus amyloliquefaciens SB-9 exhibited the highest level of in vitro melatonin secretion and also produced three intermediates of the melatonin biosynthesis pathway: 5-hydroxytryptophan, serotonin, and N-acetylserotonin. After B. amyloliquefaciens SB-9 colonization, the plantlets exhibited increased plant growth. Additionally, we found that, in grapevine plantlets exposed to salt or drought stress, colonization by B. amyloliquefaciens SB-9 increased the upregulation of melatonin synthesis, as well as that of its intermediates, but reduced the upregulation of grapevine tryptophan decaboxylase genes (VvTDCs and a serotonin N-acetyltransferase gene (VvSNAT transcription, when compared to the un-inoculated control. Colonization by B. amyloliquefaciens SB-9 was also able to counteract the adverse effects of salt- and drought-induced stress by reducing the production of malondialdehyde and reactive oxygen species (H2O2 and O2− in roots. Therefore, our findings demonstrate the occurrence of melatonin biosynthesis in endophytic bacteria and provide evidence for a novel form of communication between beneficial endophytes and host plants via melatonin.

  11. Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.

    Science.gov (United States)

    Sheen, Jiunn-Ming; Chen, Yu-Chieh; Hsu, Mei-Hsin; Tain, You-Lin; Huang, Ying-Hsien; Tiao, Mao-Meng; Li, Shih-Wen; Huang, Li-Tung

    2016-08-20

    Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.

  12. Nocturnal Wakefulness is Associated with Next-Day Suicidal Ideation in Major Depression and Bipolar Disorder

    Science.gov (United States)

    Ballard, Elizabeth D.; Vande Voort, Jennifer L.; Bernert, Rebecca A.; Luckenbaugh, David A.; Richards, Erica M.; Niciu, Mark J.; Furey, Maura L.; Duncan, Wallace C.; Zarate, Carlos A.

    2016-01-01

    Objective Self-reported sleep disturbances may confer elevated risk for suicidal ideation, suicide attempts, and death. However, limited research has evaluated polysomnography (PSG)-determined sleep disturbance as an acute physiological risk factor for suicidal thoughts. This study sought to investigate the relationship between nocturnal wakefulness in association with next-day suicidal ideation using overnight PSG assessment from data collected between 2006 and 2013. Method Participants with DSM-IV-diagnosed major depressive disorder (MDD) or bipolar depression underwent overnight PSG monitoring in a sleep laboratory. The Hamilton Depression Rating Scale (HAM-D) was administered the morning after PSG recording to assess next-day suicidal ideation, severity of depressive symptoms, and subjective sleep disturbances. Results Using a generalized linear mixed model, a significant time-by-ideation interaction was found indicating greater nocturnal wakefulness at 4:00 AM among participants with suicidal ideation (F(4,136) = 3.65, p = .007). Increased time awake during the 4:00 AM hour (4:00 to 4:59) was significantly associated with elevated suicidal thoughts the next day (standardized β = .31, p = .008). This relationship persisted after controlling for age, gender, diagnosis, and severity of depressive symptoms. Conclusion Greater nocturnal wakefulness, particularly in the early morning hours, was significantly associated with next-day suicidal thoughts. PSG-documented sleep disruption at specific times of night may represent an acute risk factor of suicidal ideation that warrants additional research. Clinical Trials Identifier NCT00024635 PMID:27337418

  13. Termination of short term melatonin treatment in children with delayed Dim Light Melatonin Onset: effects on sleep, health, behavior problems, and parenting stress

    NARCIS (Netherlands)

    van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G.; Oort, Frans J.

    2011-01-01

    To investigate the effects of termination of short term melatonin treatment on sleep, health, behavior, and parenting stress in children with delayed Dim Light Melatonin Onset. Forty-one children (24 boys, 17 girls; mean age=9.43 years) entered melatonin treatment for 3 weeks and then discontinued

  14. Melatonin Secretion during a Short Nap Fosters Subsequent Feedback Learning

    Directory of Open Access Journals (Sweden)

    Christian D. Wiesner

    2018-01-01

    Full Text Available Sleep helps to protect and renew hippocampus-dependent declarative learning. Less is known about forms of learning that mainly engage the dopaminergic reward system. Animal studies showed that exogenous melatonin modulates the responses of the dopaminergic reward system and acts as a neuroprotectant promoting memory. In humans, melatonin is mainly secreted in darkness during evening hours supporting sleep. In this study, we investigate the effects of a short period of daytime sleep (nap and endogenous melatonin on reward learning. Twenty-seven healthy, adult students took part in an experiment, either taking a 90-min afternoon nap or watching videos (within-subject design. Before and after the sleep vs. wake interval, saliva melatonin levels and reward learning were measured, and in the nap condition, a polysomnogram was obtained. Reward learning was assessed using a two-alternative probabilistic reinforcement-learning task. Sleep itself and subjective arousal or valence had no significant effects on reward learning. However, this study showed for the first time that an afternoon nap can elicit a small but significant melatonin response in about 41% of the participants and that the magnitude of the melatonin response predicts subsequent reward learning. Only in melatonin responders did a short nap improve reward learning. The difference between melatonin-responders and non-responders occurred very early during learning indicating that melatonin might have improved working memory rather than reward learning. Future studies should use paradigms differentiating working memory and reward learning to clarify which aspect of human feedback learning might profit from melatonin.

  15. High levels of melatonin generated during the brewing process.

    Science.gov (United States)

    Garcia-Moreno, H; Calvo, J R; Maldonado, M D

    2013-08-01

    Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

    Shirazi Hosseinidokht, A.

    2007-01-01

    Complete text of publication follows. For the sake of improvement in radiation therapy, radiobiology plays a crucial role through explaining observed phenomena, and suggesting improvements to existing therapies. Due to the damaging effects of ionizing radiation, radiobiologists have long been interested in identifying novel, nontoxic, effective, and convenient compounds to protect humans against radiation induced normal tissue injuries. Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, has been documented to ameliorate the oxidative injuries due to ionizing radiation. This article reviews different features that make melatonin a potentially useful radioprotector. Moreover, based on radiobiological models we hypothesize that melatonin may postpone the saturation of repair enzymes which leads to repairing more induced damage by repair system and more importantly allows the use of higher doses of radiation during radiotherapy to get a better therapeutic ratio. The implications of the accumulated observations suggest by virtue of melatonin's radioprotective and anticancer effects; it is time to use it as a radioprotector both for radiation workers and patients suffering from cancer either alone for cancer inhibition or in combination with traditional radiotherapy for getting a favorable efficacy/toxicity ratio during the treatment. Although compelling evidence suggests that melatonin may be effective for a variety of disorders, the optimum dose of melatonin for human radioprotection is yet to be determined by further research. We propose that, in the future melatonin improve therapeutic ratio in radiation oncology.

  17. Melatonin as a potential anticarcinogen for non-small-cell lung cancer

    Science.gov (United States)

    Han, Jing; Wang, Dongjin; Di, Shouyin; Hu, Wei; Liu, Dong; Li, Xiaofei; Reiter, Russel J.; Yan, Xiaolong

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC. PMID:27102150

  18. Melatonin identified in meats and other food stuffs: potentially nutritional impact.

    Science.gov (United States)

    Tan, Dun-Xian; Zanghi, Brian M; Manchester, Lucien C; Reiter, Russel J

    2014-09-01

    Melatonin has been identified in primitive photosynthetic bacteria, fungi, plants, and animals including humans. Vegetables, fruits, cereals, wine, and beers all contain melatonin. However, the melatonin content in meats has not been reported previously. Here, for the first time, we report melatonin in meats, eggs, colostrum, and in other edible food products. The levels of melatonin measured by HPLC, in lamb, beef, pork, chicken, and fish, are comparable to other food stuffs (in the range of ng/g). These levels are significantly higher than melatonin concentrations in the blood of vertebrates. As melatonin is a potent antioxidant, its presence in the meat could contribute to shelf life duration as well as preserve their quality and taste. In addition, the consumption of these foods by humans or animals could have health benefits considering the important functions of melatonin as a potent free radical scavenger and antioxidant. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

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    Lemoine P

    2011-07-01

    Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

  20. PR-10 proteins as potential mediators of melatonin-cytokinin cross-talk in plants: crystallographic studies of LlPR-10.2B isoform from yellow lupine.

    Science.gov (United States)

    Sliwiak, Joanna; Sikorski, Michal; Jaskolski, Mariusz

    2018-04-06

    LlPR-10.2B, a Pathogenesis-related class 10 (PR-10) protein from yellow lupine (Lupinus luteus) was crystallized in complex with melatonin, an emerging important plant regulator and antioxidant. The structure reveals two molecules of melatonin bound in the internal cavity of the protein, plus a very well-defined electron density near the cavity entrance, corresponding to an unknown ligand molecule comprised of two flat rings, which is most likely a product of melatonin transformation. In a separate LlPR-10.2B co-crystallization experiment with an equimolar mixture of melatonin and trans-zeatin, which is a cytokinin phytohormone well recognized as a PR-10-binding partner, a quaternary 1 : 1 : 1 : 1 complex was formed, in which one of the melatonin-binding sites has been substituted with trans-zeatin, whereas the binding of melatonin at the second binding site and binding of the unknown ligand are undisturbed. This unusual complex, when compared with the previously described PR-10/trans-zeatin complexes and with the emerging structural information about melatonin binding by PR-10 proteins, provides intriguing insights into the role of PR-10 proteins in phytohormone regulation in plants, especially with the involvement of melatonin, and implicates the PR-10 proteins as low-affinity melatonin binders under the conditions of elevated melatonin concentration. Atomic coordinates and processed structure factors corresponding to the final models of the LlPR-10.2B/melatonin and LlPR-10.2B/melatonin + trans-zeatin complexes have been deposited with the Protein Data Bank (PDB) under the accession codes 5MXB and 5MXW. The corresponding raw X-ray diffraction images have been deposited in the RepOD Repository at the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM) of the University of Warsaw, Poland, and are available for download with the following Digital Object Identifiers (DOI): https://doi.org/10.18150/repod.9923638 and https://doi.org/10

  1. Melatonin improves spatial navigation memory in male diabetic rats

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    Farrin Babaei-Balderlou

    2012-09-01

    Full Text Available The aim of the present study was to evaluate the effect of melatonin as an antioxidant on spatial navigation memory in male diabetic rats. Thirty-two male white Wistar rats weighing 200 ± 20 g were divided into four groups, randomly: control, melatonin, diabetic and melatonin-treated diabetic. Experimental diabetes was induced by intraperitoneal injection of 50 mg kg-1 streptozotocin. Melatonin was injected (10 mg kg-1 day-1, ip for 2 weeks after 21 days of diabetes induction. At the end of administration period, the spatial navigation memory of rats was evaluated by cross-arm maze. In this study lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in hippocampus. Diabetes caused to significant decrease in alternation percent in the cross-arm maze, as a spatial memory index, compared to the control group (p < 0.05, whereas administration of melatonin prevented the spatial memory deficit in diabetic rats. Also melatonin injection significantly increased the spatial memory in intact animals compared to the control group (p < 0.05. Assessment of hippocampus homogenates indicated an increase in lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the diabetic group compared to the control animals, while melatonin administration ameliorated these indices in diabetic rats. In conclusion, diabetes induction leads to debilitation of spatial navigation memory in rats, and the melatonin treatment improves the memory presumably through the reduction of oxidative stress in hippocampus of diabetic rats.

  2. The Role of Melatonin in the Treatment of Primary Headache Disorders

    Science.gov (United States)

    Gelfand, Amy A.; Goadsby, Peter J.

    2016-01-01

    Objective To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders. Background Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness. Methods We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders. Results There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin’s role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache. Conclusions Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation. PMID:27316772

  3. Melatonin Improves the Photosynthetic Apparatus in Pea Leaves Stressed by Paraquat via Chlorophyll Breakdown Regulation and Its Accelerated de novo Synthesis

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    Katarzyna Szafrańska

    2017-05-01

    Full Text Available The positive effect of melatonin on the function of the photosynthetic apparatus is known, but little is known about the specific mechanisms of melatonin's action in plants. The influence of melatonin on chlorophyll metabolism of 24-day-old Pisum sativum L. seedlings during paraquat (PQ-induced oxidative stress was investigated in this study. Seeds were hydro-primed with water (H, 50 and 200 μM melatonin/water solutions (H-MEL50, H-MEL200, while non-primed seeds were used as controls (C. Increases in chlorophyllase activity (key enzyme in chlorophyll degradation and 5-aminolevulinic acid contents (the first compound in the porphyrin synthesis pathway were observed in H-MEL50 and H-MEL200 leaf disks. This suggests that melatonin may accelerate damaged chlorophyll breakdown and its de novo synthesis during the first hours of PQ treatment. Elevated level of pheophytin in control leaf disks following 24 h of PQ incubation probably was associated with an enhanced rate of chlorophyll degradation through formation of pheophytin as a chlorophyll derivative. This validates the hypothesis that chlorophyllide, considered for many years, as a first intermediate of chlorophyll breakdown is not. This is indicated by the almost unchanged chlorophyll to chlorophyllide ratio after 24 h of PQ treatment. However, prolonged effects of PQ-induced stress (48 h revealed extensive discolouration of control and water-treated leaf disks, while melatonin treatment alleviated PQ-induced photobleaching. Also the ratio of chlorophyll to chlorophyllide and porphyrin contents were significantly higher in plants treated with melatonin, which may indicate that this indoleamine both retards chlorophyll breakdown and stimulates its de novo synthesis during extended stress. We concluded that melatonin added into the seeds enhances the ability of pea seedlings to accelerate chlorophyll breakdown and its de novo synthesis before stress appeared and for several hours after, while

  4. Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

    Science.gov (United States)

    Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

    2011-04-01

    Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

  5. Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells.

    Science.gov (United States)

    He, Ruijun; Cui, Min; Lin, Hui; Zhao, Lei; Wang, Jiayu; Chen, Songfeng; Shao, Zengwu

    2018-04-15

    Intervertebral disc degeneration (IVDD) is thought to be the major cause of low back pain (LBP), which is still in lack of effective etiological treatment. Oxidative stress has been demonstrated to participate in the impairment of nucleus pulposus cells (NPCs). As the most important neuroendocrine hormone in biological clock regulation, melatonin (MLT) is also featured by good antioxidant effect. In this study, we investigated the effect and mechanisms of melatonin on oxidative stress-induced damage in rat NPCs. Cytotoxicity of H 2 O 2 and protecting effect of melatonin were analyzed with Cell Counting kit-8 (CCK-8). Cell apoptosis rate was detected by Annexin V-FITC/PI staining. DCFH-DA probe was used for the reactive oxygen species (ROS) detection. The mitochondrial membrane potential (MMP) changes were analyzed with JC-1 probe. Intracellular oxidation product and reductants were measured through enzymatic reactions. Extracellular matrix (ECM) and apoptosis associated proteins were analyzed with Western blot assays. Melatonin preserved cell viability of NPCs under oxidative stress. The apoptosis rate, ROS level and malonaldehyde (MDA) declined with melatonin. MLT/H 2 O 2 group showed higher activities of GSH and SOD. The fall of MMP receded and the expression of ECM protein increased with treatment of melatonin. The mitochondrial pathway of apoptosis was inhibited by melatonin. Melatonin alleviated the oxidative stress-induced apoptosis of NPCs. Melatonin could be a promising alternative in treatment of IVDD. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

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    Dun-Xian Tan

    2015-10-01

    Full Text Available Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.

  7. Melatonin attenuates thiocyanate-induced vasoconstriction in aortic rings

    Directory of Open Access Journals (Sweden)

    Alexander M. Prusa

    2017-11-01

    Full Text Available Cigarette smoking not only has a carcinogenic effect but also leads to an increase in arterial blood pressure. Besides its main components, i.e. nicotine, tar, and carbon monoxide, cigarette smoke also contains thiocyanate. Thiocyanate anions (SCN− arise from the detoxification of hydrogen cyanide and its plasma concentrations were found to correlate significantly with cigarette consumption. There is also evidence that atherosclerotic disease progression is much more rapid when serum SCN− levels are increased. Melatonin, a non-toxic indolamine with various physiologic functions, is believed to protect against inflammatory processes and oxidative stress. It has been demonstrated that melatonin serves as free radical scavenger and represents a potent antioxidant. Therefore, it is believed that melatonin with its atheroprotective effects may be useful either as a sole therapy or in conjunction with others. The aim of this study was to quantify the thiocyanate-induced vasomotor response in aortic tissue and further to examine the potential of melatonin in affecting the generated vasoreactivity. Aortic rings of adult male normotensive Wistar rats were cut into 4-mm rings. Following the administration of thiocyanate in various concentrations, vasomotor response of aortic vessel segments was measured. To assess the effect of melatonin on vasomotor activity, organ bath concentrations were modulated from 60 to 360 pM, which corresponds to physiologic plasma up to the levels of patients with regular oral intake of 3 mg of melatonin as a supplement. Thirty-six rat aortic rings were studied. When exposed to thiocyanate, vessel segments revealed vasoconstriction in a concentration-dependent manner. In rings which were preincubated with melatonin at a concentration of 360 pM, a 56.5% reduction of effect size could be achieved (4.09 ± 1.22 mN versus 9.41 ± 1.74 mN, P < 0.0001. Additionally, administration of 360 pM melatonin at a

  8. Melatonin as potential inducer of Th17 cell differentiation.

    Science.gov (United States)

    Kuklina, Elena M

    2014-09-01

    The subset of T lymphocytes producing IL-17 (Th17) plays a key role in the immune system. It has been implicated in host defense, inflammatory diseases, tumorigenesis, autoimmune diseases, and transplant rejection. Careful analysis of the data available holds that Th17 cell subpopulation should be under the direct control of pineal hormone melatonin: the key Th17 differentiation factor RORα serves in the meantime as a high-affinity melatonin receptor. Since the levels of melatonin have diurnal and seasonal variation, as well as substantial deviations in some physiological or pathological conditions, melatonin-dependent regulation of Th17 cells should implicate multiform manifestation, such as influencing the outcome of infectious challenge or determining predisposition, etiology and progression of immune-related morbidities. Another important reason to raise a point of the new melatonin effects is current considering the possibilities of its clinical trials. Especially, the differentiation of Th17 upon melatonin treatment must aggravate the current recession in autoimmune diseases or induce serious complications in pregnancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

    Science.gov (United States)

    Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

    2015-04-01

    Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

  10. Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats

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    Mayssaa M. Wahby

    2017-12-01

    Full Text Available Bisphenol A is one of the anthropogenic chemicals produced worldwide, currently released into the environment and causes endocrine-disruption. The largest environmental compartments of BPA are abiotic associated with water and suspended solids that becomes an integrated part of the food chain. The present study aimed to examine the possible protective role of Ginkgo biloba extract (GBE, melatonin and their combination against BPA-induced liver and kidney toxicity of male rats. Fifty rats were divided into five equal groups: control, BPA, BPA plus GBE, BPA plus melatonin and BPA plus GBE plus melatonin. The elevated activities of plasma ALT and AST in addition to increased levels of urea and creatinine concomitant with the decreased total plasma protein could reflect the injurious effect of BPA. Liver and kidney levels of TBARS were significantly increased, while GSH, SOD and GPX were decreased in BPA-treated rats. Also, CAT and GST activities were significantly disrupted in the liver and kidney of rats treated with BPA. Moreover, BPA significantly increased the proinflammatory cytokine TNF-α in the liver and kidney tissues. The histopathological analysis confirmed these results. All the previous alterations in the liver and kidney could be ameliorated when BPA-treated rats were co-administrated either with GBE, melatonin or their combination. These natural substances could exhibit protective effects against BPA-induced hepato- and nephrotoxicity owing to their antioxidative and anti-inflammatory potentials. Keywords: Bisphenol A, Ginkgo biloba extract, Melatonin, Lipid peroxidation, Antioxidant enzymes, Histopathological analysis

  11. Nocturnal drainage wind characteristics in two converging air sheds

    International Nuclear Information System (INIS)

    Gedayloo, T.; Clements, W.E.; Barr, S.; Archuleta, J.A.

    1980-01-01

    During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 25 0 C during summer and about 20 0 C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s -1 and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin

  12. Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells.

    Science.gov (United States)

    Altındal, Damla Çetin; Gümüşderelioğlu, Menemşe

    2016-02-01

    Melatonin loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and microparticles in the diameter of ∼200 nm and 3.5 μm, respectively, were prepared by emulsion-diffusion-evaporation method. Melatonin entrapment into the particles was significantly improved with the addition of 0.2% (w/v) melatonin into the aqueous phase and encapsulation efficiencies were found as 14 and 27% for nanoparticles and microparticles, respectively. At the end of 40 days, ∼70% of melatonin was released from both of particles, with high burst release. Both blank and melatonin loaded PLGA nanoparticles caused toxic effect on the MG-63 cells due to their uptake by the cells. However, when 0.05 mg microparticle that is carrying ∼1.7 μg melatonin was added to the cm(2) of culture, inhibitory effect of melatonin on the cells were obviously observed. The results would provide an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma by encapsulating it into a polymeric carrier system.

  13. Effect of mobile usage on serum melatonin levels among medical students.

    Science.gov (United States)

    Shrivastava, Abha; Saxena, Yogesh

    2014-01-01

    Exposure to extremely low frequency (ELF) electromagnetic radiations from mobile phones may affect the circadian rhythm of melatonin in mobile users. The study was designed with objective to evaluate the influence of mobile phone on circadian rhythm of melatonin and to find the association if any between the hours of mobile usage with serum melatonin levels. All the volunteers medical students using mobiles for > 2 hrs/day were included in high users group and volunteers who used mobile for ≤ 2 hrs where included in low users group. Both high and low users volunteers were sampled three times in the same day (Morning-3-4 am, Noon 1-2 pm, Evening-5-6 pm) for estimation of serum melatonin levels: Comparsion of sernum melatonin levels in high users and low users were done by Mann Whitney "U" Test. Reduced morning melatonin levels (3-4 am) was observed in high users (> 2 hrs/day) i.e high users had a disturbed melatonin circadian rhythm.There was a negative correlation between melatonin secretion and hours of mobile usages.

  14. Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders.

    Science.gov (United States)

    Sagrillo-Fagundes, Lucas; Assunção Salustiano, Eugênia Maria; Yen, Philippe Wong; Soliman, Ahmed; Vaillancourt, Cathy

    2016-01-01

    Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.

  15. Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

    Science.gov (United States)

    Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

    2000-06-01

    The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

  16. Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells.

    Science.gov (United States)

    Shu, Tao; Wu, Tao; Pang, Mao; Liu, Chang; Wang, Xuan; Wang, Juan; Liu, Bin; Rong, Limin

    2016-06-03

    Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay

    Directory of Open Access Journals (Sweden)

    Katsuura Tetsuo

    2011-01-01

    Full Text Available Abstract Background Although various acceptable and easy-to-use devices have been used for saliva collection, cotton swabs are among the most common ones. Previous studies reported that cotton swabs yield a lower level of melatonin detection. However, this statistical method is not adequate for detecting an agreement between cotton saliva collection and passive saliva collection, and a test for bias is needed. Furthermore, the effects of cotton swabs have not been examined at lower melatonin level, a level at which melatonin is used for assessment of circadian rhythms, namely dim light melatonin onset (DLMO. In the present study, we estimated the effect of cotton swabs on the results of salivary melatonin assay using the Bland-Altman plot at lower level. Methods Nine healthy males were recruited and each provided four saliva samples on a single day to yield a total of 36 samples. Saliva samples were directly collected in plastic tubes using plastic straws, and subsequently pipetted onto cotton swabs (cotton saliva collection and into clear sterile tubes (passive saliva collection. The melatonin levels were analyzed in duplicate using commercially available ELISA kits. Results The mean melatonin concentration in cotton saliva collection samples was significantly lower than that in passive saliva collection samples at higher melatonin level (>6 pg/mL. The Bland-Altman plot indicated that cotton swabs causes relative and proportional biases in the assay results. For lower melatonin level ( Conclusion Our findings indicate an interference effect of cotton swabs on the assay result of salivary melatonin at lower melatonin level. Cotton-based collection devices might, thus, not be suitable for assessment of DLMO.

  18. Nocturnal Wakefulness Is Associated With Next-Day Suicidal Ideation in Major Depressive Disorder and Bipolar Disorder.

    Science.gov (United States)

    Ballard, Elizabeth D; Vande Voort, Jennifer L; Bernert, Rebecca A; Luckenbaugh, David A; Richards, Erica M; Niciu, Mark J; Furey, Maura L; Duncan, Wallace C; Zarate, Carlos A

    2016-06-01

    Self-reported sleep disturbances may confer elevated risk for suicidal ideation, suicide attempts, and death. However, limited research has evaluated polysomnographically determined sleep disturbance as an acute physiologic risk factor for suicidal thoughts. This study sought to investigate the relationship between nocturnal wakefulness in association with next-day suicidal ideation using overnight polysomnography assessment from data collected between 2006 and 2013. Sixty-five participants with DSM-IV-diagnosed major depressive disorder or bipolar depression underwent overnight polysomnography monitoring in a sleep laboratory. The Hamilton Depression Rating Scale (HDRS) was administered the morning after polysomnography recording to assess next-day suicidal ideation, severity of depressive symptoms, and subjective sleep disturbances. Using a generalized linear mixed model, a significant time-by-ideation interaction was found indicating greater nocturnal wakefulness at 4:00 am among participants with suicidal ideation (F4,136 = 3.65, P = .007). Increased time awake during the 4:00 am hour (4:00 to 4:59) was significantly associated with elevated suicidal thoughts the next day (standardized β = 0.31, P = .008). This relationship persisted after controlling for age, gender, diagnosis, and severity of depressive symptoms. Greater nocturnal wakefulness, particularly in the early morning hours, was significantly associated with next-day suicidal thoughts. Polysomnographically documented sleep disruption at specific times of night may represent an acute risk factor of suicidal ideation that warrants additional research. ClinicalTrials.gov identifier: NCT00024635. © Copyright 2016 Physicians Postgraduate Press, Inc.

  19. Melatonin Promotes the In Vitro Development of Microinjected Pronuclear Mouse Embryos via Its Anti-Oxidative and Anti-Apoptotic Effects.

    Science.gov (United States)

    Tian, Xiuzhi; Wang, Feng; Zhang, Lu; Ji, Pengyun; Wang, Jing; Lv, Dongying; Li, Guangdong; Chai, Menglong; Lian, Zhengxing; Liu, Guoshi

    2017-05-05

    CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats) combined with pronuclear microinjection has become the most effective method for producing transgenic animals. However, the relatively low embryo developmental rate limits its application. In the current study, it was observed that 10 -7 M melatonin is considered an optimum concentration and significantly promoted the in vitro development of murine microinjected pronuclear embryos, as indicated by the increased blastocyst rate, hatching blastocyst rate and blastocyst cell number. When these blastocysts were implanted into recipient mice, the pregnancy rate and birth rate were significantly higher than those of the microinjected control, respectively. Mechanistic studies revealed that melatonin treatment reduced reactive oxygen species (ROS) production and cellular apoptosis during in vitro embryo development and improved the quality of the blastocysts. The implantation of quality-improved blastocysts led to elevated pregnancy and birth rates. In conclusion, the results revealed that the anti-oxidative and anti-apoptotic activities of melatonin improved the quality of microinjected pronuclear embryos and subsequently increased both the efficiency of embryo implantation and the birth rate of the pups. Therefore, the melatonin supplementation may provide a novel alternative method for generating large numbers of transgenic mice and this method can probably be used in human-assisted reproduction and genome editing.

  20. Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence.

    Science.gov (United States)

    Goradel, Nasser Hashemi; Asghari, Mohammad Hossein; Moloudizargari, Milad; Negahdari, Babak; Haghi-Aminjan, Hamed; Abdollahi, Mohammad

    2017-11-15

    Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis. Melatonin prevents translocation of HIF-1α into the nucleus thereby hindering VEGF expression and also prevents the formation of HIF-1α, phospho-STAT3 and CBP/p300 complex which is involved in the expression of angiogenesis-related genes. Angiostatic properties of melatonin could be also due to its ability to inhibit VEGFR2's activation and expression. Other angiostatic mechanisms of melatonin include the inhibition of endothelial cell migration, invasion, and tube formation. In the present study, we have reviewed the molecular anti-angiogenesis pathways mediated by melatonin and the responsible mechanisms in various types of cancers both in vitro and in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Exogenous melatonin administration is beneficial for male ...

    African Journals Online (AJOL)

    ABSTRACT. Background: A concern in the use of exogenous melatonin as a therapeutic intervention is that it may interfere with reproductive function. Herein, we report that chronic exogenous melatonin administration does not impair male reproductive function during ageing and at old age in male Sprague Dawley rats.

  3. Increased nocturnal blood pressure in enuretic children with polyuria.

    Science.gov (United States)

    Kruse, Anne; Mahler, Birgitte; Rittig, Soren; Djurhuus, Jens Christian

    2009-10-01

    We investigated the association between nocturnal blood pressure and urine production in children with enuresis. A total of 39 consecutive children with a mean age of 9.8 years (range 6.2 to 14.9) with monosymptomatic nocturnal enuresis completed a bladder diary, including 2 weeks of basic documentation and 2 with desmopressin titration from 120 to 240 microg sublingually. Arterial blood pressure was measured every 30 minutes during 24 hours and during 4 additional nights using an ambulatory blood pressure monitor. Furthermore, 10 healthy children were recruited into the study who completed a bladder diary for 5 days while measuring arterial blood pressures with documentation of all intake and voided volumes. Patients with nocturnal polyuria had significantly higher nocturnal mean arterial pressure than patients without polyuria and controls (p polyuria than in children without polyuria. There was a significant positive correlation between average nocturnal mean arterial pressure and nocturnal urine volume in the whole study. The association between nocturnal blood pressure and urine volume, and the role of blood pressure should be investigated in a larger group of children with enuresis who have nocturnal polyuria.

  4. Melatonin prevents experimental preterm labor and increases offspring survival.

    Science.gov (United States)

    Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M

    2014-03-01

    Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

    Science.gov (United States)

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-12-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Melatonin: a protective and detoxifying agent in paraquat toxicity

    International Nuclear Information System (INIS)

    Ghanem, M.; Gad, H.; Hanan; Aziz, A.; Nasr, M.

    2002-01-01

    The ability of melatonin as a protective and detoxifying agent against paraquat-induced oxidative damage in rat lungs and liver was examined. Changes in reduced glutathione (OSH) concentration and malonaldehyde (MDA) level were measured. Pathological examination to lungs and liver was done. Paraquat in 2 doses (20,70 mg/kg) was injected I.P. into rats with melatonin (10 mg/kg) I. P. either before and after paraquat intoxication or only after it. Melatonin proved its protective role when given before and after paraquat intoxication more than its detoxifying effect when given only after paraquat. The biochemical improvement following melatonin therapy was more evident than the histopathological one. (author)

  7. Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay.

    Science.gov (United States)

    Kozaki, Tomoaki; Lee, Soomin; Nishimura, Takayuki; Katsuura, Tetsuo; Yasukouchi, Akira

    2011-01-10

    Although various acceptable and easy-to-use devices have been used for saliva collection, cotton swabs are among the most common ones. Previous studies reported that cotton swabs yield a lower level of melatonin detection. However, this statistical method is not adequate for detecting an agreement between cotton saliva collection and passive saliva collection, and a test for bias is needed. Furthermore, the effects of cotton swabs have not been examined at lower melatonin level, a level at which melatonin is used for assessment of circadian rhythms, namely dim light melatonin onset (DLMO). In the present study, we estimated the effect of cotton swabs on the results of salivary melatonin assay using the Bland-Altman plot at lower level. Nine healthy males were recruited and each provided four saliva samples on a single day to yield a total of 36 samples. Saliva samples were directly collected in plastic tubes using plastic straws, and subsequently pipetted onto cotton swabs (cotton saliva collection) and into clear sterile tubes (passive saliva collection). The melatonin levels were analyzed in duplicate using commercially available ELISA kits. The mean melatonin concentration in cotton saliva collection samples was significantly lower than that in passive saliva collection samples at higher melatonin level (>6 pg/mL). The Bland-Altman plot indicated that cotton swabs causes relative and proportional biases in the assay results. For lower melatonin level (<6 pg/mL), although the BA plots didn't show proportional and relative biases, there was no significant correlation between passive and cotton saliva collection samples. Our findings indicate an interference effect of cotton swabs on the assay result of salivary melatonin at lower melatonin level. Cotton-based collection devices might, thus, not be suitable for assessment of DLMO.

  8. Melatonin and its correlation with testosterone in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Priyanka Jain

    2013-01-01

    Full Text Available Context: Polycystic ovarian syndrome (PCOS is considered to be the most common endocrine disorder affecting women. Melatonin, a small lipophilic indoleamine, and reproductive hormones may be interrelated. Melatonin influences sex steroid production at different stages of ovarian follicular maturation as melatonin receptors have been demonstrated at multiple sites in ovary and in intrafollicular fluid. It plays role as an antioxidant and free radical scavanger which protects follicles from oxidative stress, rescuing them from atresia, leading to complete follicular maturation and ovulation. Aims: To study the role of melatonin in PCOS and to investigate its correlation with testosterone in patients suffering from PCOS. Settings and Design: A total of 50 women with PCOS (Rotterdam criteria, 2003 and 50 age and weight matched healthy controls were selected and serum melatonin estimation was done in both the groups and correlated with serum total testosterone levels. Materials and Methods: In a case-control study, detailed history, clinical examination and hormonal evaluation [basal levels of leutinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, insulin, total testosterone, progesterone and melatonin] were carried out in all the participants including both cases and controls. For melatonin estimation, blood samples were collected between 12:00 am and 04:00 am on day 2 nd of menstrual cycle and analyzed by using commercially available enzyme-linked immunosorbent assay kit. Statistical Analysis: Student′s t-test was used to compare the significant difference in mean values between cases and control groups. Chi-square test was used to test the significant association between the qualitative variables. Linear correlation coefficient and regression analysis were done to see the amount and direction of relationship between quantitative variables. Results: The mean melatonin level was observed to be significantly

  9. Effect of melatonin on in vitro maturation of bovine oocytes ...

    African Journals Online (AJOL)

    ... Vs 17.67, 15.68, 16.53). In conclusion in this experiment, melatonin cannot improve cumulus cell expansion and nuclear maturation of bovine oocytes. When concentrations is high, melatonin may affect bovine oocytes meiotic maturation at metaphase-1 stage, but it is improbable melatonin be toxic for bovine oocytes.

  10. Exogenous melatonin administration is beneficial for male ...

    African Journals Online (AJOL)

    Background: A concern in the use of exogenous melatonin as a therapeutic intervention is that it may interfere with reproductive function. Herein, we report that chronic exogenous melatonin administration does not impair male reproductive function during ageing and at old age in male Sprague Dawley rats. Methods: ...

  11. Presence of melatonin in various cat brainstem nuclei determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Sallanon, M.; Touret, M.; Claustrat, B.

    1982-01-01

    Microdissected samples of juvenile cat brain tissue were assayed for melatonin content using a double antibody radioimmunoassay. Immunoreactive melatonin was consistently detected, albeit in variable amounts, in pineal, habenula, the region of the nucleus gracilis, gigantocellular reticular formation of the pons and medulla oblongata. Among the negative areas were raphe nuclei, substantia nigra dn locus caeruleus. These findings suggest that melatonin may play a role in some structures of the central nervous system outside the pineal-hypothalamo-pituitary axis. This immunoreactive melatonin could reflect a local synthesis, or a tissular uptake of melatonin from blood or cerebrospinal fluid. (author)

  12. Melatonin Regulates Oxidative Stress Initiated by Freund’s Complete Adjuvant

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2015-07-01

    Full Text Available Melatonin is a hormone with strong antioxidant properties. In this experiment, Freund’s complete adjuvant was used as a stressogenic substance given to laboratory outbred mice, whereas melatonin was investigated as a protectant against the stressogenic effect. Levels of low molecular weight antioxidants, thiobarbituric acid reactive substances, and tumor necrosis factor α and activity of glutathione reductase were determined in blood from the animals. Surprisingly, melatonin was not involved in direct regulation of antioxidants, thiobarbituric acid reactive substances and tumor necrosis factor α. On the other hand, melatonin regulated glutathione reductase activity. We can conclude on regulation of metabolism caused by melatonin in the model. The effect was more important than the expected regulation of immunity and basal oxidative homeostasis.

  13. Intermittent nocturnal hypoxia and metabolic risk in obese adolescents with obstructive sleep apnea.

    Science.gov (United States)

    Narang, Indra; McCrindle, Brian W; Manlhiot, Cedric; Lu, Zihang; Al-Saleh, Suhail; Birken, Catherine S; Hamilton, Jill

    2018-01-22

    There is conflicting data regarding the independent associations of obstructive sleep apnea (OSA) with metabolic risk in obese youth. Previous studies have not consistently addressed central adiposity, specifically elevated waist to height ratio (WHtR), which is associated with metabolic risk independent of body mass index. The objective of this study was to determine the independent effects of the obstructive apnea-hypopnea index (OAHI) and associated indices of nocturnal hypoxia on metabolic function in obese youth after adjusting for WHtR. Subjects had standardized anthropometric measurements. Fasting blood included insulin, glucose, glycated hemoglobin, alanine transferase, and aspartate transaminase. Insulin resistance was quantified with the homeostatic model assessment. Overnight polysomnography determined the OAHI and nocturnal oxygenation indices. Of the 75 recruited subjects, 23% were diagnosed with OSA. Adjusting for age, gender, and WHtR in multivariable linear regression models, a higher oxygen desaturation index was associated with a higher fasting insulin (coefficient [standard error] = 48.076 [11.255], p Intermittent nocturnal hypoxia rather than the OAHI was associated with metabolic risk in obese youth after adjusting for WHtR. Measures of abdominal adiposity such as WHtR should be considered in future studies that evaluate the impact of OSA on metabolic health.

  14. Melatonin and breast cancer: Evidences from preclinical and human studies.

    Science.gov (United States)

    Kubatka, Peter; Zubor, Pavol; Busselberg, Dietrich; Kwon, Taeg Kyu; Adamek, Mariusz; Petrovic, Daniel; Opatrilova, Radka; Gazdikova, Katarina; Caprnda, Martin; Rodrigo, Luis; Danko, Jan; Kruzliak, Peter

    2018-02-01

    The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Protective effects of melatonin on long-term administration of fluoxetine in rats.

    Science.gov (United States)

    Khaksar, Majid; Oryan, Ahmad; Sayyari, Mansour; Rezabakhsh, Aysa; Rahbarghazi, Reza

    2017-10-02

    The degree and consequence of tissue injury are highly regarded during long-term exposure to selective antidepressant fluoxetine. Melatonin has been shown to palliate different lesions by scavenging free radicals, but its role in the reduction of the fluoxetine-induced injuries has been little known. Thirty-six mature male Wistar rats were randomly assigned into control and experimental groups. The experimental rats were included as following; 24mg/kg/bw fluoxetine for 4 weeks; 1mg/kg/bw melatonin for 4 weeks; fluoxetine+1-week melatonin, fluoxetine+2-week melatonin and fluoxetine+4-week melatonin. In the current experiment, we investigated weight gain, hematological and biochemical parameters, pathological injuries and oxidative status. We noted the positive effect of melatonin in weight loss of fluoxetine-treated rats (pfluoxetine were reversed by melatonin (pfluoxetine (pfluoxetine in inducing leukopenia, thrombocytopenia and hypochromic and macrocytic anemia which was blunted by melatonin. Both RBCs and platelets indices were also corrected. Rats received melatonin in combination with fluoxetine showed a reduction in the severity of degeneration and inflammatory changes in different tissues, brain, heart, liver, lungs, testes and kidneys as compared to the fluoxetine group. Therefore, melatonin fundamentally reversed the side effects of fluoxetine in the rat model which is comparable to human medicine. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis.

    Science.gov (United States)

    Jaworek, Jolanta; Leja-Szpak, Anna; Nawrot-Porąbka, Katarzyna; Szklarczyk, Joanna; Kot, Michalina; Pierzchalski, Piotr; Góralska, Marta; Ceranowicz, Piotr; Warzecha, Zygmunt; Dembinski, Artur; Bonior, Joanna

    2017-05-08

    Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N ¹-acetyl- N ¹-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

  17. Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jolanta Jaworek

    2017-05-01

    Full Text Available Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK. Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1 Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2 Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3 In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

  18. Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

    Science.gov (United States)

    Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C.; Domeniconi, Raquel F.; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F.; Reiter, Russel J.; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A.

    2017-01-01

    Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy. PMID:28398226

  19. Melatonin: Action as antioxidant and potential applications in human disease and aging

    International Nuclear Information System (INIS)

    Bonnefont-Rousselot, Dominique; Collin, Fabrice

    2010-01-01

    This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

  20. The effect of the melatonin on cryopreserved mouse testicular cells

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2016-01-01

    Full Text Available Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 μm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

  1. A radiobiological review on melatonin. A novel radioprotector

    International Nuclear Information System (INIS)

    Shirazi, A.; Ghobadi, G.; Ghazi-Khansari, M.

    2007-01-01

    In spite of the fact that radiotherapy is a common and effective tool for cancer treatment; the radio sensitivity of normal tissues adjacent to the tumor which are unavoidably exposed to radiation limits therapeutic gain. For the sake of improvement in radiation therapy, radiobiology- the study of the action of ionizing radiation on living things- plays a crucial role through explaining observed phenomena, and suggesting improvements to existing therapies. Due to the damaging effects of ionizing radiation, radiobiologists have long been interested in identifying novel, nontoxic, effective, and convenient compounds to protect humans against radiation induced normal tissue injuries. In hundreds of investigations, melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, has been documented to ameliorate the oxidative injuries due to ionizing radiation. This article reviews different features that make melatonin a potentially useful radioprotector. Moreover, based on radiobiological models we can hypothesize that melatonin may postpone the saturation of repair enzymes which leads to repairing more induced damage by repair system and more importantly allows the use of higher doses of radiation during radiotherapy to get a better therapeutic ratio. The implications of the accumulated observations suggest by virtue of melatonin's radioprotective and anticancer effects; it is time to use it as a radioprotector both for radiation workers and patients suffering from cancer either alone for cancer inhibition or in combination with traditional radiotherapy for getting a favorable efficacy/toxicity ratio during the treatment. Although compelling evidence suggests that melatonin may be effective for a variety of disorders, the optimum dose of melatonin for human radioprotection is yet to be determined. We propose that, in the future, melatonin improve the therapeutic ratio in radiation oncology. (author)

  2. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

    Science.gov (United States)

    Liu, Shangming; Guo, Yuji; Yuan, Qiuhuan; Pan, Yan; Wang, Liyan; Liu, Qian; Wang, Fuwu; Wang, Jingjing; Hao, Aijun

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Melatonin in sleepless children : everything has a rhythm?

    NARCIS (Netherlands)

    van Geijlswijk, I.M.

    2011-01-01

    Every living organism has an biological clock regulating endogenous melatonin production, synchronized by exogenous impulses like daylight, temperature and feeding. Inappropriately applied bright light disturbs this melatonin rhythm. Some large swine producers apply artificial light three times a

  4. Roles of Melatonin in Fetal Programming in Compromised Pregnancies

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Chen

    2013-03-01

    Full Text Available Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.

  5. Roles of Melatonin in Fetal Programming in Compromised Pregnancies

    Science.gov (United States)

    Chen, Yu-Chieh; Sheen, Jiunn-Ming; Tiao, Miao-Meng; Tain, You-Lin; Huang, Li-Tung

    2013-01-01

    Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. PMID:23466884

  6. The effects of adenotonsillotomy on nocturnal enuresis in snoring children

    Directory of Open Access Journals (Sweden)

    Marta Kostrzewa

    2017-12-01

    Full Text Available Introduction: Nocturnal enuresis is a common problem in the paediatric population. A number of reports indicate that there is a relationship between sleep-disordered breathing in children with tonsillar hypertrophy and nocturnal enuresis. Restoration of nasopharyngeal patency may eliminate nocturnal enuresis. Aim: The aim of the study was to evaluate the incidence of nocturnal enuresis in children snoring due to nasopharyngeal lymphatic tissue hypertrophy as well as to assess the effects of restored upper respiratory patency by means of adenectomy and tonsillectomy on the resolution of nocturnal enuresis in children. Material and methods: The study included 50 children with sleep-disordered breathing qualified for adenectomy, tonsillotomy or adenotonsillotomy (median age 7 years. The control group consisted of 20 healthy children (median age 8 years. Children in the study group were assessed prior to surgical procedure as well as 3 and 6 months after surgery. The presence of sleep-disordered breathing and nocturnal enuresis was determined based on author’s questionnaire completed by parents. Results: The incidence of nocturnal enuresis in children with nasopharyngeal lymphatic tissue hypertrophy was 18% (M:F 17%:19%; p > 0.05. Nocturnal enuresis was still reported in 6% of children 3 months after tonsillotomy. The disorder resolved in all girls and 97% of boys 6 months after procedure. Conclusions: Sleep-disordered breathing in children with nasopharyngeal lymphatic tissue hypertrophy is associated with nocturnal enuresis. Restoration of nasopharyngeal patency in these patients eliminates nocturnal enuresis. Tonsillar hypertrophy causing obstructive breathing should be included in the differential diagnosis of nocturnal enuresis.

  7. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    Science.gov (United States)

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. The Australian Bogong Moth Agrotis infusa: A Long-Distance Nocturnal Navigator

    Directory of Open Access Journals (Sweden)

    Eric Warrant

    2016-04-01

    Full Text Available The nocturnal Bogong moth (Agrotis infusa is an iconic and well-known Australian insect that is also a remarkable nocturnal navigator. Like the Monarch butterflies of North America, Bogong moths make a yearly migration over enormous distances, from southern Queensland, western and northwestern New South Wales (NSW and western Victoria, to the alpine regions of NSW and Victoria. After emerging from their pupae in early spring, adult Bogong moths embark on a long nocturnal journey towards the Australian Alps, a journey that can take many days or even weeks and cover over 1000 km. Once in the Alps (from the end of September, Bogong moths seek out the shelter of selected and isolated high ridge-top caves and rock crevices (typically at elevations above 1800 m. In hundreds of thousands, moths line the interior walls of these cool alpine caves where they “hibernate” over the summer months (referred to as “estivation”. Towards the end of the summer (February and March, the same individuals that arrived months earlier leave the caves and begin their long return trip to their breeding grounds. Once there, moths mate, lay eggs and die. The moths that hatch in the following spring then repeat the migratory cycle afresh. Despite having had no previous experience of the migratory route, these moths find their way to the Alps and locate their estivation caves that are dotted along the high alpine ridges of southeastern Australia. How naïve moths manage this remarkable migratory feat still remains a mystery, although there are many potential sensory cues along the migratory route that moths might rely on during their journey, including visual, olfactory, mechanical and magnetic cues. Here we review our current knowledge of the Bogong moth, including its natural history, its ecology, its cultural importance to the Australian Aborigines and what we understand about the sensory basis of its long-distance nocturnal migration. From this analysis it becomes

  9. Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.

    Science.gov (United States)

    Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

    2014-04-01

    Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  10. Vibrational and electronic spectroscopic studies of melatonin

    Science.gov (United States)

    Singh, Gurpreet; Abbas, J. M.; Dogra, Sukh Dev; Sachdeva, Ritika; Rai, Bimal; Tripathi, S. K.; Prakash, Satya; Sathe, Vasant; Saini, G. S. S.

    2014-01-01

    We report the infrared absorption and Raman spectra of melatonin recorded with 488 and 632.8 nm excitations in 3600-2700 and 1700-70 cm-1 regions. Further, we optimized molecular structure of the three conformers of melatonin within density functional theory calculations. Vibrational frequencies of all three conformers have also been calculated. Observed vibrational bands have been assigned to different vibrational motions of the molecules on the basis of potential energy distribution calculations and calculated vibrational frequencies. Observed band positions match well with the calculated values after scaling except Nsbnd H stretching mode frequencies. It is found that the observed and calculated frequencies mismatch of Nsbnd H stretching is due to intermolecular interactions between melatonin molecules.

  11. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo.

    Science.gov (United States)

    Itani, Nozomi; Skeffington, Katie L; Beck, Christian; Niu, Youguo; Giussani, Dino A

    2016-01-01

    There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy. © 2015 The Authors. Journal of Pineal Research. Published by John Wiley & Sons Ltd.

  12. A systematic review of peri-operative melatonin

    DEFF Research Database (Denmark)

    Andersen, L P H; Werner, M U; Rosenberg, J

    2014-01-01

    We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction......%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements....

  13. Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality.

    Science.gov (United States)

    Udo, Yukihiro; Nakao, Masahiro; Honjo, Hisashi; Ukimura, Osamu; Kawauchi, Akihiro; Kitakoji, Hiroshi; Miki, Tsuneharu

    2011-03-01

    • To determine the relationship between the number of nocturia and 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration as well as to assess the significance of these factors with respect to eliminating nocturnal voidings in individual patients with nocturia. • Among 532 participants who completed a 3-day bladder diary between April 2005 and December 2006, the diaries of 450 participants without 24-h polyuria were analyzed. • Clinical variables such as the number of daytime and night-time voids, 24-h urine volume, nocturnal polyuria index, daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep duration and proportion of night/day urine production rates were obtained from each diary. • Participants were classified into eight groups according to values of three factors: nocturnal MVV, proportion of night/day urine production rates and length of sleep duration. • Each group was divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more). • The data from non-nocturics with three normal factors were regarded as the normal control and compared with the variables of the other subgroups using Dunnett's method. • Variables that form the basis of classifying participants into eight groups and corresponding to abnormal factors of each group were statistically significant in all the subgroups of each group. • Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of the group with three normal factors. • A significantly decreased 24-h urine volume was found in non-nocturics of groups with nocturnal polyuria, decreased bladder capacity and both long sleep duration and nocturnal polyuria. • A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of the groups

  14. Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

    Science.gov (United States)

    Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

    2015-01-01

    The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

  15. Nocturnal bees are attracted by widespread floral scents.

    Science.gov (United States)

    Carvalho, Airton Torres; Maia, Artur Campos Dalia; Ojima, Poliana Yumi; dos Santos, Adauto A; Schlindwein, Clemens

    2012-03-01

    Flower localization in darkness is a challenging task for nocturnal pollinators. Floral scents often play a crucial role in guiding them towards their hosts. Using common volatile compounds of floral scents, we trapped female nocturnal Megalopta-bees (Halictidae), thus uncovering olfactory cues involved in their search for floral resources. Applying a new sampling method hereby described, we offer novel perspectives on the investigation of nocturnal bees.

  16. Melatonin as a treatment for mood disorders: a systematic review.

    Science.gov (United States)

    De Crescenzo, F; Lennox, A; Gibson, J C; Cordey, J H; Stockton, S; Cowen, P J; Quested, D J

    2017-12-01

    Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders. We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo. Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study. There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Melatonin redirects carbohydrates metabolism during sugar starvation in plant cells.

    Science.gov (United States)

    Kobylińska, Agnieszka; Borek, Sławomir; Posmyk, Małgorzata M

    2018-05-01

    Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin efficacy eliminates oxidative stress (direct and indirect antioxidant) and moreover induce plant stress reaction and switch on different defence strategies (preventively and interventively actions). In this report, the impact of exogenous melatonin on carbohydrate metabolism in Nicotiana tabacum L. line Bright Yellow 2 (BY-2) suspension cells during sugar starvation was examined. We analysed starch concentration, α-amylase and PEPCK activity as well as proteolytic activity in culture media. It has been shown that BY-2 cell treatment with 200 nM of melatonin improved viability of sugar-starved cells. It was correlated with higher starch content and phosphoenolpyruvate carboxykinase (PEPCK) activity. The obtained results revealed that exogenous melatonin under specific conditions (stress) can play regulatory role in sugar metabolism, and it may modulate carbohydrate concentration in etiolated BY-2 cells. Moreover, our results confirmed the hypothesis that if the starch is synthesised even in sugar-starved cells, it is highly probable that melatonin shifts the BY-2 cell metabolism on gluconeogenesis pathway and allows for synthesis of carbohydrates from nonsugar precursors, that is amino acids. These points to another defence strategy that was induced by exogenous melatonin applied in plants to overcome adverse environmental conditions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Melatonin in Apples and Juice: Inhibition of Browning and Microorganism Growth in Apple Juice.

    Science.gov (United States)

    Zhang, Haixia; Liu, Xuan; Chen, Ting; Ji, Yazhen; Shi, Kun; Wang, Lin; Zheng, Xiaodong; Kong, Jin

    2018-02-27

    Synthetic melatonin ( N -acetyl-5-methoxytryptamine, MT) is popular in the US and Asian markets as a health supplement. Here, we identified a naturally occurring melatonin source in apple juice. Melatonin was present in all 18 apple cultivars tested. The highest melatonin level of the edible part of apple was detected in the apple peel. The melatonin content in 'Fuji' apple juice is comparable to the level of its flesh. Melatonin was consumed during the process of juicing due to its interaction with the oxidants. Melatonin addition significantly reduced the juice color change to brown (browning). The mechanism is that melatonin scavenges the free radicals, which was indicated by the ASBT analysis; therefore, inhibiting the conversion of o -diphenolic compounds into quinones. Most importantly, melatonin exhibited powerful anti-microorganism activity in juice. The exact mechanisms of this action are currently unknown. These effects of melatonin can preserve the quality and prolong the shelf life of apple juice. The results provide valuable information regarding commerciall apple juice processing and storage.

  19. Melatonin in Apples and Juice: Inhibition of Browning and Microorganism Growth in Apple Juice

    Directory of Open Access Journals (Sweden)

    Haixia Zhang

    2018-02-01

    Full Text Available Synthetic melatonin (N-acetyl-5-methoxytryptamine, MT is popular in the US and Asian markets as a health supplement. Here, we identified a naturally occurring melatonin source in apple juice. Melatonin was present in all 18 apple cultivars tested. The highest melatonin level of the edible part of apple was detected in the apple peel. The melatonin content in ‘Fuji’ apple juice is comparable to the level of its flesh. Melatonin was consumed during the process of juicing due to its interaction with the oxidants. Melatonin addition significantly reduced the juice color change to brown (browning. The mechanism is that melatonin scavenges the free radicals, which was indicated by the ASBT analysis; therefore, inhibiting the conversion of o-diphenolic compounds into quinones. Most importantly, melatonin exhibited powerful anti-microorganism activity in juice. The exact mechanisms of this action are currently unknown. These effects of melatonin can preserve the quality and prolong the shelf life of apple juice. The results provide valuable information regarding commerciall apple juice processing and storage.

  20. Effects of melatonin and bright light treatment in childhood chronic sleep onset insomnia with late melatonin onset: A randomised controlled study

    NARCIS (Netherlands)

    van Maanen, A.; Meijer, A.M.; Smits, M.G.; van der Heijden, K.B.; Oort, F.J.

    2017-01-01

    STUDY OBJECTIVES: Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages

  1. Pathophysiology of nocturnal lower urinary tract symptoms in older patients with urinary incontinence.

    Science.gov (United States)

    Denys, Marie-Astrid; Decalf, Veerle; Kumps, Candy; Petrovic, Mirko; Goessaert, An-Sofie; Everaert, Karel

    2017-11-01

    To explore the mismatch between functional bladder capacity and nocturnal urine production, and to study the pathophysiology of an increased nocturnal urine production in older patients with urinary incontinence. The present prospective observational study included adults aged ≥65 years with urinary incontinence. Participants completed questionnaires, frequency volume charts and renal function profiles. The nocturnal lower urinary tract symptom index was defined as nocturnal urine output/maximum voided volume; the nocturnal polyuria index as nocturnal/24 h urine output. The median age (n = 95) was 74 years (69-79), 87% were women and 73% had nocturnal lower urinary tract symptoms (nocturnal urinary incontinence or nocturia ≥2). Participants with nocturnal lower urinary tract symptoms had a significantly higher nocturnal urine output (809 mL vs 650 mL; P = 0.001) and no significant difference in maximum voided volume (350 mL vs 437 mL; P = 0.079) compared with participants without nocturnal lower urinary tract symptoms. Participants (nocturnal polyuria index >33% [n = 56], nocturnal polyuria index >40% [n = 42], nocturnal lower urinary tract symptom index >1.87 [n = 51]) showed higher night-time diuresis rates, free water and sodium clearance compared with during the daytime. Controls (nocturnal polyuria index ≤33% [n = 26], nocturnal polyuria index ≤40% [n = 40], nocturnal lower urinary tract symptom index ≤1.87 [n = 44]) had no circadian rhythm in their diuresis rate or sodium clearance, but more nocturnal free water clearance compared with during the daytime. The majority of older adults with urinary incontinence present nocturnal lower urinary tract symptoms. An increased nocturnal sodium diuresis seems to be the only mechanism differentiating patients with nocturnal lower urinary tract symptoms from controls. © 2017 The Japanese Urological Association.

  2. Glutamatergic clock output stimulates melatonin synthesis at night

    NARCIS (Netherlands)

    Perreau-Lenz, Stéphanie; Kalsbeek, Andries; Pévet, Paul; Buijs, Ruud M.

    2004-01-01

    The rhythm of melatonin synthesis in the rat pineal gland is under the control of the biological clock, which is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence of the SCN on melatonin synthesis, by using

  3. Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation.

    Science.gov (United States)

    Soliman, Ahmed; Lacasse, Andrée-Anne; Lanoix, Dave; Sagrillo-Fagundes, Lucas; Boulard, Véronique; Vaillancourt, Cathy

    2015-08-01

    Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation-induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and β-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Eye and heart morphogenesis are dependent on melatonin signaling in chick embryos.

    Science.gov (United States)

    Nogueira, Renato C; Sampaio, Lucia de Fatima S

    2017-10-15

    Calmodulin is vital for chick embryos morphogenesis in the incubation time 48-66 h when the rudimentary C-shaped heart attains an S-shaped pattern and the optic vesicles develop into optic cups. Melatonin is in the extraembryonic yolk sac of the avian egg; melatonin binds calmodulin. The aim of this study was to investigate the function of melatonin in the formation of the chick embryo optic cups and S-shaped heart, by pharmacological methods and immunoassays. Mel1a melatonin receptor immunofluorescence was distributed in the optic cups and rudimentary hearts. We separated embryonated chicken eggs at 48 h of incubation into basal, control and drug-treated groups, with treatment applied in the egg air sac. At 66 h of incubation, embryos were excised from the eggs and analyzed. Embryos from the basal, control (distilled water), melatonin and 6-chloromelatonin (melatonin receptor agonist) groups had regular optic cups and an S-shaped heart, while those from the calmidazolium (calmodulin inhibitor) group did not. Embryos from the luzindole (melatonin receptor antagonist) and prazosin (Mel1c melatonin receptor antagonist) groups did not have regular optic cups. Embryos from the 4-P-PDOT (Mel1b melatonin receptor antagonist) group did not have an S-shaped heart. Previous application of the melatonin, 6-chloromelatonin or forskolin (adenylate cyclase enhancer) prevented the abnormal appearance of chick embryos from the calmidazolium, luzindole, prazosin and 4-P-PDOT groups. However, 6-chloromelatonin and forskolin only partially prevented the development of defective eye cups in embryos from the calmidazolium group. The results suggested that melatonin modulates chick embryo morphogenesis via calmodulin and membrane receptors. © 2017. Published by The Company of Biologists Ltd.

  5. Melatonin for women in pregnancy for neuroprotection of the fetus.

    Science.gov (United States)

    Wilkinson, Dominic; Shepherd, Emily; Wallace, Euan M

    2016-03-29

    Melatonin is an antioxidant with anti-inflammatory and anti-apoptotic effects. Animal studies have supported a fetal neuroprotective role for melatonin when administered maternally. It is important to assess whether melatonin, given to the mother, can reduce the risk of neurosensory disabilities (including cerebral palsy) and death, associated with fetal brain injury, for the preterm or term compromised fetus. To assess the effects of melatonin when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016). We planned to include randomised controlled trials and quasi-randomised controlled trials comparing melatonin given to women in pregnancy (regardless of the route, timing, dose and duration of administration) for fetal neuroprotection with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of melatonin. Two review authors planned to independently assess trial eligibility, trial quality and extract the data. We found no randomised trials for inclusion in this review. One study is ongoing. As we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage.Although evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm.Further high-quality research is needed and research

  6. Adverse effects of melatonin on rat pups of Wistar-Kyoto dams receiving melatonin supplementation during pregnancy.

    Science.gov (United States)

    Singh, Harbindar Jeet; Keah, Lee Siew; Kumar, Arun; Sirajudeen, K N S

    2012-11-01

    This report documents an incidental finding during a study investigating the effects of melatonin supplementation on the development of blood pressure in SHR. Administration of 10 mg/kg/day of melatonin in drinking water during pregnancy to Wistar-Kyoto (WKY) dams caused a loss of more than 50% of the pups by the age of three weeks and 95% by the age of 6 weeks. There was no maternal morbidity or mortality in the two strains or death of any of the SHR pups. No obvious physical defects were present but mean body weight was lower in the surviving WKY rats when compared to that of melatonin supplemented SHR or non-supplemented WKY pups. The reason for the high mortality in WKY pups is uncertain and appears to be strain if not batch specific. There is a need for caution in its use, particularly during pregnancy, and clearly necessitates more detailed studies. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings

    Directory of Open Access Journals (Sweden)

    Jun Ni

    2018-03-01

    Full Text Available Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione content and the GSH/GSSG (oxidized glutathione ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX and superoxide dismutase (SOD, but not catalase (CAT and peroxidase (POD, were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat.

  8. Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings.

    Science.gov (United States)

    Ni, Jun; Wang, Qiaojian; Shah, Faheem Afzal; Liu, Wenbo; Wang, Dongdong; Huang, Shengwei; Fu, Songling; Wu, Lifang

    2018-03-30

    Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat.

  9. Exogenous Melatonin for Sleep Problems in Individuals with Intellectual Disability: A Meta-Analysis

    Science.gov (United States)

    Braam, Wiebe; Smits, Marcel G.; Didden, Robert; Korzilius, Hubert; van Geijlswijk, Ingeborg M.; Curfs, Leopold M. G.

    2009-01-01

    Recent meta-analyses on melatonin has raised doubts as to whether melatonin is effective in treating sleep problems in people without intellectual disabilities. This is in contrast to results of several trials on melatonin in treating sleep problems in individuals with intellectual disabilities. To investigate the efficacy of melatonin in treating…

  10. Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Kloster; Mielke, Louise Vennegaard

    2016-01-01

    BACKGROUND: Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. OBJECTIVE: The aim of this study was to estimate...... the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. METHODS: The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative...... treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption...

  11. Melatonin and Ischemic Stroke: Mechanistic Roles and Action

    Directory of Open Access Journals (Sweden)

    Syed Suhail Andrabi

    2015-01-01

    Full Text Available Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

  12. Melatonin and Ischemic Stroke: Mechanistic Roles and Action.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2015-01-01

    Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca(2+) level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

  13. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

    Science.gov (United States)

    Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J; Peng, Jie; Turek, Fred W; Marconi, Angelica; Rademaker, Alfred W; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C

    2014-04-01

    Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further

  14. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS?

    Science.gov (United States)

    Kim, Mi Kyoung; Park, Eun A; Kim, Hyung Joon; Choi, Won Yun; Cho, Jung Hyun; Lee, Woo Sik; Cha, Kwang Yul; Kim, You Shin; Lee, Dong Ryul; Yoon, Tae Ki

    2013-01-01

    Human pre-ovulatory follicular fluid (FF) contains a higher concentration of melatonin than serum. The aim of this study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcomes of an in-vitro maturation (IVM) IVF-embryo transfer programme for patients with polycystic ovarian syndrome (PCOS). Melatonin concentrations in the culture media of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes after using IVM media with or without melatonin were analysed. In the culture media of GC or COC, melatonin concentrations gradually increased. When human chorionic gonadotrophin priming protocols were used, implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control group (PPregnancy rates were also higher, although not significantly. The findings suggest that the addition of melatonin to IVM media may improve the cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes. It is speculated that follicular melatonin may be released from luteinizing GC during late folliculogenesis and that melatonin supplementation may be used to improve the clinical outcomes of IVM IVF-embryo transfer. Melatonin is primarily produced by the pineal gland and regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. Interestingly, human pre-ovulatory follicular fluid contains a higher concentration of melatonin than serum. However, in contrast to animal studies, the direct role of melatonin on oocyte maturation in the human system has not yet been investigated. So, the aim of the study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcome of an in-vitro maturation (IVM) IVF-embryo transfer programme for PCOS patients. The melatonin concentrations in culture medium of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the

  15. Melatonin, a potential effective protector in whole body γ-irradiated rats

    International Nuclear Information System (INIS)

    Tawfik, S.S; El-Nashar, D.E; Ahmed, M.M; Hanafy, Z.E

    2010-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), the chief hormone of pineal gland, is widely distributed in animal kingdom. It is claimed for its antioxidant and free radical properties. The present study aimed to examine the radio protective potentiality and efficacy of melatonin against damages induced in whole body γ-irradiated rats. Animals received melatonin (10 mg/ kg body wt/ day) for 10 successive days pre-exposure to 3 Gy of γ-radiation (acute dose). Rats sacrificed at 10 and 20 days post the irradiation time. The results revealed that the prolonged administration of melatonin has ameliorated the radiation- induced depletion in brain, testis and serum glutathione (GSH) level and a decrease in serum glutathione peroxidase (GPX) activity when compared with their matched values in irradiated rats. In addition, remarkable decreases in the concentration of lipid peroxidation (LPO) product; malondialdhyde (MDA) was observed in brain, testis and serum of rats received melatonin pre-radiation exposure. As well as, significant decreases in disulphide glutathione (GSSG) were observed in serum.Histopathological examination of brain and testis showed that administration of melatonin pre-irradiation according to the present regimen has attenuated radiation induced tissue damages and improved tissue architecture. Cytogenetically, the chromosomal aberration (CA) assay in bone marrow pointed out a significant difference between rats received melatonin pre-irradiation and γ-irradiated rats in most CA types. Accordingly, it could be postulated the tissue diversity and cytogenetic impact of the administrated melatonin against acute ion syndrome in rat model.

  16. Alleviation of cold damage to photosystem II and metabolisms by melatonin in Bermudagrass

    Directory of Open Access Journals (Sweden)

    Jibiao eFan

    2015-11-01

    Full Text Available As a typical warm-season grass, Bermudagrass [Cynodon dactylon (L.Pers.] is widely applied in turf systems and animal husbandry. However, cold temperature is a key factor limiting resource utilization for Bermudagrass. Therefore, it is relevant to study the mechanisms by which Burmudagrass responds to cold. Melatonin is a crucial animal and plant hormone that is responsible for plant abiotic stress responses. The objective of this study was to investigate the role of melatonin in cold stress response of Bermudagrass. Wild Bermudagrass pre-treated with 100 μM melatonin was subjected to different cold stress treatments (-5 °C for 8 h with or without cold acclimation. The results showed lower malondialdehyde (MDA and electrolyte leakage (EL values, higher levels of chlorophyll, and greater superoxide dismutase and peroxidase activities after melatonin treatment than those in non-melatonin treatment under cold stress. Analysis of chlorophyll a revealed that the chlorophyll fluorescence transient (OJIP curves were higher after treatment with melatonin than that of non-melatonin treated plants under cold stress. The values of photosynthetic fluorescence parameters increased after treatment with melatonin under cold stress. The analysis of metabolism showed alterations in 46 metabolites in cold-stressed plants after melatonin treatment. Among the measured metabolites, five sugars (arabinose, mannose, glucopyranose, maltose, turanose and one organic acid (propanoic acid were significantly increased. However, valine and threonic acid contents were reduced in melatonin-treated plants. In summary, melatonin maintained cell membrane stability, increased antioxidant enzymes activities, improved the process of photosystem II, and induced alterations in Bermudagrass metabolism under cold stress.

  17. Structural Characteristics of Nocturnal Mesoscale Convective Systems in the U.S. Great Plains as Observed During the PECAN Field Campaign

    Science.gov (United States)

    Bodine, D. J.; Dougherty, E.; Rasmussen, K. L.; Torres, A. D.

    2015-12-01

    During the summer in the U.S. Great Plains, some of the heaviest precipitation falls from large thunderstorm complexes known as Mesoscale Convective Systems (MCSs). These frequently occurring MCSs are often nocturnal in nature, so the dynamics associated with these systems are more elusive than those in the daytime. The Plains Elevated Convection at Night (PECAN) field campaign was launched over a 7-week period as an endeavor to better understand nocturnal MCSs occurring in the Great Plains. PECAN featured a dense array of ground-based and airborne instruments to observe nocturnal MCS, including dual-polarization radars at multiple frequencies, mobile mesonets, and sounding units. Our role in PECAN involved deploying Ott Parsivel disdrometers to gain information on drop size distributions (DSDs) and fall speeds. Analysis of disdrometer data in conjunction with radar data presented using Contour Frequency by Altitude Diagrams (CFADs) and high-resolution radiosonde data allows for a structural comparison of PECAN MCS cases to previously identified MCS archetypes. Novel insights into the structural evolution of nocturnal MCSs in relation to their synoptic, mesoscale, and thermodynamic environments are presented, using data collected from dense and numerous observation platforms. Understanding the environmental conditions that result in different nocturnal MCS configurations is useful for gaining insight into precipitation distributions and potential severe weather and flooding hazards in the Great Plains.

  18. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-01-01

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  19. Anxiolytisk, analgetisk og sedativ effekt af melatonin i den perioperative fase

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Rosenberg, Jacob; Gögenur, Ismail

    2011-01-01

    Melatonin is a hormone mainly produced in the pineal gland. The most well known effect is a modulation of the circadian rhythm. Patients undergoing surgery often get a disruption of this rhythm. Effects of melatonin have been examined in several randomised clinical studies. In this report we...... briefly review evidence regarding anxiolytical, analgesic and sedative effects of melatonin in relation to surgery. Studies show an effect in favour of medication with melatonin with regards to sedation and anxiety but the effect on analgesia has yet to be clarified with further clinical studies....

  20. Melatonin: new applications in clinical and veterinary medicine, plant physiology and industry.

    Science.gov (United States)

    Reiter, Russel J; Coto-Montes, Ana; Boga, Jose Antonio; Fuentes-Broto, Lorena; Rosales-Corral, Sergio; Tan, Duan-Xian

    2011-01-01

    Novel functions of melatonin continue to be uncovered. Those summarized in this report include actions at the level of the peripheral reproductive organs and include functions as an antioxidant to protect the maturing oocyte in the vesicular follicle and during ovulation, melatonin actions on the developing fetus particularly in relation to organizing the circadian system, its potential utility in combating the consequences of pre-eclampsia, reducing intrauterine growth restriction, suppressing endometriotic growths and improving the outcomes of in vitro fertilization/embryo transfer. The inhibitory effects of melatonin on many cancer types have been known for decades. Until recently, however, melatonin had not been tested as a protective agent against exocrine pancreatic tumors. This cancer type is highly aggressive and 5 year survival rate in individuals with pancreatic cancer is very low. Recent studies with melatonin indicate it may have utility in the treatment of these otherwise almost untreatable pancreatic cancers. The discovery of melatonin in plants has also opened a vast new field of research which is rapidly being exploited although the specific functions(s) of melatonin in plant organs remains enigmatic. Finally, the described application of melatonin's use as a chemical reductant in industry could well serve as a stimulus to further define the utility of this versatile molecule in new industrial applications.

  1. Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression.

    Science.gov (United States)

    Cui, Peilin; Yu, Minghua; Peng, Xingchun; Dong, Lv; Yang, Zhaoxu

    2012-03-01

    Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti-angiogenic capability is urgent in clinical practice. In this study, a co-culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC-1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co-cultured with PANC-1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC-1 cells. In addition, the VEGF mRNA expression was also down-regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co-culturing them with PANC-1 cells; this was associated with a suppression of VEGF expression in PANC-1 cells. © 2011 John Wiley & Sons A/S.

  2. Impact of melatonin supplementation in the rat spermatogenesis subjected to forced swimming exercise.

    Science.gov (United States)

    Moayeri, A; Mokhtari, T; Hedayatpour, A; Abbaszadeh, H-A; Mohammadpour, S; Ramezanikhah, H; Shokri, S

    2018-04-01

    Oxygen consumption increases many times during exercise, which can increase reactive oxygen species. It negatively affects fertility in male athletes. Melatonin is exerting a regulatory role at different levels of the hypothalamic-pituitary-gonadal axis. However, there is no evidence that the protective effects of melatonin persist after long duration exercise on the spermatogenesis. Therefore, this study was conducted to examine the impacts of melatonin on the testis following the administration of swimming exercise. Rats were separated into five different groups, including Control, sham M: received the solvent of melatonin, M: received melatonin, S: the exercise protocol, MS: received melatonin and the exercise protocol. After 8 weeks, animals were scarified and antioxidant enzymes levels of testes, spermatogenic cells apoptosis and sperm quality were measured. Swimming decreased all parameters of spermatozoa. Nevertheless, melatonin could significantly improve the progressive motility of spermatozoa in MS rats. Swimming caused an increased apoptosis of S group and decreased all antioxidant enzymes. Melatonin could drastically reduce apoptosis and increased these enzymes. Therefore, melatonin seems to induce the production of antioxidant enzymes of testicular tissues and diminish the extent of apoptotic changes caused by forced exercise on the testis, which can, in turn, ameliorate the sperm parameters. © 2017 Blackwell Verlag GmbH.

  3. Chronomedicine and type 2 diabetes: shining some light on melatonin.

    Science.gov (United States)

    Forrestel, Andrew C; Miedlich, Susanne U; Yurcheshen, Michael; Wittlin, Steven D; Sellix, Michael T

    2017-05-01

    In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in

  4. Dose dependent sun protective effect of topical melatonin

    DEFF Research Database (Denmark)

    Scheuer, Cecilie; Pommergaard, Hans-Christian; Rosenberg, Jacob

    2016-01-01

    BACKGROUND: Ultraviolet radiation (UVR) by sunlight results in an increasing number of skin conditions. Earlier studies have suggested a protective effect of topical treatment with the pineal hormone melatonin. However, this protective effect has never been evaluated in natural sunlight......-blind study in healthy volunteers. Twenty-three healthy volunteers, 8 male and 15 female, were enrolled. The protective effect of three different doses of melatonin cream (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight was tested. All participants had their backs exposed to sun from 1:22 PM.......5% concentrations. CONCLUSION: Application of melatonin cream 12.5% protects against natural sunlight induced erythema....

  5. Color indirect effects on melatonin regulation

    Science.gov (United States)

    Mian, Tian; Liu, Timon C.; Li, Yan

    2002-04-01

    Color indirect effect (CIE) is referred to as the physiological and psychological effects of color resulting from color vision. In previous papers, we have studied CIE from the viewpoints of the integrated western and Chinese traditional medicine, put forward the color-autonomic- nervous-subsystem model (CAM), and provided its time-theory foundation. In this paper, we applied it to study light effects on melatonin regulation in humans, and suggested that it is CIE that mediates light effects on melatonin suppression.

  6. Melatonin protects against maternal obesity-associated oxidative stress and meiotic defects in oocytes via the SIRT3-SOD2-dependent pathway.

    Science.gov (United States)

    Han, Longsen; Wang, Haichao; Li, Ling; Li, Xiaoyan; Ge, Juan; Reiter, Russel J; Wang, Qiang

    2017-10-01

    Maternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high-fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice. Oral administration of melatonin to HFD mice not only reduces ROS generation, but also prevents spindle/chromosome anomalies in oocytes, consequently promoting the developmental potential of early embryos. Consistent with this finding, we find that melatonin supplement during in vitro maturation also markedly attenuates oxidative stress and meiotic defects in HFD oocytes. Finally, by performing morpholino knockdown and acetylation-mimetic mutant overexpression assays, we reveal that melatonin ameliorates maternal obesity-induced defective phenotypes in oocytes through the SIRT3-SOD2-dependent mechanism. In sum, our data uncover the marked beneficial effects of melatonin on oocyte quality from obese females; this opens a new area for optimizing culture system as well as fertility management. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Serum melatonin levels in survivor and non-survivor patients with traumatic brain injury.

    Science.gov (United States)

    Lorente, Leonardo; Martín, María M; Abreu-González, Pedro; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor

    2017-07-19

    Circulating levels of melatonin in patients with traumatic brain injury (TBI) have been determined in a little number of studies with small sample size (highest sample size of 37 patients) and only were reported the comparison of serum melatonin levels between TBI patients and healthy controls. As to we know, the possible association between circulating levels of melatonin levels and mortality of patients with TBI have not been explored; thus, the objective of our current study was to determine whether this association actually exists. This multicenter study included 118 severe TBI (Glasgow Coma Scale melatonin, malondialdehyde (to assess lipid peroxidation) and total antioxidant capacity (TAC) at day 1 of severe TBI. We used mortality at 30 days as endpoint. We found that non-survivor (n = 33) compared to survivor (n = 85) TBI patients showed higher circulating levels of melatonin (p melatonin levels predicted 30-day mortality (Odds ratio = 1.334; 95% confidence interval = 1.094-1.627; p = 0.004), after to control for GCS, CT findings and age. We found a correlation between serum levels of melatonin levels and serum levels of TAC (rho = 0.37; p melatonin levels in patients with severe TBI. The main findings were that non-survivors had higher serum melatonin levels than survivors, and the association between serum levels of melatonin levels and mortality, peroxidation state and antioxidant state.

  8. Nocturnal Oviposition Behavior of Forensically Important Diptera in Central England.

    Science.gov (United States)

    Barnes, Kate M; Grace, Karon A; Bulling, Mark T

    2015-11-01

    Timing of oviposition on a corpse is a key factor in entomologically based minimum postmortem interval (mPMI) calculations. However, there is considerable variation in nocturnal oviposition behavior of blow flies reported in the research literature. This study investigated nocturnal oviposition in central England for the first time, over 25 trials from 2011 to 2013. Liver-baited traps were placed in an urban location during control (diurnal), and nocturnal periods and environmental conditions were recorded during each 5-h trial. No nocturnal activity or oviposition was observed during the course of the study indicating that nocturnal oviposition is highly unlikely in central England. © 2015 American Academy of Forensic Sciences.

  9. Melatonin: current status and future perspectives in plant science

    Directory of Open Access Journals (Sweden)

    Muhammad Azher Nawaz

    2016-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine is a ubiquitous molecule with pleiotropic actions in different organisms. It performs many important functions in human, animals and plants; these range from regulating circadian rhythms in animals to controlling senescence in plants. In this review, we summarize the available information regarding the presence of melatonin in different plant species, along with highlighting its biosynthesis and mechanisms of action. We also collected the available information on the effects of melatonin application on commercially important crops to improve their growth and development. Additionally, we have identified many new aspects where melatonin may have possible roles in plants, for example, its function in improving the storage life and quality of fruits and vegetables, its role in vascular reconnection during the grafting process and nutrient uptake from roots by modifying root architecture. Another potentially important aspect is the production of melatonin-rich food crops (cereals, fruits and vegetables through combination of conventional and modern breeding approaches, to increase plant resistance against biotic and abiotic stress, leading to improved crop yields and the nutraceutical value of produce to solve food security issues.

  10. Melatonin: Bone Metabolism in Oral Cavity

    Directory of Open Access Journals (Sweden)

    Fanny López-Martínez

    2012-01-01

    Full Text Available Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000 may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981. Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005 and Steflik et al. (1994. These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991.

  11. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

    Science.gov (United States)

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-09-07

    To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P sleep deprivation.

  12. Melatonin receptors: latest insights from mouse models

    Science.gov (United States)

    Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

    2014-01-01

    Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

  13. Immunoregulatory action of melatonin. The mechanism of action and the effect on inflammatory cells

    Directory of Open Access Journals (Sweden)

    Sylwia Mańka

    2016-10-01

    Full Text Available Literature data indicate a significant immunoregulatory role of melatonin. Melatonin exerts an effect directly affecting leucocytes bearing specific melatonin receptors or indirectly by means of melatonin regulating other hormones, opioids or cytokines. Despite numerous experiments, the influence of the hormone on the immune system is still controversial. Melatonin affects the immune response acting as both an activator and an inhibitor of the inflammatory process. The hormone acts as an “immunological buffer” activating impaired immunity in immunosuppression, chronic stress or old age as well as suppressing overreaction of the immune system. Melatonin mediates between neurohormonal and immune systems by means of the immune-pineal axis acting as a negative feedback mechanism. The axis connects development of the immune reaction with pineal activity and melatonin secretion induced by inflammatory mediators. The seasonal and circadian fluctuation of the melatonin level and the fluctuation related changes of the immune parameters can be responsible for some autoimmune and infectious diseases. In spite of that, there is a growing number of papers suggesting considerable therapeutic potential of melatonin in inflammatory disease treatment. This paper presents well-systematized information on the mechanism of melatonin action and its influence on cells involved in the inflammatory process – neutrophils and monocytes.

  14. Melatonin accelerates maturation inducing hormone (MIH): induced oocyte maturation in carps.

    Science.gov (United States)

    Chattoraj, Asamanja; Bhattacharyya, Sharmistha; Basu, Dipanjan; Bhattacharya, Shelley; Bhattacharya, Samir; Maitra, Saumen Kumar

    2005-02-01

    The present communication is an attempt to demonstrate the influence of melatonin on the action of maturation inducing hormone (MIH) on the maturation of oocytes in carps. The oocytes from gravid female major carp Labeo rohita were isolated and incubated separately in Medium 199 containing (a) only MIH (1 microg/ml), (b) only melatonin (at concentrations of 50, 100 or 500 pg/ml), and (c) both melatonin and MIH, but at different time intervals. In the latter group, melatonin was added to the incubating medium either (i) 4 h before addition of MIH, (ii) 2 h before addition of MIH, (iii) co-administered with MIH (0 h interval) or (iv) 2 h after addition of MIH. In each case, oocytes were further incubated for 4, 8, 12 or 16 h post- administration of MIH, and the effects of treatment on oocyte maturation were evaluated by considering the rate (%) of germinal vesicle breakdown (GVBD). Incubation of oocytes in a medium containing only melatonin did not result in GVBD of any oocyte. Nearly all the oocytes underwent GVBD when incubated with MIH for 16 h. Administration of melatonin along with MIH (at 0 h interval) or 2 h after addition of MIH did not result in any significant change in the rate of GVBD compared to that in a medium containing only MIH. However, it was quite interesting to observe that incubation of oocytes with melatonin especially 4 h prior to addition of MIH in the medium, led to an accelerated rate of GVBD in the oocytes. Experiments with the oocytes of another major carp Cyprinus carpio following an identical schedule depicted similar results except a difference in the optimum melatonin dose. In L. rohita, 50 pg/ml melatonin had maximum acceleratory effect on MIH-induced GVBD of oocytes, while it was 100 pg/ml in C. carpio. Further study revealed that pre-incubation with melatonin accelerates the action of MIH on the formation of a complex of two proteins (MPF), a regulatory component called cyclin B and the catalytic component protein kinase known as

  15. The effect of melatonin on mouse jejunal crypt cell survival and apoptosis

    International Nuclear Information System (INIS)

    Kang, Jin Oh; Ha, Eun Young; Baik, Hyung Hwan; Cho, Yong Ho; Hong, Seong Eon

    2000-01-01

    To evaluate protective mechanism of melatonin against radiation damage and its relationship with apoptosis in mouse jejunum. 168 mice were divided into 28 groups according to radiation dose and melatonin treatment. To analysis crypt survival, microcolony survival assay was done according to Withers and Elkind's method. To analysis apoptosis, TUNEL assay was done according to Labet-Moleur's method. Radiation protection effect of melatonin was demonstrated by crypt survival assay and its effect was stronger in high radiation dose area. Apoptosis index with 8 Gy irradiation was 18.4% in control group and 16.5% in melatonin treated group. After 18 Gy, apoptosis index was 17.2%in control group and 15.4% in melatonin treated group. Apoptosis index did not show statistically significant difference between melatonin shows clear protective effect in mouse jejunum against radiation damage but its protective effect seems not to be related with apoptosis protection effect

  16. Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

    Science.gov (United States)

    Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

    2017-10-01

    Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

  17. Nocturnal Gastroesophageal Reflux Revisited by Impedance-pH Monitoring

    Science.gov (United States)

    Blondeau, Kathleen; Mertens, Veerle; Tack, Jan; Sifrim, Daniel

    2011-01-01

    Background/Aims Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. Methods Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. Results Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. Conclusions Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux. PMID:21602991

  18. Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells.

    Science.gov (United States)

    Gu, Junyi; Lu, Zhongsheng; Ji, Chenghong; Chen, Yuchao; Liu, Yuzhao; Lei, Zhe; Wang, Longqiang; Zhang, Hong-Tao; Li, Xiangdong

    2017-09-01

    Melatonin, an indolamine mostly synthesized in the pineal gland, exerts the anti-cancer effect by various mechanisms in glioma cells. Our previous study showed that miR-155 promoted glioma cell proliferation and invasion. However, the question of whether melatonin may inhibit glioma by regulating miRNAs has not yet been addressed. In this study, we found that melatonin (100μM, 1μM and 1nM) significantly inhibited the expression of miR-155 in human glioma cell lines U87, U373 and U251. Especially, the lowest expression of miR-155 was detected in 1μM melatonin-treated glioma cells. Melatonin (1μM) inhibits cell proliferation of U87 by promoting cell apoptosis. Nevertheless, melatonin had no effect on cell cycle distribution of U87 cells. Moreover, U87 cells treated with 1μM melatonin presented significantly lower migration and invasion ability when compared with control cells. Importantly, melatonin inhibited c-MYB expression, and c-MYB knockdown reduced miR-155 expression and migration and invasion in U87 cells. Taken together, for the first time, our findings show that melatonin inhibits miR-155 expression and thereby represses glioma cell proliferation, migration and invasion, and suggest that melatonin may downregulate the expression of miR-155 via repression of c-MYB. This will provide a theoretical basis for revealing the anti-glioma mechanisms of melatonin. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Biological functions of melatonin in relation to pathogenesis of oral lichen planus.

    Science.gov (United States)

    Chaiyarit, Ponlatham; Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda

    2017-07-01

    Oral lichen planus (OLP) is considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Accumulated data support the involvement of cell-mediated immune dysfunction in the development of OLP. However, the connection between neuroendocrine system and oral immune response in OLP patients has never been clarified. Melatonin is considered as a major chronobiotic hormone produced mainly by the pineal gland. This gland is recognized as a regulator of circadian rhythm and a sensor in the immune response through the NF-kB transduction pathway. It was suggested that pineal-derived melatonin and extra-pineal melatonin synthesized at the site of inflamed lesion might play a role in inflammatory response. According to our immunohistochemical study, expression of melatonin could be detected in human oral mucosa. In addition, increased levels of melatonin were observed in inflamed oral mucosa of OLP patients. We hypothesize that chronic inflammation possibly induces the local biosynthesis of melatonin in inflamed oral mucosa. We also speculate that melatonin in oral mucosa may play a cytoprotective role through its anti-oxidative and anti-inflammatory properties. Moreover, melatonin may play an immunomodulatory role in relation to pathogenesis of OLP. Our hypothesis provides a new implication for upcoming research on the connection between circadian neuroendocrine network and immune response in oral mucosal compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters

    International Nuclear Information System (INIS)

    Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A.

    1996-01-01

    The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs

  1. Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A. [Southern Illinois Univ., Carbondale, IL (United States)

    1996-12-31

    The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs.

  2. Pharmacokinetics of Melatonin

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob

    2016-01-01

    Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of ...

  3. Relationship between plasma and salivary melatonin and cortisol investigated by LC-MS/MS.

    Science.gov (United States)

    van Faassen, Martijn; Bischoff, Rainer; Kema, Ido P

    2017-08-28

    Disturbance of the circadian rhythm has been associated with disease states, such as metabolic disorders, depression and cancer. Quantification of the circadian markers such as melatonin and cortisol critically depend on reliable and reproducible analytical methods. Previously, melatonin and cortisol were primarily analyzed separately, mainly using immunoassays. Here we describe the validation and application of a high-throughput liquid chromatography in combination with mass spectrometry (LC-MS/MS) method for the combined analysis of melatonin and cortisol in plasma and saliva. The LC-MS/MS method was validated according to international validation guidelines. We used this method to analyze total plasma, free plasma (as obtained by equilibrium dialysis) and saliva melatonin and cortisol in healthy adults. Validation results for plasma and saliva melatonin and cortisol were well within the international validation criteria. We observed no difference between saliva collected by passive drooling or Salivette. Moreover, we noted a significant difference in saliva vs. free plasma melatonin. We observed on average 36% (95% CI: 4%-60%) higher salivary melatonin levels in comparison to free plasma melatonin, suggestive of local production of melatonin in the salivary glands. The novel outcome of this study is probably due to the high precision of our LC-MS/MS assay. These outcomes illustrate the added value of accurate and sensitive mass spectrometry based methods for the quantification of neuroendocrine biomarkers.

  4. Validation of a direct radioimmunoassay of melatonin in the blue fox

    International Nuclear Information System (INIS)

    Forsberg, M.; Madej, A.

    1987-01-01

    A direct radioimmunoassay procedure for the determination of melatonin in the blood of blue fox has been validated and applied. The assay required 50 μl of sample and standard, 100 μl of antiserum and 100 μl of ( 3 H)melatonin. After overnight incubation at 4 deg. C the antibody bound melatonin was separated from the free hormone with dextran-coated charcoal. Following centrifugation the antibody bound ( 3 H)melatonin was determined in a beta scintillation counter. The antiserum bound 30-35 % of the ( 3 H)melatonin at a final dilution of 1:36000. The non specific binding represented less than 5 % of the total radioactivity in all assays. The lowest detectable amount of melatonin was 2.6 fmol/tube, corresponding to 52.5 pmol/l. The inter-assay coefficient of variation at 178 and 510 pmol/l was 15.6 and 8.8 %, respectively. The precision profile, calculated from a 10-replicate standard curve, showed that the coefficient of variation decreased from 43 % at 84 pmol/l to 15 % at 336 pmol/l, and remainded at or below 10 % for concentrations exceeding 670 pmol/l. Plasma was collected from 2 male blue foxes at about hourly intervals during a 24 h period in September and assayed for melatonin. Maximum (421 pmol/l) and minimum (97 pmol/l) concentrations of the hormone were inversely related to light intensity. (author)

  5. Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury

    Science.gov (United States)

    Li, Ji-Guo; Lin, Jia-Ji; Wang, Zhao-Ling; Cai, Wen-Ke; Wang, Pei-Na; Jia, Qian; Zhang, An-Sheng; Wu, Gao-Yi; Zhu, Guo-Xiong; Ni, Long-Xing

    2015-01-01

    Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1β, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1β in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1β and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that

  6. Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

    Science.gov (United States)

    Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

    2013-06-01

    Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p melatonin were less than those without melatonin treatment (p melatonin could mitigate CV after experimental SAH.

  7. Iatrogenic nocturnal eneuresis- an overlooked side effect of anti histamines?

    Directory of Open Access Journals (Sweden)

    D Italiano

    2015-01-01

    Full Text Available Nocturnal enuresis is a common disorder in childhood, but its pathophysiological mechanisms have not been fully elucidated. Iatrogenic nocturnal enuresis has been described following treatment with several psychotropic medications. Herein, we describe a 6-year-old child who experienced nocturnal enuresis during treatment with the antihistamine cetirizine. Drug rechallenge was positive. Several neurotransmitters are implicated in the pathogenesis of nocturnal enuresis, including noradrenaline, serotonin and dopamine. Antihistamine treatment may provoke functional imbalance of these pathways resulting in incontinence.

  8. Effects of melatonin and prolactin in reproduction: review of literature

    OpenAIRE

    Tenorio, Fernanda das Chagas Angelo Mendes; Simões, Manuel de Jesus; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

    2015-01-01

    Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a ...

  9. Exogenous melatonin improves Malus resistance to Marssonina apple blotch.

    Science.gov (United States)

    Yin, Lihua; Wang, Ping; Li, Mingjun; Ke, Xiwang; Li, Cuiying; Liang, Dong; Wu, Shan; Ma, Xinli; Li, Chao; Zou, Yangjun; Ma, Fengwang

    2013-05-01

    We examined whether exogenously applied melatonin could improve resistance to Marssonina apple blotch (Diplocarpon mali) by apple [Malus prunifolia (Willd.) Borkh. cv. Donghongguo]. This serious disease leads to premature defoliation in the main regions of apple production. When plants were pretreated with melatonin, resistance was increased in the leaves. We investigated the potential roles for melatonin in modulating levels of hydrogen peroxide (H2O2), as well the activities of antioxidant enzymes and pathogenesis-related proteins during these plant-pathogen interactions. Pretreatment enabled plants to maintain intracellular H2O2 concentrations at steady-state levels and enhance the activities of plant defence-related enzymes, possibly improving disease resistance. Because melatonin is safe and beneficial to animals and humans, exogenous pretreatment might represent a promising cultivation strategy to protect plants against this pathogen infection. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. Effect of melatonin supplementation on pregnancy outcome in Wistar-Kyoto and Sprague-Dawley rats.

    Science.gov (United States)

    Singh, Harbindar Jeet; Saleh, Hisham Ibrahim; Gupalo, Sergey; Omar, Effat

    2013-04-25

    Although melatonin supplementation is known to influence numerous physiological functions, little is however known of its effects on pregnancy outcome. This study investigated the effects of melatonin supplementation on pregnancy outcome in Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats aged 12-13 weeks. Upon confirmation of proestrus, each female rat was housed overnight with a male of the same strain. On the next morning, following confirmation of mating (vaginal smear), WKY female rats were isolated into individual metabolic cages and given 0, 25, 50 or 100 mg/kg per day of melatonin in drinking water from day 1 of pregnancy to day 21 postpartum. SD females were given 0 or 100 mg/kg per day of melatonin. Maternal weight, duration of pregnancy, litter size, birth weight and body weight of pups up to day 42, and pup mortality were recorded. Data were analyzed using ANOVA for repeated measures. Compared to controls, maternal weight gain during pregnancy was significantly lower in melatonin-supplemented dams (P melatonin-supplemented dams (P melatonin (P melatonin was significantly lower than controls (P melatonin respectively, and all pup deaths occurred after day 21 of weaning. The results suggest that melatonin supplementation during antenatal and postpartum period appears to adversely affect litter size, pup growth and mortality in WKY and SD rats. The precise mechanism causing the death is not clear.

  11. Melatonin potentiates glycine currents through a PLC/PKC signalling pathway in rat retinal ganglion cells.

    Science.gov (United States)

    Zhao, Wen-Jie; Zhang, Min; Miao, Yanying; Yang, Xiong-Li; Wang, Zhongfeng

    2010-07-15

    In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin-induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT(2) receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT(2) receptor antagonist 4-P-PDOT. The melatonin effect was blocked by intracellular dialysis of GDP-beta-S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)-PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin-induced potentiation. The melatonin effect persisted when [Ca(2+)](i) was chelated by BAPTA, and melatonin induced no increase in [Ca(2+)](i). Neither cAMP-PKA nor cGMP-PKG signalling pathways seemed to be involved because 8-Br-cAMP or 8-Br-cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H-89 and the PKG inhibitor KT5823 did not block the melatonin-induced potentiation. In consequence, a distinct PC-PLC/PKC signalling pathway, following the activation of G(i/o)-coupled MT(2) receptors, is most likely responsible for the melatonin-induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light-evoked glycine receptor-mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner

  12. Alterations in the circadian rhythm of salivary melatonin begin during middle-age

    NARCIS (Netherlands)

    Zhou, Jiang-Ning; Liu, Rong-Yu; van Heerikhuize, Joop; Hofman, Michel A.; Swaab, Dick F.

    2003-01-01

    To investigate whether free melatonin may be better suited to reveal age-related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take

  13. Rapid voltammetric monitoring of melatonin in the presence of tablet excipients

    International Nuclear Information System (INIS)

    Ball, Andrew T.; Patel, Bhavik Anil

    2012-01-01

    Melatonin is an important neurohormonal chemical that is responsible for regulating sleep. Melatonin dietary supplements are available and utilised to counteract the effects of jet-lag or to aid sleep. Voltammetric detection with a boron-doped diamond electrode was utilised for the rapid monitoring of individual melatonin tablets. Melatonin was oxidised at a potential of +0.8 V vs. Ag|AgCl. Voltammetric measurements were carried out without the need of excessive sample preparation steps such as filtration. However dicalcium phosphate and carboxymethyl cellulose were shown to alter the electrochemical response. Calibration responses were linear over a concentration of 2–4 mg/25 ml of melatonin and a limit of detection of 0.06 mg/25 ml was observed. Volammetric recordings were only stable for one measurement, but the electrode surface could be replenished following a single wipe of an ethanol soaked lens cloth. This new assay was capable of analysing individual melatonin tablets within a total analysis time of 2.5 min. Overall this approach provides the basis for rapid electrochemical monitoring of pharmaceutical and dietary tablets without the need for extensive sample preparation.

  14. Melatonin reverses type 2 diabetes-induced cognitive deficits via ...

    African Journals Online (AJOL)

    Purpose: To evaluate the protective effect of melatonin on diabetes-induced cognitive dysfunction. Methods: Rats ... suggests that melatonin may be useful for the management of cognitive dysfunction in patients suffering ... as amyotrophic lateral sclerosis, Alzheimer's disease ..... with the inhibitory kappa beta (Iκβ) family.

  15. Studies on circadian rhythm disturbances and melatonin in delirium

    NARCIS (Netherlands)

    de Jonghe, A.-M.

    2014-01-01

    The circadian sleep/wake rhythm disturbances that are seen in delirium and the role of melatonin supplementation provide a new angle in delirium research. More research is needed to determine the role of melatonin in the pathophysiological mechanisms of delirium and to determine whether the

  16. Reactions of melatonin with radicals in deoxygenated aqueous solution

    International Nuclear Information System (INIS)

    Stasica, P.; Ulanski, P.; Rosiak, J.M.

    1998-01-01

    Reactions of melatonin (N-acetyl-5-methoxytryptamine) with radiolytically generated radicals were studied. Reaction of melatonin with OH radicals is diffusion-controlled (k=1.2 x 10 10 dm 3 mol -1 x s -1 ), the main (but not the only one) intermediate being the indolyl-type radical, while the rate constant for the reaction with hydrated electrons is k=4.3 x 10 8 dm 3 x mol -1 x s -1 . Melatonin is capable of scavenging tert-butanol radicals, while its reactivity towards polymer radicals of poly(acrylic acid) and poly(vinyl pyrrolidone) is very low. (author)

  17. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial.

    Science.gov (United States)

    Riemersma-van der Lek, Rixt F; Swaab, Dick F; Twisk, Jos; Hol, Elly M; Hoogendijk, Witte J G; Van Someren, Eus J W

    2008-06-11

    also increased withdrawn behavior by 1.02 points (95% CI, 0.18-1.86) on the Multi Observational Scale for Elderly Subjects scale, although this effect was not seen if given in combination with light. Combined treatment also attenuated aggressive behavior by 3.9 points (95% CI, 0.88-6.92) on the Cohen-Mansfield Agitation Index or 9%, increased sleep efficiency by 3.5% (95% CI, 0.8%-6.1%), and improved nocturnal restlessness by 1.00 minute per hour each year (95% CI, 0.26-1.78) or 9% (treatment x time effect). Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia. To counteract the adverse effect of melatonin on mood, it is recommended only in combination with light. controlled-trials.com/isrctn Identifier: ISRCTN93133646.

  18. Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2017-12-01

    Full Text Available Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice, when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life. We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE, a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.

  19. Topical Melatonin for Treatment of Androgenetic Alopecia

    OpenAIRE

    Fischer, Tobias W; Tr?eb, Ralph M; H?nggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-01-01

    Background: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. Materials and Methods: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardise...

  20. Melatonin synthesis under calcium constraint in gilthead sea bream (Sparus auratus L.)

    NARCIS (Netherlands)

    Abbink, W.; Kulczkowska, E.; Kalamarz, H.; Guerreiro, P.M.G.; Flik, G.

    2008-01-01

    Brain or blood plasma melatonin was analysed as a measure for pineal melatonin production in sea bream. Access to calcium was limited by diluting the seawater to 2.5‰ and removing calcium from the diet or by prolonged feeding of vitamin D-deficient diet. Interactions/relations between melatonin and

  1. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo

    OpenAIRE

    Itani, Nozomi; Skeffington, Katie L.; Beck, Christian; Niu, Youguo; Giussani, Dino A.

    2015-01-01

    Abstract There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment comm...

  2. Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes.

    Science.gov (United States)

    Vlachou, Marilena; Papamichael, Marianna; Siamidi, Angeliki; Fragouli, Irene; Afroudakis, Pandelis A; Kompogennitaki, Rodanthi; Dotsikas, Yannis

    2017-07-28

    A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

  3. Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens

    International Nuclear Information System (INIS)

    Rollag, M.D.; Niswender, G.D.

    1976-01-01

    A specific and sensitive double-antibody radioimmunoassay for melatonin (N-acetyl-5-methoxytryptamine) was developed. The least detectable concentration of melatonin standard was 10 pmolar (2.3 pg/tube) with 50 percent inhibition resulting when the concentration was 100 pmolar (23 pg/tube). Inhibition curves obtained with increasing quantities of melatonin or increasing quantities of chloroform extracts of ovine sera were parallel. Concentrations of melatonin could be accurately determined when 31 to 1000 pg were added to 1 ml ovine serum. Serum samples with melatonin concentrations of 1000 pg/ml, 500 pg/ml and 75 pg/ml had intra-assay coefficients of variation of 9.1 percent, 8.6 percent, and 17.4 percent, respectively. The respective inter-assay coefficients of variation were 22.7 percent, 18.1 percent, and 37.1 percent. Ewes exposed to a 12 h light:12 h dark lighting regimen demonstrated a circadian rhythm in serum concentrations of melatonin. Concentrations ranged from 10 to 30 pg/ml during periods of light to 100 to 300 pg/ml during periods of dark. During exposure to continuous light, the circadian rhythm was abolished and concentrations of melatonin were maintained at 10 to 50 pg/ml. When exposed to conditions of continuous dark the circadian rhythm persisted. A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light. Concentrations returned to peak levels when the lights were turned off 3.5 h later

  4. Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science.

    Science.gov (United States)

    Tan, Dun-Xian; Hardeland, Rudiger; Manchester, Lucien C; Korkmaz, Ahmet; Ma, Shuran; Rosales-Corral, Sergio; Reiter, Russel J

    2012-01-01

    The presence of melatonin in plants is universal. Evidence has confirmed that a major portion of the melatonin is synthesized by plants themselves even though a homologue of the classic arylalkylamine N-acetyltransferase (AANAT) has not been identified as yet in plants. Thus, the serotonin N-acetylating enzyme in plants may differ greatly from the animal AANAT with regard to sequence and structure. This would imply multiple evolutionary origins of enzymes with these catalytic properties. A primary function of melatonin in plants is to serve as the first line of defence against internal and environmental oxidative stressors. The much higher melatonin levels in plants compared with those found in animals are thought to be a compensatory response by plants which lack means of mobility, unlike animals, as a means of coping with harsh environments. Importantly, remarkably high melatonin concentrations have been measured in popular beverages (coffee, tea, wine, and beer) and crops (corn, rice, wheat, barley, and oats). Billions of people worldwide consume these products daily. The beneficial effects of melatonin on human health derived from the consumption of these products must be considered. Evidence also indicates that melatonin has an ability to increase the production of crops. The mechanisms may involve the roles of melatonin in preservation of chlorophyll, promotion of photosynthesis, and stimulation of root development. Transgenic plants with enhanced melatonin content could probably lead to breakthroughs to increase crop production in agriculture and to improve the general health of humans.

  5. Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

    OpenAIRE

    Reiter, Russel J.; Rosales-Corral, Sergio A.; Manchester, Lucien C.; Tan, Dun-Xian

    2013-01-01

    Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fer...

  6. Desmopressin is an effective treatment for mixed nocturia with nocturnal polyuria and decreased nocturnal bladder capacity.

    Science.gov (United States)

    Lee, Hye Won; Choo, Myung-Soo; Lee, Jeong Gu; Park, Choal Hee; Paick, Jae-Seung; Lee, Jeong Zoo; Han, Deok Hyun; Park, Won Hee; Lee, Kyu-Sung

    2010-12-01

    To investigate the efficacy and safety of desmopressin in patients with mixed nocturia, Patients aged ≥ 18 yr with mixed nocturia (≥ 2 voids/night and a nocturnal polyuria index [NPi] >33% and a nocturnal bladder capacity index [NBCi] >1) were recruited. The optimum dose of oral desmopressin was determined during a 3-week dose-titration period and the determined dose was maintained for 4 weeks. The efficacy was assessed by the frequency-volume charts and the sleep questionnaire. The primary endpoint was the proportion of patients with a 50% or greater reduction in the number of nocturnal voids (NV) compared with baseline. Among 103 patients enrolled, 94 (79 men and 15 women) were included in the analysis. The proportion of patients with a 50% or greater reduction in NV was 68 (72%). The mean number of NV decreased significantly (3.20 to 1.34) and the mean nocturnal urine volume, nocturia index, NPi, and NBCi decreased significantly. The mean duration of sleep until the first NV was prolonged from 118.4 ± 44.1 to 220.3 ± 90.7 min (P<0.001). The overall impression of patients about their quality of sleep improved. Adverse events occurred in 6 patients, including one asymptomatic hyponatremia. Desmopressin is an effective and well-tolerated treatment for mixed nocturia.

  7. Melatonin Is Involved in Regulation of Bermudagrass Growth and Development and Response to Low K+ Stress

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2017-11-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine plays critical roles in plant growth and development and during the response to multiple abiotic stresses. However, the roles of melatonin in plant response to K+ deficiency remain largely unknown. In the present study, we observed that the endogenous melatonin contents in bermudagrass were remarkably increased by low K+ (LK treatment, suggesting that melatonin was involved in bermudagrass response to LK stress. Further phenotype analysis revealed that exogenous melatonin application conferred Bermudagrass enhanced tolerance to LK stress. Interestingly, exogenous melatonin application also promoted bermudagrass growth and development at normal condition. Furthermore, the K+ contents measurement revealed that melatonin-treated plants accumulated more K+ in both shoot (under both control and LK condition and root tissues (under LK condition compared with those of melatonin non-treated plants. Expression analysis indicated that the transcripts of K+ transport genes were significantly induced by exogenous melatonin treatment in bermudagrass under both control and LK stress conditions, especially under a combined treatment of LK stress and melatonin, which may increase accumulation of K+ content profoundly under LK stress and thereby contributed to the LK-tolerant phenotype. In addition, we investigated the role of melatonin in the regulation of photosystem II (PSII activities under LK stress. The chlorophyll fluorescence transient (OJIP curves were obviously higher in plants grown in LK with melatonin (LK+Mel than those of plants grown in LK medium without melatonin application for 1 or 2 weeks, suggesting that melatonin plays important roles in PSII against LK stress. After a combined treatment of LK stress and melatonin, the values for performance indexes (PIABS, PITotal, and PICS, flux ratios (φP0, ΨE0, and φE0 and specific energy fluxes (ETO/RC were significantly improved compared with those of LK

  8. Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in Apple Leaf

    Directory of Open Access Journals (Sweden)

    Zhiwei Wei

    2018-01-01

    Full Text Available Oxidative stress is a major source of damage of plants exposed to adverse environments. We examined the effect of exogenous melatonin (MT in limiting of oxidative stress caused by methyl viologen (MV; paraquatin in apple leaves (Malus domestica Borkh.. When detached leaves were pre-treated with melatonin, their level of stress tolerance increased. Under MV treatment, melatonin effectively alleviated the decrease in chlorophyll concentrations and maximum potential Photosystem II efficiency while also mitigating membrane damage and lipid peroxidation when compared with control leaves that were sprayed only with water prior to the stress experiment. The melatonin-treated leaves also showed higher activities and transcripts of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, the expression of genes for those enzymes was upregulated. Melatonin-synthesis genes MdTDC1, MdT5H4, MdAANAT2, and MdASMT1 were also upregulated under oxidative stress in leaves but that expression was suppressed in response to 1 mM melatonin pretreatment during the MV treatments. Therefore, we conclude that exogenous melatonin mitigates the detrimental effects of oxidative stress, perhaps by slowing the decline in chlorophyll concentrations, moderating membrane damage and lipid peroxidation, increasing the activities of antioxidant enzymes, and changing the expression of genes for melatonin synthesis.

  9. Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

    Science.gov (United States)

    Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang

    2017-10-01

    Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Potential of melatonin for prevention of age-related macular degeneration: experimental study].

    Science.gov (United States)

    Stefanova, N A; Zhdankina, A A; Fursova, A Zh; Kolosova, N G

    2013-01-01

    Decline with age of the content of melatonin is considered as one of the leading mechanisms of aging and development of associated diseases, including age-related macular degeneration (AMD)--the disease, which becomes the most common cause of blindness and acuity of vision deterioration in elderly. The prospects of the use of melatonin in the prevention of AMD is being actively discussed, but as a rule on the basis of the results of the experiments on cells in retinal pigment epithelium (RPE). We showed previously that the senescence-accelerated OXYS rat is an adequate animal model of AMD, already used for identifying the relevant therapeutic targets. Here we have investigated the effect of Melatonin (Melaksen, 0,004 mg per kg--a dose equivalent to the recommended one for people) on the development of retinopathy similar to AMD in OXYS rats. Ophthalmoscopic examinations show that Melatonin supplementation decreased the incidence and severity of retinopathy and improved some (but not all) histological abnormalities associated with retinopathy. Thus, melatonin prevented the structural and functional changes in RPE cells, reduced the severity of microcirculatory disorders. Importantly, Melatonin prevented destruction of neurosensory cells, associative and gangliolar neurons in the retina. Taken together, our data suggest the therapeutic potential of Melatonin for treatment and prevention of AMD.

  11. Current knowledge on the melatonin system in teleost fish.

    Science.gov (United States)

    Falcón, J; Migaud, H; Muñoz-Cueto, J A; Carrillo, M

    2010-02-01

    Melatonin is a much conserved feature in vertebrates that plays a central role in the entrainment of daily and annual physiological rhythms. Investigations aiming at understanding how melatonin mediates the effects of photoperiod on crucial functions and behaviors have been very active in the last decades, particularly in mammals. In fish a clear-cut picture is still missing. Here we review the available data on (i) the sites of melatonin production in fish, (ii) the mechanisms that control its daily and annual rhythms of production and (iii) the characterization of its different receptor subtypes, their location and regulation. The in vivo and in vitro data on melatonin effects on crucial neuroendocrine regulations, including reproduction, growth, feeding and behavioral responses, are also reviewed. Finally we discuss how manipulation of the photic cues impact on fish circannual clock and annual cycle of reproduction, and how this can be used for aquaculture purposes. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus.

    Science.gov (United States)

    Kor, Yilmaz; Geyikli, Iclal; Keskin, Mehmet; Akan, Muslum

    2014-07-01

    Melatonin is an indolamine hormone, synthesized from tryptophan in the pineal gland primarily. Melatonin exerts both antioxidative and immunoregulatory roles but little is known about melatonin secretion in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to measure serum melatonin levels in patients with T1DM and investigates their relationship with type 1 diabetes mellitus. Forty children and adolescents with T1DM (18 boys and 22 girls) and 30 healthy control subjects (17 boys and 13 girls) participated in the study. All patients followed in Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine and also control subjects had no hypertension, obesity, hyperlipidemia, anemia, and infection. Blood samples were collected during routine analysis, after overnight fasting. Serum melatonin levels were analyzed with ELISA. There were no statistically significant differences related with age, sex, BMI distribution between diabetic group and control group. Mean diabetic duration was 2.89 ± 2.69 years. The variables were in the equation. Mean melatonin level in diabetic group was 6.75 ± 3.52 pg/ml and mean melatonin level in control group was 11.51 ± 4.74 pg/ml. Melatonin levels were significantly lower in diabetic group compared to controls (P 1). Melatonin was associated with type 1 diabetes mellitus significantly. Because of the varied roles of melatonin in human metabolic rhythms, these results suggest a role of melatonin in maintaining normal rhythmicity. Melatonin may play role in preventing process of inflammation and oxidative stress.

  13. Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yilmaz Kor

    2014-01-01

    Full Text Available Objective: Melatonin is an indolamine hormone, synthesized from tryptophan in the pineal gland primarily. Melatonin exerts both antioxidative and immunoregulatory roles but little is known about melatonin secretion in patients with type 1 diabetes mellitus (T1DM. The aim of this study was to measure serum melatonin levels in patients with T1DM and investigates their relationship with type 1 diabetes mellitus. Materials and Methods: Forty children and adolescents with T1DM (18 boys and 22 girls and 30 healthy control subjects (17 boys and 13 girls participated in the study. All patients followed in Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine and also control subjects had no hypertension, obesity, hyperlipidemia, anemia, and infection. Blood samples were collected during routine analysis, after overnight fasting. Serum melatonin levels were analyzed with ELISA. Results: There were no statistically significant differences related with age, sex, BMI distribution between diabetic group and control group. Mean diabetic duration was 2.89 ± 2.69 years. The variables were in the equation. Mean melatonin level in diabetic group was 6.75 ± 3.52 pg/ml and mean melatonin level in control group was 11.51 ± 4.74 pg/ml. Melatonin levels were significantly lower in diabetic group compared to controls (P < 0.01. Conclusions: Melatonin was associated with type 1 diabetes mellitus significantly. Because of the varied roles of melatonin in human metabolic rhythms, these results suggest a role of melatonin in maintaining normal rhythmicity. Melatonin may play role in preventing process of inflammation and oxidative stress.

  14. Nocturnal enuresis in india: Are we diagnosing and managing correctly?

    Directory of Open Access Journals (Sweden)

    N M Reddy

    2017-01-01

    Full Text Available Nocturnal enuresis is a common problem affecting school-aged children worldwide. Although it has significant impact on child's psychology, it is always under-recognized in India and considered as a condition which will outgrow with advancing age. Nocturnal enuresis classified as primary or secondary and monosymptomatic or nonmonosymptomatic. Factors that cause enuresis include genetic factors, bladder dysfunction, psychological factors, and inappropriate antidiuretic hormone secretion, leading to nocturnal polyuria. Diagnosis consists of detailed medical history, clinical examination, frequency-volume charts, and appropriate investigations. The frequency-volume chart or voiding diary helps in establishing diagnosis and tailoring therapy. The first step in treating nocturnal enuresis is to counsel the parents and the affected child about the condition and reassure them that it can be cured. One of the effective strategies to manage enuresis is alarm therapy, but currently, it is not easily available in India. Desmopressin has been used in the treatment of nocturnal enuresis for close to 50 years. It provides an effective and safe option for the management of nocturnal enuresis. This review covers the diagnosis and management of nocturnal enuresis and introduces the concept of “bedwetting clinics” in India, which should help clinicians in the thorough investigation of bedwetting cases.

  15. Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis.

    Science.gov (United States)

    Dossche, L; Raes, A; Hoebeke, P; De Bruyne, P; Vande Walle, J

    2016-01-01

    Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Children's Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

    Directory of Open Access Journals (Sweden)

    Oliver eRawashdeh

    2012-03-01

    Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

  17. Effect of topical application of melatonin cream 12.5% on cognitive parameters

    DEFF Research Database (Denmark)

    Scheuer, Cecilie; Pommergaard, Hans-Christian; Rosenberg, Jacob

    2016-01-01

    BACKGROUND: Skin cancer is an increasing problem in modern dermatology. Earlier studies have shown protective effects against ultraviolet radiation (UVR)-induced skin damage by topical treatment with melatonin. However, the potential sedative effects of full body topical application of melatonin...... have never been investigated. Objectives The aim of this study was to assess the degree of cognitive dysfunction when using melatonin cream as full body topical application. METHODS: In a randomized, placebo-controlled, double-blind crossover study in healthy volunteers, the degree of cognitive...... dysfunction when using cream containing 12.5% melatonin as full body application was assessed. A group of ten volunteers had melatonin cream 12.5% applied on 80% of their body surface area, and degree of cognitive dysfunction was assessed using a test battery consisting of Karolinska sleepiness scale (KSS...

  18. Involvement of the nitric oxide in melatonin-mediated protection against injury.

    Science.gov (United States)

    Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

    2018-05-01

    Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

    Science.gov (United States)

    Jang, Hoon; Hong, Kwonho; Choi, Youngsok

    2017-06-07

    Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients.

  20. Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

    Directory of Open Access Journals (Sweden)

    Lucia Marseglia

    2015-01-01

    Full Text Available Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.

  1. Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

    Directory of Open Access Journals (Sweden)

    Savvidou Olga D

    2007-04-01

    Full Text Available Abstract Melatonin "the light of night" is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS. Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed.

  2. Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Dubbels, R.; Klenke, E.; Schnakenberg, E.; Ehlers, C.; Schloot, W.; Reiter, R.J.; Goebel, A.; Schiware, H.W.

    1995-01-01

    Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage. (au) 30 refs

  3. High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

    Science.gov (United States)

    Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

    2017-05-05

    N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

  4. Night work, light exposure and melatonin on work days and days off.

    Science.gov (United States)

    Daugaard, Stine; Garde, Anne Helene; Bonde, Jens Peter Ellekilde; Christoffersen, Jens; Hansen, Äse Marie; Markvart, Jakob; Schlünssen, Vivi; Skene, Debra J; Vistisen, Helene Tilma; Kolstad, Henrik A

    2017-01-01

    We aimed to examine the effects of night work on salivary melatonin concentration during and subsequent to night work and the mediating role of light. We included 254 day workers and 87 night workers who were followed during 322 work days and 301 days off work. Each day was defined as the 24 hour period starting from the beginning of a night shift or from waking in the mornings with day work and days off. Light levels were recorded and synchronized with diary information (start and end of sleep and work). On average, participants provided four saliva samples per day, and these were analyzed for melatonin concentration by liquid chromatography tandem mass spectrometry (LC-MS/MS). Differences between day and night workers on work days and days off were assessed with multilevel regression models with melatonin concentration as the primary outcome. All models were stratified or adjusted by time of day. For light exposure, we estimated the total, direct and indirect effects of night work on melatonin concentrations obtaining 95% confidence intervals through bootstrapping. On work days, night workers showed 15% lower salivary melatonin concentrations compared with day workers (-15.0%; 95% CI: -31.4%; 5.2%). During the night, light exposure mediated a melatonin suppression of approximately 6% (-5.9%, 95% CI: -10.2%; -1.5%). No mediating effect of light was seen during the day time. On days off, we observed no difference in melatonin concentrations between day and night workers. These findings are in accordance with a transient and partly light-mediated effect of night work on melatonin production.

  5. Progressive decrease of melatonin production over consecutive days of simulated night work.

    Science.gov (United States)

    Dumont, Marie; Paquet, Jean

    2014-12-01

    Decreased melatonin production, due to nighttime exposure to light, has been proposed as one of the physiological mechanisms increasing cancer risk in night workers. However, few studies measured melatonin production in night workers, and most of these studies did not measure melatonin over 24 h. One study compared total melatonin production between day and night shifts in rotating night workers and did not find significant differences. However, without baseline measures, it was not possible to exclude that melatonin production was reduced during both day and night work. Here, we used data collected in a simulation study of night work to determine the effect of night work on both nighttime and 24-h melatonin production, during three consecutive days of simulated night work. Thirty-eight healthy subjects (15 men, 23 women; 26.6 ± 4.2 years) participated in a 6-d laboratory study. Circadian phase assessments were made with salivary dim light melatonin onset (DLMO) on the first and last days. Simulated day work (09:00-17:00 h) occurred on the second day, followed by three consecutive days of simulated night work (00:00-08:00 h). Light intensity at eye level was set at 50 lux during both simulated day and night work. The subjects were divided into three matched groups exposed to specific daytime light profiles that produced various degrees of circadian phase delays and phase advances. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s). For the entire protocol, urine was collected every 2 h, except for the sleep episodes when the interval was 8 h. The aMT6s concentration in each sample was multiplied by the urine volume and then added to obtain total aMT6s excretion during nighttime (00:00-08:00 h) and during each 24-h day (00:00-00:00 h). The results showed that melatonin production progressively decreased over consecutive days of simulated night work, both during nighttime and over the 24 h. This

  6. Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Banerjee, Arnab; Meenakumari, K J; Udin, S; Krishna, A

    2009-12-01

    The aim of the present study was to evaluate the seasonal variation in serum melatonin levels and their relationship to the changes in the serum progesterone level, ovarian steroidogenesis, and embryonic development during two successive pregnancies of Cynopterus sphinx. Circulating melatonin concentrations showed two peaks; one coincided with the period of low progesterone synthesis and delayed embryonic development, whereas the second peak coincided with regressing corpus luteum. This finding suggests that increased serum melatonin level during November-December may be responsible for delayed embryonic development by suppressing progesterone synthesis. The study showed increased melatonin receptors (MTNR1A and MTNR1B) in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed that a high dose of melatonin suppressed progesterone synthesis, whereas a lower dose of melatonin increased progesterone synthesis by the ovary. The effects of melatonin on ovarian steroidogenesis are mediated through changes in the expression of peripheral-type benzodiazepine receptor, P450 side chain cleavage enzyme, and LH receptor proteins. This study further showed a suppressive impact of melatonin on the progesterone receptor (PGR) in the utero-embryonic unit; this effect might contribute to delayed embryonic development in C. sphinx. The results of the present study thus suggest that a high circulating melatonin level has a dual contribution in retarding embryonic development in C. sphinx by impairing progesterone synthesis as well as by inhibiting progesterone action by reducing expression of PGR in the utero-embryonic unit.

  7. Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

    Science.gov (United States)

    De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

    2007-12-01

    Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

  8. Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells

    Science.gov (United States)

    Loureiro, Rute; Magalhães-Novais, Silvia; Mesquita, Katia A.; Baldeiras, Ines; Sousa, Isabel S.; Tavares, Ludgero C.; Barbosa, Ines A.; Oliveira, Paulo J.; Vega-Naredo, Ignacio

    2015-01-01

    Although melatonin oncostatic and cytotoxic effects have been described in different types of cancer cells, the specific mechanisms leading to its antitumoral effects and their metabolic context specificity are still not completely understood. Here, we evaluated the effects of melatonin in P19 embryonal carcinoma stem cells (CSCs) and in their differentiated counterparts, cultured in either high glucose medium or in a galactose (glucose-free) medium which leads to glycolytic suppression and increased mitochondrial metabolism. We found that highly glycolytic P19 CSCs were less susceptible to melatonin antitumoral effects while cell populations relying on oxidative metabolism for ATP production were more affected. The observed antiproliferative action of melatonin was associated with an arrest at S-phase, decreased oxygen consumption, down-regulation of BCL-2 expression and an increase in oxidative stress culminating with caspase-3-independent cell death. Interestingly, the combined treatment of melatonin and dichloroacetate had a synergistic effect in cells grown in the galactose medium and resulted in an inhibitory effect in the highly resistant P19 CSCs. Melatonin appears to exert its antiproliferative activity in P19 carcinoma cells through a mitochondrially-mediated action which in turn allows the amplification of the effects of dichloroacetate, even in cells with a more glycolytic phenotype. PMID:26025920

  9. Ghrelin and melatonin as biomarkers in patients with giardiasis

    Directory of Open Access Journals (Sweden)

    Saleem Khteer Al-Hadraawy

    2016-05-01

    Full Text Available Giardia is the most frequently reported intestinal parasite worldwide. The aim of this study was to investigate the ghrelin, melatonin, glucose and cholesterol concentration in male patients infected with Giardia lamblia. We enrolled 66 patients with Giardiasis and the control groups consisted of healthy subjects (n = 30. The results demonstrated that there was a significant decrease (P < 0.05 in ghrelin levels, while the melatonin, glucose and cholesterol levels were significantly increased (P < 0.05 in giardiasis patients as compared to the healthy group. The obtained results suggest that ghrelin and melatonin could serve as biomarkers in patients infected with G. lamblia.

  10. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  11. Antioxidative effects of melatonin on kinetics, microscopic and oxidative parameters of cryopreserved bull spermatozoa.

    Science.gov (United States)

    Ashrafi, Iraj; Kohram, Hamid; Ardabili, Farhad Farrokhi

    2013-06-01

    Reactive oxygen species generated during the freeze-thawing process may reduce sperm quality. This study evaluates the effects of melatonin supplementation as an antioxidant in the semen extender on post-thaw parameters of bull spermatozoa. Melatonin was added to the citrate-egg yolk extender to yield six different final concentrations: 0, 0.1, 1, 2, 3 and 4mM. Ejaculates were collected from six proven Holstein bulls. Semen was diluted in the extender packaged in straws, which was frozen with liquid nitrogen. The semen extender supplemented with various doses of melatonin increased (peffective concentration of melatonin in microscopic evaluations of the bull sperm freezing extender was 2mM. The highest (pconcentration of melatonin in the semen extender and the highest activity of catalase (0.7±0.1) was obtained by 2mM melatonin. Four millimolar concentration of melatonin were reduced (pconcentration of melatonin in the semen extender improved the quality of post-thawed semen, which may associate with a reduction in lipid peroxidation as well as an increase in the total antioxidant capacity and antioxidant enzyme activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Loss of response to melatonin treatment is associated with slow melatonin metabolism

    NARCIS (Netherlands)

    Braam, W.J.; Geijlswijk, I.M. van; Keijzer, H.; Smits, M.G.; Didden, H.C.M.; Curfs, L.M.G.

    2010-01-01

    Background In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to

  13. Effects of melatonin and prolactin in reproduction: review of literature.

    Science.gov (United States)

    Tenorio, Fernanda das Chagas Angelo Mendes; Simões, Manuel de Jesus; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

    2015-01-01

    The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

  14. Effects of melatonin and prolactin in reproduction: review of literature

    Directory of Open Access Journals (Sweden)

    Fernanda das Chagas Angelo Mendes Tenorio

    2015-06-01

    Full Text Available Summary The pineal gland is responsible for producing a hormone called melatonin (MEL, and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

  15. Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

    Science.gov (United States)

    Fuentes-Broto, Lorena; Miana-Mena, Francisco J; Piedrafita, Eduardo; Berzosa, César; Martínez-Ballarín, Enrique; García-Gil, Francisco A; Reiter, Russel J; García, Joaquín J

    2010-08-01

    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 FeCl(3) 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. Published 2010 Wiley-Liss, Inc.

  16. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

    NARCIS (Netherlands)

    Geijlswijk, I.M. van; Heijden, K.B. van der; Egberts, A.C.G.; Korzilius, H.P.L.M.; Smits, M.G.

    2010-01-01

    Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and

  17. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT.

    NARCIS (Netherlands)

    van Geijlswijk, I.M.; van der Heijden, K.B.; Egberts, A.C.G.; Korzilius, H.P.; Smits, M.G.

    2010-01-01

    RATIONALE: Pharmacokinetics of melatonin in children might differ from that in adults. OBJECTIVES: This study aims to establish a dose-response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and

  18. Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Radogna, F.; Sestili, P.; Martinelli, C.; Paolillo, M.; Paternoster, L.; Albertini, M.C.; Accorsi, A.; Gualandi, G.; Ghibelli, L.

    2009-01-01

    We have shown that melatonin immediately and transiently stimulates intracellular free radical production on a set of leukocytes, possibly as a consequence of calmodulin binding. We show here that melatonin-induced ROS are produced by lipoxygenase (LOX), since they are prevented by a set of LOX inhibitors, and are accompanied by increase of the 5-LOX product 5-HETE. LOX activation is accompanied by strong liberation of AA; inhibition of Ca 2+ -independent, but not Ca 2+ -dependent, phospholipase A2 (PLA2), prevents both melatonin-induced arachidonic acid and ROS production, whereas LOX inhibition only prevents ROS, indicating that PLA2 is upstream with respect to LOX, as occurs in many signaling pathways. Chlorpromazine, an inhibitor of melatonin-calmodulin interaction, inhibits both ROS and arachidonic acid production, thus possibly placing calmodulin at the origin of a melatonin-induced pro-radical pathway. Interestingly, it is known that Ca 2+ -independent PLA2 binds to calmodulin: our results are compatible with PLA2 being liberated by melatonin from a steady-state calmodulin sequestration, thus initiating an arachidonate signal transduction. These results delineate a novel molecular pathway through which melatonin may participate to the inflammatory response.

  19. Eye shape and the nocturnal bottleneck of mammals.

    Science.gov (United States)

    Hall, Margaret I; Kamilar, Jason M; Kirk, E Christopher

    2012-12-22

    Most vertebrate groups exhibit eye shapes that vary predictably with activity pattern. Nocturnal vertebrates typically have large corneas relative to eye size as an adaptation for increased visual sensitivity. Conversely, diurnal vertebrates generally demonstrate smaller corneas relative to eye size as an adaptation for increased visual acuity. By contrast, several studies have concluded that many mammals exhibit typical nocturnal eye shapes, regardless of activity pattern. However, a recent study has argued that new statistical methods allow eye shape to accurately predict activity patterns of mammals, including cathemeral species (animals that are equally likely to be awake and active at any time of day or night). Here, we conduct a detailed analysis of eye shape and activity pattern in mammals, using a broad comparative sample of 266 species. We find that the eye shapes of cathemeral mammals completely overlap with nocturnal and diurnal species. Additionally, most diurnal and cathemeral mammals have eye shapes that are most similar to those of nocturnal birds and lizards. The only mammalian clade that diverges from this pattern is anthropoids, which have convergently evolved eye shapes similar to those of diurnal birds and lizards. Our results provide additional evidence for a nocturnal 'bottleneck' in the early evolution of crown mammals.

  20. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

    International Nuclear Information System (INIS)

    Ferreira, S.G.; Peliciari-Garcia, R.A.; Takahashi-Hyodo, S.A.; Rodrigues, A.C.; Amaral, F.G.; Berra, C.M.; Bordin, S.; Curi, R.; Cipolla-Neto, J.

    2013-01-01

    The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy

  1. Melatonin treatment of pediatric residents for adaptation to night shift work.

    Science.gov (United States)

    Cavallo, Anita; Ris, M Douglas; Succop, Paul; Jaskiewicz, Julie

    2005-01-01

    Night float rotations are used in residency training programs to reduce residents' sleep deprivation. Night shift work, however, is accompanied by deleterious effects on sleep, mood, and attention. To test whether melatonin reduces the deleterious effects of night shift work on sleep, mood, and attention in pediatric residents during night float rotation. Double-blind, randomized, placebo-controlled crossover. Participants took melatonin (3 mg) or a placebo before bedtime in the morning after night shift; completed a sleep diary and an adverse-effects questionnaire daily; and completed the Profile of Mood States and the Conners Continuous Performance Test 3 times in each study week to test mood and attention, respectively. A university-affiliated, tertiary-care pediatric hospital. Healthy second-year pediatric residents working 2 night float rotations. Standardized measures of sleep, mood, and attention. Twenty-eight residents completed both treatments; 17 completed 1 treatment (10 placebo, 7 melatonin). There was not a statistically significant difference in measures of sleep, mood, and 5 of 6 measures of attention during melatonin and placebo treatment. One measure of attention, the number of omission errors, was significantly lower on melatonin (3.0 +/- 9.6) than on placebo (4.5 +/- 17.5) (z = -2.12, P = .03). The isolated finding of improvement of 1 single measure of attention in a test situation during melatonin treatment was not sufficiently robust to demonstrate a beneficial effect of melatonin in the dose used. Other strategies need to be considered to help residents in adaptation to night shift work.

  2. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, S.G.; Peliciari-Garcia, R.A. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil); Takahashi-Hyodo, S.A. [Área de Ciências da Saúde, Universidade Braz Cubas, Mogi das Cruzes, SP (Brazil); Rodrigues, A.C. [Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Amaral, F.G. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil); Berra, C.M. [Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil); Bordin, S.; Curi, R.; Cipolla-Neto, J. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-03-08

    The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

  3. Melatonin against radiation induced free radicals: a study on tissues of Swiss albino mice

    International Nuclear Information System (INIS)

    Bhatia, A.L.; Manda, K.

    2003-01-01

    Full text: Antioxidant enzymes are part of the primary cellular defense against free radicals generated by radiation. Reports on low level chronic administration of melatonin with its antiradiation influence are scanty. Although compelling logic suggests that melatonin may be effective for a variety of disorders, the mode and optimal dose of melatonin is still not clear. Most studies have used doses of supraphysiological blood levels. Present investigation reports that melatonin in relatively lower concentrations increases the mRNA of both superoxide dismutases (SODs) and glutathione peroxidase (GSH-Px) and mediates possibly through receptors. The influence of low dose chronic administration (0.10 mg/Kg body weight/day for 15 days) of melatonin was studied against radiation-induced oxidative stress in 6 to 8 weeks old mice. Just after 24 hours of the last dose in various tissues viz. brain, liver, spleen and kidney were studied for lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px), protein, RNA, DNA and serum phosphatase activity. Radiation induced augmentation in the level of lipid peroxidation, glutathione disulphide (GSSG) and acid phosphatase was significantly ameliorated by pre-irradiation treatment with melatonin. Radiation induced depletion in the level of reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and alkaline phosphatase is significantly averted by melatonin administration. Regression analysis of survival data yielded LD50/30 as 7.16 Gy and 11Gy for control (irradiation alone) and experimental (melatonin + irradiation), respectively. Animals produced a dose reduction factor (DRF) as 1.53. Radiation induced deficit in the body and organ weight was also significantly thwarted in the melatonin pre-treated mice. Results indicate the antioxidative properties of melatonin against the gamma radiation. The findings support the results showing melatonin as a free radical scavenger, and

  4. Melatonin Nanoparticles Adsorbed to Polyethylene Glycol Microspheres as Activators of Human Colostrum Macrophages

    International Nuclear Information System (INIS)

    Hara, C.D.C.P.; Honorio-Frana, A.C.; Fagundes, D.L.G.; Guimares, P.C.L.; Franca, E.L.

    2013-01-01

    The effectiveness of hormones associated with polymeric matrices has amplified the possibility of obtaining new drugs to activate the immune system. Melatonin has been reported as an important immunomodulatory agent that can improve many cell activation processes. It is possible that the association of melatonin with polymers could influence its effects on cellular function. Thus, this study verified the adsorption of the hormone melatonin to polyethylene glycol (PEG) microspheres and analyzed its ability to modulate the functional activity of human colostrum phagocytes. Fluorescence microscopy and flow cytometry analyses revealed that melatonin was able to adsorb to the PEG microspheres. This system increased the release of superoxide and intracellular calcium. There was an increase of phagocytic and microbicidal activity by colostrum phagocytes when in the presence of melatonin adsorbed to PEG microspheres. The modified delivery of melatonin adsorbed to PEG microspheres may be an additional mechanism for its microbicidal activity and represents an important potential treatment for gastrointestinal infections of newborns.

  5. Melatonin Nanoparticles Adsorbed to Polyethylene Glycol Microspheres as Activators of Human Colostrum Macrophages

    Directory of Open Access Journals (Sweden)

    Cristiane de Castro Pernet Hara

    2013-01-01

    Full Text Available The effectiveness of hormones associated with polymeric matrices has amplified the possibility of obtaining new drugs to activate the immune system. Melatonin has been reported as an important immunomodulatory agent that can improve many cell activation processes. It is possible that the association of melatonin with polymers could influence its effects on cellular function. Thus, this study verified the adsorption of the hormone melatonin to polyethylene glycol (PEG microspheres and analyzed its ability to modulate the functional activity of human colostrum phagocytes. Fluorescence microscopy and flow cytometry analyses revealed that melatonin was able to adsorb to the PEG microspheres. This system increased the release of superoxide and intracellular calcium. There was an increase of phagocytic and microbicidal activity by colostrum phagocytes when in the presence of melatonin adsorbed to PEG microspheres. The modified delivery of melatonin adsorbed to PEG microspheres may be an additional mechanism for its microbicidal activity and represents an important potential treatment for gastrointestinal infections of newborns.

  6. Dietary melatonin alters uterine artery hemodynamics in pregnant holstein heifers

    Science.gov (United States)

    The objective was to examine uterine artery hemodynamics and maternal serum profiles in pregnant heifers supplemented with dietary melatonin (MEL) or no supplementation (CON). In addition, melatonin receptor–mediated responses in steroid metabolism were examined using a bovine endometrial epithelial...

  7. A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain

    International Nuclear Information System (INIS)

    Stankov, B.; Moeller, M.; Lucini, V.; Capsono, S.; Fraschini, F.

    1994-01-01

    Dogs kept under controlled photoperiodic conditions of 12h light and 12h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[ 125 I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in the species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 3-thiotriphosphate led to a consequential decrease in the binding density. Collectively, these data show that the dog possesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. 43 refs. 6 figs., 1 tabs

  8. New insights on the spectrophotometric determination of melatonin pKa values and melatonin-βCD inclusion complex formation constant

    Science.gov (United States)

    Zafra-Roldán, A.; Corona-Avendaño, S.; Montes-Sánchez, R.; Palomar-Pardavé, M.; Romero-Romo, M.; Ramírez-Silva, M. T.

    2018-02-01

    Using UV-Vis spectrophotometry a stability study of melatonin at different pH values was done in aqueous media, finding that at acidic pH melatonin is unstable when interacting with the environment, however it becomes stable protecting it from light and oxygen. From the UV-Vis spectra and SQUAD software, melatonin pKa values, in a completely protected aqueous medium, were estimated as 5.777 ± 0.011 and 10.201 ± 0.024. Using the same techniques, the melatonin and β-cyclodextrin inclusion complex formation constants were assessed at pH 3, 7 and 11.5, giving the values of log β = (3.07 ± 0.06), (2.94 ± 0.01) and (3.07 ± 0.06) M- 1, respectively. From the global acidity formation constants and the complexes' formation constants, the molar fractions were determined for each species of MT and MT - βCD, to build the molar fraction-[βCD]-pH 3D diagram and the molar fraction-pH 2D diagrams, where it was possible to observe the predominance of the MT species with and without βCD. A voltammetric study at pH 3, allowed obtaining a value of log β = (3.15 ± 0.01) M- 1, which corroborates that obtained through UV-Vis spectrophotometry, supporting strongly the rationale behind using simple, straightforward techniques.

  9. Concentration-dependent effect of melatonin on DSPC membrane

    Science.gov (United States)

    Sahin, Ipek; Bilge, Duygu; Kazanci, Nadide; Severcan, Feride

    2013-11-01

    The concentration-induced effects of melatonin on distearoyl phosphatidylcholine (DSPC) model membranes were investigated by using two different non-invasive techniques, namely Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). An investigation of the Csbnd H, Cdbnd O and PO2- double bond stretching mode in FTIR spectra and DSC studies reveals that the inclusion of melatonin changes the physical properties of the DSPC multilamellar liposomes (MLVs) by shifting the main phase transition to lower temperatures, abolishing the pretransition, ordering the system in the gel phase and slightly disordering the system in the liquid crystalline phase, increasing the dynamics both in the gel phase and liquid crystalline phases. Melatonin also causes strong hydrogen bonding between Cdbnd O and PO2- groups of lipids and the water molecules around.

  10. Extended Culture of Encapsulated Human Blastocysts in Alginate Hydrogel Containing Decidualized Endometrial Stromal Cells in the Presence of Melatonin.

    Science.gov (United States)

    Arjmand, Fatemeh; Khanmohammadi, Manijeh; Arasteh, Shaghayegh; Mohammadzadeh, Afsaneh; Kazemnejad, Somaieh; Akhondi, Mohammad-Mehdi

    2016-10-01

    Extended in vitro culture of human embryos beyond blastocyst stage could serve as a tool to explore the molecular and physiological mechanisms underlying embryo development and to identify factors regulating pregnancy outcomes. This study presents the first report on the maintenance of human embryo in vitro by alginate co-encapsulation of human blastocyst and decidualized endometrial stromal cells (EnSCs) under melatonin-fortified culture conditions. The effectiveness of the 3D culture system was studied through monitoring of embryo development in terms of survival time, viability, morphological changes, and production of the two hormones of 17b-oestradiol and human chorionic gonadotropin. The embryo structural integrity was preserved during alginate encapsulation; however, only 23 % of the encapsulated embryos could retain in the hydrogels over time and survived until day 4 post-encapsulation. The culture medium fortification with melatonin significantly elevated the maintenance rate of expanded embryos in alginate beads by 65 % and prolonged survival time of human embryos to day 5. Furthermore, embryo co-culture with EnSCs using melatonin-fortified medium increased the survival time of encapsulated embryos to 44 %. The levels of two measured hormones significantly rose at day 4 in comparison with day 2 post-encapsulation especially in the group co-encapsulated with EnSCs and cultivated in melatonin-fortified culture medium. These data are the first evidence representing in vitro development of human embryos until day 10 post-fertilization. This achievement can facilitate the investigation of the mechanisms regulating human embryo development.

  11. Adaptations of the aging animal to exercise: role of daily supplementation with melatonin.

    Science.gov (United States)

    Mendes, Caroline; Lopes, Ana Maria de Souza; do Amaral, Fernanda Gaspar; Peliciari-Garcia, Rodrigo A; Turati, Ariane de Oliveira; Hirabara, Sandro M; Scialfa Falcão, Julieta H; Cipolla-Neto, José

    2013-10-01

    The pineal gland, through melatonin, seems to be of fundamental importance in determining the metabolic adaptations of adipose and muscle tissues to physical training. Evidence shows that pinealectomized animals fail to develop adaptive metabolic changes in response to aerobic exercise and therefore do not exhibit the same performance as control-trained animals. The known prominent reduction in melatonin synthesis in aging animals led us to investigate the metabolic adaptations to physical training in aged animals with and without daily melatonin replacement. Male Wistar rats were assigned to four groups: sedentary control (SC), trained control (TC), sedentary treated with melatonin (SM), and trained treated with melatonin (TM). Melatonin supplementation lasted 16 wk, and the animals were subjected to exercise during the last 8 wk of the experiment. After euthanasia, samples of liver, muscle, and adipose tissues were collected for analysis. Trained animals treated with melatonin presented better results in the following parameters: glucose tolerance, physical capacity, citrate synthase activity, hepatic and muscular glycogen content, body weight, protein expression of phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and protein kinase activated by adenosine monophosphate (AMPK) in the liver, as well as the protein expression of the glucose transporter type 4 (GLUT4) and AMPK in the muscle. In conclusion, these results demonstrate that melatonin supplementation in aging animals is of great importance for the required metabolic adaptations induced by aerobic exercise. Adequate levels of circulating melatonin are, therefore, necessary to improve energetic metabolism efficiency, reducing body weight and increasing insulin sensitivity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

    Science.gov (United States)

    Sharan, Kunal; Lewis, Kirsty; Furukawa, Takahisa; Yadav, Vijay K

    2017-09-01

    Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites, viz. serotonin and melatonin, that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected. Skeletal analysis of the mice deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/- and MT2-/- mice showed a cell intrinsic defect in the proliferation, differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT counterparts, and the mutant cells did not respond to melatonin addition. Finally, we demonstrate that daily oral administration of melatonin can increase bone accrual during growth and can cure ovariectomy-induced structural and functional degeneration of bone by specifically increasing bone formation. By identifying pineal-derived melatonin as a regulator of bone mass through MT2 receptors, this study expands the role played by tryptophan derivatives in the regulation of bone mass and underscores its therapeutic relevance in postmenopausal osteoporosis. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

  13. Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

    Directory of Open Access Journals (Sweden)

    Singh Rajesh

    2009-04-01

    Full Text Available Abstract Background Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA – a β adrenergic blocker, is known to perform chemical pinealectomy (Px by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti. Results Aged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC, Lymphocytes Count (LC, % stimulation ratio of splenocytes (% SR against T cell mitogen concanavalin A (Con A, delayed type hypersensitivity (DTH to oxazolone when compared to young adult group. Melatonin administration (25 μg/100 g body mass/day significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels. Conclusion PCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters

  14. Altered circadian rhythm of melatonin concentrations in hypocretin-deficient men.

    NARCIS (Netherlands)

    Donjacour, C.E.; Kalsbeek, A.; Overeem, S.; Lammers, G.J.; Pevet, P.; Bothorel, B.; Pijl, H.; Aziz, N.A.

    2012-01-01

    Hypocretin deficiency causes narcolepsy. It is unknown whether melatonin secretion is affected in this sleep disorder. Therefore, in both narcolepsy patients and matched controls, the authors measured plasma melatonin levels hourly for 24 h before and after 5 days of sodium oxybate (SXB)

  15. Physiological melatonin levels in healthy older people : A systematic review

    NARCIS (Netherlands)

    Scholtens, Rikie M.; van Munster, Barbara C.; van Kempen, Marijn F.; de Rooij, Sophia E. J. A.

    Objective: Melatonin plays a major role in maintaining circadian rhythm. Previous studies showed that its secretion pattern and levels could be disturbed in persons with dementia, psychiatric disorders, sleep disorders or with cancer. Also ageing is a factor that could alter melatonin levels,

  16. Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

    Science.gov (United States)

    Martarelli, D; Casettari, L; Shalaby, K S; Soliman, M E; Cespi, M; Bonacucina, G; Fagioli, L; Perinelli, D R; Lam, J K W; Palmieri, G F

    2016-01-01

    Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

  17. Effects of moderate and heavy endurance exercise on nocturnal HRV.

    Science.gov (United States)

    Hynynen, E; Vesterinen, V; Rusko, H; Nummela, A

    2010-06-01

    This study examined the effects of endurance exercise on nocturnal autonomic modulation. Nocturnal R-R intervals were collected after a rest day, after a moderate endurance exercise and after a marathon run in ten healthy, physically active men. Heart rate variability (HRV) was analyzed as a continuous four-hour period starting 30 min after going to bed for sleep. In relation to average nocturnal heart rate after rest day, increases to 109+/-6% and 130+/-11% of baseline were found after moderate endurance exercise and marathon, respectively. Standard deviation of R-R intervals decreased to 90+/-9% and 64+/-10%, root-mean-square of differences between adjacent R-R intervals to 87+/-10% and 55+/-16%, and high frequency power to 77+/-19% and 34+/-19% of baseline after moderate endurance exercise and marathon, respectively. Also nocturnal low frequency power decreased to 56+/-26% of baseline after the marathon. Changes in nocturnal heart rate and HRV suggest prolonged dose-response effects on autonomic modulation after exercises, which may give useful information on the extent of exercise-induced nocturnal autonomic modulation and disturbance to the homeostasis.

  18. In vitro development rate of preimplantation rabbit embryos cultured with different levels of melatonin.

    Science.gov (United States)

    Mehaisen, Gamal Mohamed Kamel; Saeed, Ayman Moustafa

    2015-02-01

    This study aimed to investigate the effect of melatonin supplementation at different levels in culture medium on embryo development in rabbits. Embryos of 2-4 cells, 8-16 cells and morula stages were recovered from nulliparous Red Baladi rabbit does by laparotomy technique 24, 48 and 72 h post-insemination, respectively. Normal embryos from each stage were cultured to hatched blastocyst stages in either control culture medium (TCM-199 + 20% fetal bovine serum) or control supplemented with melatonin at 10(-3) M, 10(-6) M or 10(-9) M. No effect of melatonin was found on development of embryos recovered at 24 h post-insemination. The high level of melatonin at 10(-3) M adversely affected the in vitro development rates of embryos recovered at 48 h post-insemination (52 versus 86, 87 and 80% blastocyst rate; 28 versus 66, 78 and 59% hatchability rate for 10(-3) M versus 10(-9) M, 10(-6) M and control, respectively, P< 0.05). At the morula stage, melatonin at 10-3 M significantly increased the in vitro development of embryos (92% for 10(-3) M versus 76% for control, P < 0.05), while the hatchability rate of these embryos was not improved by melatonin (16-30% versus 52% for melatonin groups versus control, P < 0.05). Results show that a moderate level of melatonin (10(-6) M) may improve the development and hatchability rates of preimplantation rabbit embryos. The addition of melatonin at a 10-3 M concentration enhances the development of rabbit morulae but may negatively affect the development of earlier embryos. More studies are needed to optimize the use of melatonin in in vitro embryo culture in rabbits.

  19. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Hikichi T

    2011-05-01

    Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

  20. Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep.

    Science.gov (United States)

    Yu, Bing; Huang, Mingzhu; Zhang, Xu; Ma, Hongwei; Peng, Miao; Guo, Qiyong

    2017-05-01

    A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole-brain cerebral metabolic rate of oxygen (CMRO 2 ), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase-contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age- and sex-matched control volunteers (n = 39) during natural sleep to assess whole-brain CMRO 2 , CBF, OEF, and arousal from sleep scores. Results showed that whole-brain CMRO 2 and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp 38:2532-2539, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

    Science.gov (United States)

    Hoffmeister, Cristiane RD; Durli, Taís L.; Schaffazick, Scheila R.; Raffin, Renata P.; Bender, Eduardo A.; Beck, Ruy CR; Pohlmann, Adriana R.; Guterres, Sílvia S.

    2012-05-01

    The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% ( w/ v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

  2. Characterization of melatonin binding sites in the Harderian gland and median eminence of the rat

    International Nuclear Information System (INIS)

    Lopez-Gonzalez, M.A.; Calvo, J.R.; Rubio, A.; Goberna, R.; Guerrero, J.M.

    1991-01-01

    The characterization of specific melatonin binding sites in the Harderian gland (HG) and median eminence (ME) of the rat was studied using [ 125 I]melatonin. Binding of melatonin to membrane crude preparations of both tissues was dependent on time and temperature. Thus, maximal binding was obtained at 37 degree C after 30-60 min incubation. Binding was also dependent on protein concentration. The specific binding of [ 125 I]melatonin was saturable, exhibiting only the class of binding sites in both tissues. The dissociation constants (Kd) were 170 and 190 pM for ME and HG, respectively. The concentration of the binding sites in ME was 8 fmol/mg protein, and in the HG 4 fmol/mg protein. In competition studies, binding of [ 125 I]melatonin to ME or HG was inhibited by increasing concentration of native melatonin; 50% inhibition was observed at about 702 and 422 nM for ME and HG, respectively. Additionally, the [ 125 I]melatonin binding to the crude membranes was not affected by the addition of different drugs such as norepinephrine, isoproterenol, phenylephrine, propranolol, or prazosin. The results confirm the presence of melatonin binding sites in median eminence and show, for the first time, the existence of melatonin binding sites in the Harderian gland

  3. Analysis of miRNA expression profiles in melatonin-exposed GC-1 spg cell line.

    Science.gov (United States)

    Zhu, Xiaoling; Chen, Shuxiong; Jiang, Yanwen; Xu, Ying; Zhao, Yun; Chen, Lu; Li, Chunjin; Zhou, Xu

    2018-02-05

    Melatonin is an endocrine neurohormone secreted by pinealocytes in the pineal gland. It exerts diverse physiological effects, such as circadian rhythm regulator and antioxidant. However, the functional importance of melatonin in spermatogenesis regulation remains unclear. The objectives of this study are to: (1) detect melatonin affection on miRNA expression profiles in GC-1 spg cells by miRNA deep sequencing (DeepSeq) and (2) define melatonin affected miRNA-mRNA interactions and associated biological processes using bioinformatics analysis. GC-1 spg cells were cultured with melatonin (10 -7 M) for 24h. DeepSeq data were validated using quantitative real-time reverse transcription polymerase chain reaction analysis (qRT-PCR). A total of 176 miRNA expressions were found to be significantly different between two groups (fold change of >2 or melatonin could regulate the expression of miRNA to perform its physiological effects in GC-1 spg cells. These results should be useful to investigate the biological function of miRNAs regulated by melatonin in spermatogenesis and testicular germ cell tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer.

    Science.gov (United States)

    Asghari, Mohammad Hossein; Moloudizargari, Milad; Ghobadi, Emad; Fallah, Marjan; Abdollahi, Mohammad

    2017-09-15

    Gastric cancer (GC) is a predominant malignancy with a high mortality rate affecting a large population worldwide. The etiology of GC is multifactorial spanning from various genetic determinants to different environmental causes. Current tretaments of GC are not efficient enough and require improvements to minimize the adverse effects. Melatonin, a naturally occurring compound with known potent inhibitory effects on cancer cells is one of the major candidates which can be recruited herein. Here we reviewed the articles conducted on the therapeutic effects of melatonin in gastric cancer in various models. The results are classified according to different aspects of cancer pathogenesis and the molecular mechanisms by which melatonin exerts its effects. Melatonin could be used to combat GC exploiting its effects on multiple aspects of its pathogenesis, including formation of cancer cells, tumor growth and angiogenesis, differentiation and metastasis as well as enhancing the anti-tumor immunity. Melatonin is a pleiotropic anti-cancer molecule that affects malignant cells via multiple mechanisms. It has been shown to benefit cancer patients indirectly by reducing side effects of current therapies which have been discussed in this review. This field of research is still underdeveloped and may serve as an interesting subject for further studies aiming at the molecular mechanisms of melatonin and novel treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Effects of Exogenous Melatonin on Sperm Characteristics of ...

    African Journals Online (AJOL)

    Twelve West African Dwarf Goat (WADG) bucks (12-15months aged) were randomly allotted to four groups and were caged, individually. In the melatonin treated groups (M), bucks were orally administrated 3 mg, 6 mg and 9 mg of melatonin per animal per day between 9.00 and 10.00 a.m. The control received no ...

  6. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  7. Physiological melatonin levels in healthy older people: A systematic review

    NARCIS (Netherlands)

    Scholtens, Rikie M.; van Munster, Barbara C.; van Kempen, Marijn F.; de Rooij, Sophia E. J. A.

    2016-01-01

    Melatonin plays a major role in maintaining circadian rhythm. Previous studies showed that its secretion pattern and levels could be disturbed in persons with dementia, psychiatric disorders, sleep disorders or with cancer. Also ageing is a factor that could alter melatonin levels, although previous

  8. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Juhyun Song

    2015-01-01

    Full Text Available Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs. Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.

  9. Sleep-wake and melatonin pattern in craniopharyngioma patients.

    Science.gov (United States)

    Pickering, Line; Jennum, Poul; Gammeltoft, Steen; Poulsgaard, Lars; Feldt-Rasmussen, Ulla; Klose, Marianne

    2014-06-01

    To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. Cross-sectional study. A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36. Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P≤0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P≤0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P≤0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue. Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei. © 2014 European Society of Endocrinology.

  10. Сircadian rhythm and metabolic effects of melatonin

    Directory of Open Access Journals (Sweden)

    Denis Igorevich Burchakov

    2015-02-01

    Full Text Available Sleep is a highly important process, required for normal organ and system function. Researchers assume, that during sleep brain shifts to internal body signals. Therefore, any sleep disturbance will disrupt health. Industrial and post-industrial society links high stress level and sleep problems. Excess light stimulation in living space, including bedroom, disorganize circadian rhythm of melatonin. Besides regulation this hormone has antioxidant and adaptogen functions. From psychological standpoint the same high-stress social context depletes the adaptation resources. To normalize sleep function we can utilize both sleep hygiene measures and modern pharmacotherapy. There are melatonin-based drugs, which help to restore sleep-wake cycle, augment adaptive capability and in some cases empower the existing treatment for specific somatic maladies. From a clinical and chronobiological standpoint melatonin is useful in broad spectrum of disorders.

  11. The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development

    Directory of Open Access Journals (Sweden)

    Yunho Jin

    2018-01-01

    Full Text Available The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD.

  12. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

    Science.gov (United States)

    Bumb, J M; Enning, F; Mueller, J K; van der List, Till; Rohleder, C; Findeisen, P; Noelte, I; Schwarz, E; Leweke, F M

    2016-07-01

    Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. In CSF, melatonin levels were significantly decreased in bipolar (Pdepressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Melatonin, Aging and Breast Cancer

    National Research Council Canada - National Science Library

    Hill, Steven

    2001-01-01

    ... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...

  14. Regulatory Effect of Melatonin on Cytokine Disturbances in the Pristane-Induced Lupus Mice

    Directory of Open Access Journals (Sweden)

    Ling-ling Zhou

    2010-01-01

    Full Text Available Systemic lupus erythematosus (SLE develops in relation to many environmental factors. In our opinion, it is more important to investigate the effect of melatonin on the environmental- related SLE. In the present study, 0.5 ml pristane were used to induce SLE in female BALB/c mice. Melatonin (0.01, 0.1, 1.0 mg/kg was orally administered immediately after pristane-injection for 24 weeks. IgM anti ssDNA and histone antibodies were detected after 0, 1, 2, 4, 8 weeks pristane injection. The levels of IL-2, IL-6 and IL-13 were detected after 24 weeks. Renal lesions were also observed. The results showed that melatonin antagonized the increasing levels of IgM anti ssDNA and histone autoantibodies. Melatonin could also decrease the IL-6 and IL-13 production and increase the IL-2 production. Besides, melatonin could lessen the renal lesions caused by pristane. These results suggested that melatonin has a beneficial effect on pristane-induced lupus through regulating the cytokines disturbances.

  15. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia

    DEFF Research Database (Denmark)

    Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene

    2015-01-01

    Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment...... with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual...... X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin...

  16. Early prophylactic and treatment role of melatonin against certain biochemical disorders in irradiated rats

    International Nuclear Information System (INIS)

    El-Massry, F.S.

    2005-01-01

    The aim of the present study is to evaluate the possible early prophylactic and therapeutic role of melatonin on irradiated rats. The experimental animals were divided into five groups: control, injected intraperitoneally with melatonin (10 mg/ kg b.wt.), irradiated at 6 Gy, injected with melatonin before irradiation and injected with melatonin after gamma irradiation. Blood, liver and brain samples from rats were collected at three time intervals of 7, 10, 14 days after terminating all treatments. Protein content and glutathione were estimated in blood and tissues, whereas testosterone and cortisol were assayed in blood of rats after whole body gamma irradiation at 6 Gy. Administration of melatonin (10 mg/kg) before whole body gamma irradiation markedly reduced the radiation injury and controlled the changes in most of the studied parameters, but following the administration of melatonin after irradiation, there were no changes in these parameters

  17. Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats.

    Science.gov (United States)

    Takahashi, Tatiane T; Vengeliene, Valentina; Spanagel, Rainer

    2017-06-01

    Melatonin is a hormone involved in the entrainment of circadian rhythms, which appears dysregulated in drug users. Further, it has been demonstrated that melatonin can modulate the reinforcing effects of several drugs of abuse and may therefore play a role in drug addiction. Here, we investigated whether administration of melatonin reduces relapse-like behavior and the motivation to seek cocaine in rats. Male Sprague-Dawley rats were submitted to long-term cocaine self-administration training. Thereafter, melatonin effects were assessed on: (1) the motivation to work for cocaine in the break point test, (2) the relapse-like behavior in the cue-induced reinstatement test, (3) the distance traveled in the open field test, and (4) sucrose preference in a two-bottle choice paradigm. Melatonin, 25 or 50 mg/kg, was injected 3-4 h after the dark phase onset, 30 min prior to each test. Both doses of melatonin decreased the number of active pokes in both break point and cue-induced reinstatement tests, demonstrating that melatonin can reduce the cocaine-seeking behavior and the motivation to work for cocaine. Administration of the higher dose of this hormone, however, significantly reduced the number of inactive pokes during the cue-induced reinstatement test and tended to reduce animals' locomotor activity in the open field test. Sucrose preference was unchanged in both vehicle- and melatonin-treated animal groups. Our data suggest that melatonin administration may lower the risk of relapse triggered by cues in cocaine-experienced animals.

  18. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    Science.gov (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  19. The reduction in circulating levels of melatonin may be associated with the development of preeclampsia.

    Science.gov (United States)

    Zeng, K; Gao, Y; Wan, J; Tong, M; Lee, A C; Zhao, M; Chen, Q

    2016-11-01

    Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy.

  20. Exogenous Melatonin Improves Plant Iron Deficiency Tolerance via Increased Accumulation of Polyamine-Mediated Nitric Oxide.

    Science.gov (United States)

    Zhou, Cheng; Liu, Zhi; Zhu, Lin; Ma, Zhongyou; Wang, Jianfei; Zhu, Jian

    2016-10-25

    Melatonin has recently been demonstrated to play important roles in the regulation of plant growth, development, and abiotic and biotic stress responses. However, the possible involvement of melatonin in Fe deficiency responses and the underlying mechanisms remained elusive in Arabidopsis thaliana . In this study, Fe deficiency quickly induced melatonin synthesis in Arabidopsis plants. Exogenous melatonin significantly increased the soluble Fe content of shoots and roots, and decreased the levels of root cell wall Fe bound to pectin and hemicellulose, thus alleviating Fe deficiency-induced chlorosis. Intriguingly, melatonin treatments induced a significant increase of nitric oxide (NO) accumulation in roots of Fe-deficient plants, but not in those of polyamine-deficient ( adc2-1 and d-arginine-treated) plants. Moreover, the melatonin-alleviated leaf chlorosis was blocked in the polyamine- and NO-deficient ( nia1nia2noa1 and c-PTIO-treated) plants, and the melatonin-induced Fe remobilization was largely inhibited. In addition, the expression of some Fe acquisition-related genes, including FIT1 , FRO2 , and IRT1 were significantly up-regulated by melatonin treatments, whereas the enhanced expression of these genes was obviously suppressed in the polyamine- and NO-deficient plants. Collectively, our results provide evidence to support the view that melatonin can increase the tolerance of plants to Fe deficiency in a process dependent on the polyamine-induced NO production under Fe-deficient conditions.

  1. The circadian variations of serum melatonin and testosterone levels in starved rats

    International Nuclear Information System (INIS)

    Ostrowska, Z.; Zwirska-Korczala, K.; Marek, B.; Buntner, B.

    1995-01-01

    Circadian variations of serum melatonin and testosterone in sexually mature male Wistar rats after a one-week starvation were examined using, the radioimmunoassay RIA method at 2-h intervals under 12:12 h light-dark cycle. The population mean cosinor analysis justified the existence of a significant circadian rhythm of melatonin and testosterone in starved rats, whereas their mean 24-h concentration was lower. Both melatonin and testosterone circadian rhythms were disturbed with phase shifts from 1.58 to 16.59 h and from 18.00 to 3.49 h, respectively. A significant correlation between the melatonin and testosterone concentrations during day/night cycle was observed. (author). 38 refs, 4 figs, 1 tab

  2. Melatonin induction and its role in high light stress tolerance in Arabidopsis thaliana.

    Science.gov (United States)

    Lee, Hyoung Yool; Back, Kyoungwhan

    2018-05-16

    In plants, melatonin is a potent bioactive molecule involved in the response against various biotic and abiotic stresses. However, little is known of its defensive role against high light (HL) stress. In this study, we found that melatonin was transiently induced in response to HL stress in Arabidopsis thaliana with a simultaneous increase in the expression of melatonin biosynthetic genes, including serotonin N-acetyltransferase1 (SNAT1). Transient induction of melatonin was also observed in the flu mutant, a singlet oxygen ( 1 O 2 )-producing mutant, upon light exposure, suggestive of melatonin induction by chloroplastidic 1 O 2 against HL stress. An Arabidopsis snat1 mutant was devoid of melatonin induction upon HL stress, resulting in high susceptibility to HL stress. Exogenous melatonin treatment mitigated damage caused by HL stress in the snat1 mutant by reducing O 2 - production and increasing the expression of various ROS-responsive genes. In analogy, an Arabidopsis SNAT1-overexpressing line showed increased tolerance of HL stress concomitant with a reduction in malondialdehyde and ion leakage. A complementation line expressing an Arabidopsis SNAT1 genomic fragment in the snat1 mutant completely restored HL stress susceptibility in the snat1 mutant to levels comparable to that of wild-type Col-0 plants. The results of the analysis of several Arabidopsis genetic lines reveal for the first time at the genetic level that melatonin is involved in conferring HL stress tolerance in plants. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Tingting Jiang

    2016-01-01

    Full Text Available Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR. Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p. injection of STZ (60 mg/kg in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p. was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL. Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS, was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.

  4. Stimulatory Effects of Melatonin on Porcine In Vitro Maturation Are Mediated by MT2 Receptor

    Directory of Open Access Journals (Sweden)

    Sanghoon Lee

    2018-05-01

    Full Text Available Melatonin is a multifunctional molecule with numerous biological activities. The fact that melatonin modulates the functions of porcine granulosa cells via the MT2 receptor suggests the possibility of MT2 receptor-mediation for melatonin to promote cumulus expansion of porcine cumulus-oocyte complexes (COCs. Therefore, we investigated the presence of MT2 in porcine COCs, and the effects of melatonin with or without selective MT2 antagonists (luzindole and 4-P-PDOT on this process; COCs underwent in vitro maturation culturing with six different conditions (control, melatonin, luzindole, 4-P-PDOT, melatonin + luzindole or melatonin + 4-P-PDOT. Cumulus expansion, oocyte nuclear maturation, and subsequent embryo development after parthenogenetic activation (PA were evaluated. In experiment 1, MT2 was expressed in both oocytes and cumulus cells. In experiment 2, melatonin significantly increased the proportion of complete cumulus expansion (degree 4, which was inhibited by simultaneous addition of either luzindole or 4-P-PDOT. A similar pattern was observed in the expression of genes related to cumulus expansion, apoptosis, and MT2. In experiment 3, no significant difference was observed in immature, degenerate, and MII oocyte rates among the groups. In experiment 4, melatonin significantly increased blastocyst formation rates and total blastocyst cell numbers after PA, but these effects were abolished when either luzindole or 4-P-PDOT was added concomitantly. In conclusion, our results indicate that the MT2 receptor mediated the stimulatory effects of melatonin on porcine cumulus expansion and subsequent embryo development.

  5. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue.

    Science.gov (United States)

    Liu, Zhenjiang; Gan, Lu; Xu, Yatao; Luo, Dan; Ren, Qian; Wu, Song; Sun, Chao

    2017-08-01

    Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Comparison of Melatonin Profile and Alertness of Firefighters with Different Work Schedules

    Science.gov (United States)

    Kazemi, Reza; Zare, Sajad

    2018-01-01

    Introduction: A two-shift work schedule with different rotations is common among firefighters in Iranian petrochemical companies. This study compared salivary melatonin and sleepiness on the last night before turning to day shift at 19:00, 23:00, 3:00, and 7:00 among petrochemical firefighters (PFFs) working seven and four consecutive night shifts. Methods: Sixty four PFFs working in the petrochemical industry were selected. To measure melatonin, saliva samples were taken, whereas the KSS index was used to assess sleepiness. Chi-square and independent samples t-test were carried out to analyze the data, and generalized linear model (GLM) was employed to determine the effect of confounding factors such as lighting and caffeine. Results: The levels of melatonin at 3:00 and 7:00, and the overall changes during the shift in the two shift patterns under the study were different (P shift patterns, while the effects of lighting and caffeine on melatonin changes were not significant (P > 0.05). Conclusion: It seems that a slow shift rotation is better because it reduces the secretion of melatonin (hence reducing sleepiness during the night) and changes the peak of melatonin secretion to the daytime, which is a sign of adaptation.

  7. Glucose-based microbial production of the hormone melatonin in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Germann, Susanne M; Baallal Jacobsen, Simo A; Schneider, Konstantin; Harrison, Scott J; Jensen, Niels B; Chen, Xiao; Stahlhut, Steen G; Borodina, Irina; Luo, Hao; Zhu, Jiangfeng; Maury, Jérôme; Forster, Jochen

    2016-05-01

    Melatonin is a natural mammalian hormone that plays an important role in regulating the circadian cycle in humans. It is a clinically effective drug exhibiting positive effects as a sleep aid and a powerful antioxidant used as a dietary supplement. Commercial melatonin production is predominantly performed by complex chemical synthesis. In this study, we demonstrate microbial production of melatonin and related compounds, such as serotonin and N-acetylserotonin. We generated Saccharomyces cerevisiae strains that comprise heterologous genes encoding one or more variants of an L-tryptophan hydroxylase, a 5-hydroxy-L-tryptophan decarboxylase, a serotonin acetyltransferase, an acetylserotonin O-methyltransferase, and means for providing the cofactor tetrahydrobiopterin via heterologous biosynthesis and recycling pathways. We thereby achieved de novo melatonin biosynthesis from glucose. We furthermore accomplished increased product titers by altering expression levels of selected pathway enzymes and boosting co-factor supply. The final yeast strain produced melatonin at a titer of 14.50 ± 0.57 mg L(-1) in a 76h fermentation using simulated fed-batch medium with glucose as sole carbon source. Our study lays the basis for further developing a yeast cell factory for biological production of melatonin. © 2015 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

    Science.gov (United States)

    Sanchez-Barcelo, Emilio J; Rueda, Noemi; Mediavilla, María D; Martinez-Cue, Carmen; Reiter, Russel J

    2017-11-20

    Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

    Science.gov (United States)

    Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Adachi, Lauren Naomi Spezia; de Macedo, Isabel Cristina; Cioato, Stefania Giotti; de Freitas, Joice S; de Souza, Andressa; Quevedo, Alexandre; Caumo, Wolnei; Torres, Iraci Lucena da Silva

    2016-10-01

    Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

  10. Paroxysmal nocturnal hemoglobinuria (PNH)

    Science.gov (United States)

    ... help slow the breakdown of red blood cells. Blood transfusions may be needed. Supplemental iron and folic acid ... is no known way to prevent this disorder. Alternative Names PNH Images Blood cells References Brodsky RA. Proxymal nocturnal hemoglobinuria. In: ...

  11. Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair

    DEFF Research Database (Denmark)

    Gögenür, Ismail; Kücükakin, Bülent; Panduro Jensen, Leif

    2014-01-01

    The aim was to examine the effect of perioperative melatonin treatment on clinical cardiac morbidity and markers of myocardial ischemia in patients undergoing elective surgery for abdominal aortic aneurism. Reperfusion injury results in increased cardiac morbidity in patients undergoing surgery...... for abdominal aortic aneurisms (AAA). A randomized, placebo-controlled, clinical trial including patients undergoing surgery for AAA was performed. The patients received by infusion over a 2-hr period either, 50 mg melatonin or placebo intra-operatively, and 10 mg melatonin or placebo orally, the first three...... by Holter monitoring. A total of 26 patients received melatonin, while 24 received placebo. A significant reduction in cardiac morbidity was seen in the melatonin-treated patients compared with those given placebo [4% versus 29% (P = 0.02)]. Five patients (19%) who received melatonin had increased Tp...

  12. Nocturnal vision and landmark orientation in a tropical halictid bee.

    Science.gov (United States)

    Warrant, Eric J; Kelber, Almut; Gislén, Anna; Greiner, Birgit; Ribi, Willi; Wcislo, William T

    2004-08-10

    Some bees and wasps have evolved nocturnal behavior, presumably to exploit night-flowering plants or avoid predators. Like their day-active relatives, they have apposition compound eyes, a design usually found in diurnal insects. The insensitive optics of apposition eyes are not well suited for nocturnal vision. How well then do nocturnal bees and wasps see? What optical and neural adaptations have they evolved for nocturnal vision? We studied female tropical nocturnal sweat bees (Megalopta genalis) and discovered that they are able to learn landmarks around their nest entrance prior to nocturnal foraging trips and to use them to locate the nest upon return. The morphology and optics of the eye, and the physiological properties of the photoreceptors, have evolved to give Megalopta's eyes almost 30 times greater sensitivity to light than the eyes of diurnal worker honeybees, but this alone does not explain their nocturnal visual behavior. This implies that sensitivity is improved by a strategy of photon summation in time and in space, the latter of which requires the presence of specialized cells that laterally connect ommatidia into groups. First-order interneurons, with significantly wider lateral branching than those found in diurnal bees, have been identified in the first optic ganglion (the lamina ganglionaris) of Megalopta's optic lobe. We believe that these cells have the potential to mediate spatial summation. Despite the scarcity of photons, Megalopta is able to visually orient to landmarks at night in a dark forest understory, an ability permitted by unusually sensitive apposition eyes and neural photon summation.

  13. Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation.

    Science.gov (United States)

    Li, Zheng; Li, Xingye; Chan, Matthew T V; Wu, William Ka Kei; Tan, DunXian; Shen, Jianxiong

    2017-09-01

    Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  14. Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function.

    Science.gov (United States)

    Mendivil-Perez, Miguel; Soto-Mercado, Viviana; Guerra-Librero, Ana; Fernandez-Gil, Beatriz I; Florido, Javier; Shen, Ying-Qiang; Tejada, Miguel A; Capilla-Gonzalez, Vivian; Rusanova, Iryna; Garcia-Verdugo, José M; Acuña-Castroviejo, Darío; López, Luis Carlos; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Ferrer, José M; Escames, Germaine

    2017-09-01

    Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis

    International Nuclear Information System (INIS)

    Adriaens, I.; Jacquet, P.; Cortvrindt, R.; Janssen, K.; Smitz, J.

    2006-01-01

    Chemo and/or radiotherapy applied to young cancer patients most often have severe effects upon female fertility. Today, few options are available to protect ovarian function in females. However, these options are either ineffective, belong to the field of experimental research or/and are not applicable to all patients. Drugs that could protect the oocyte and its surrounding feeder cells from damage can be of great importance. Melatonin, being an important indirect antioxidant and a powerful direct free radical scavenger could be such a reagent. This paper reports the direct effects of different melatonin concentrations (range: 1 nM to 2 mM) on folliculogenesis and oogenesis of in vitro cultured mouse ovarian follicles. Early secondary mouse follicles were cultured in vitro for 12 days under different melatonin regimes. Every fourth day, survival rates were scored, follicles were morphologically evaluated and medium was collected for steroid analyses. On day 12, in vitro ovulation was induced by hCG/EGF. Eighteen hours later, oocytes were measured, oocyte maturation was evaluated and normality of spindle and chromosomes ascertained. Results obtained in this study indicated that 2 mM melatonin is toxic. One mM negatively influenced oocyte maturation capacity. In the presence of 100 μM melatonin, androstenedione and progesterone were increased whereas estradiol was not influenced. Lower melatonin concentrations had no effect on the evaluated parameters. These data indicate an effect of melatonin on theca cell steroidogenesis. For prophylactic use, a dose of 10 μM could be suitable to reduce oxidative stress in cultured follicles

  16. The pineal neurohormone melatonin and its physiologic opiatergic immunoregulatory role

    Directory of Open Access Journals (Sweden)

    Georges J. M. Maestroni

    1987-01-01

    Full Text Available The pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. The main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the night darkness hours. We have recently reported that melatonin exerts important immuno regulatory functions. Here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. This effect seems to be mediated by antigen-activated T cells via an opiatergic mechanism.

  17. Melatonin ve Bağışıklık Sistemi

    OpenAIRE

    ÇETİN, E.

    2005-01-01

    Melatonin, pineal bezin beta adrenerjik reseptörlerinin aktivasyonu ile triptofandan sentezlenen bir hormondur.Üretim ve salınımı karanlık ile başlar ve aydınlıkla sona erer. Melatonin, birçok biyolojik fonksiyonun düzenlenmesinderol oynar. Bu derlemede melatonin hakkında genel bilgiler verilerek, melatoninin lenfoid dokular, humoral bağışıklık,hücresel bağışıklık ve kanser üzerine etkileri tartışılmıştır

  18. The role of melatonin in mood disorders

    Directory of Open Access Journals (Sweden)

    De Berardis D

    2015-11-01

    Full Text Available Domenico De Berardis,1–3 Laura Orsolini,3–5 Nicola Serroni,1 Gabriella Girinelli,1–3 Felice Iasevoli,3–6 Carmine Tomasetti,3–6 Monica Mazza,3–7 Alessandro Valchera,3–8 Michele Fornaro,9 Giampaolo Perna,10–12 Monica Piersanti,13Marco Di Nicola,14 Marilde Cavuto,15 Giovanni Martinotti,2 Massimo Di Giannantonio21NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G Mazzini", Teramo, Italy; 2Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University G d'Annunzio, Chieti, Italy; 3Polyedra, Teramo, Italy; 4United Hospitals, Academic Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy; 5School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire, UK; 6Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Naples, Italy; 7Department of Health Sciences, University of L'Aquila, L'Aquila, Italy; 8Villa S Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy; 9Department of Scienze della Formazione, University of Catania, Catania, Italy; 10Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, Como, Italy; 11Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, the Netherlands; 12Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA; 13Hospital Pharmacy, Hospital G Mazzini, ASL 4 Teramo, Italy; 14Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, Rome, Italy; 15IASM, L'Aquila, ItalyAbstract: Melatonin (N-acetyl-5-methoxytryptamine has been discovered as a hormone secreted by the pineal gland, even though it is also synthetized in various other organs, tissues, and cells. The circadian rhythm of

  19. Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

    Directory of Open Access Journals (Sweden)

    Ganka Bekyarova

    2017-04-01

    Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

  20. Melatonin protects uterus and oviduct exposed to nicotine in mice

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

    Full Text Available Smoking is associated with higher infertility risk. The aim of this study was to evaluate protective effects of melatonin on the uterus and oviduct in mice exposed to nicotine. Adult female mice (n=32 were divided into four groups. Group A: control animals received normal saline, Group B: injected with nicotine 40 μg/kg, Group C: injected with melatonin 10 μg, Group D: injected with nicotine 40 μg/kg and melatonin 10 μg. All animals were treated over 15 days intraperitoneally. On the 16th day, animals in the estrus phase were dissected and their uterus and oviducts were removed. Immunohistochemistry was recruited for studying apoptosis and for detection of estrogen receptor (ER alpha in luminal epithelium of the uterus and oviduct. Enzyme-linked immunosorbent assay was used for serum estradiol level determination. Nicotine in group B decreased estradiol level and ERalpha numbers both in the uterus and oviduct (p<0.05. Co-administration of melatonin-nicotine in Group D ameliorated the histology of the uterus and oviduct, increased ERalpha numbers and reduced apoptosis in the uterus and oviduct compared with the nicotine Group B (p<0.05. This study indicates that nicotine impairs the histology of the uterus and oviduct and co-administration of melatonin-nicotine ameliorates these findings, partly through alteration in ERalpha numbers and reduction of apoptosis

  1. Temporal Relationships Between Napping and Nocturnal Sleep in Healthy Adolescents.

    Science.gov (United States)

    Jakubowski, Karen P; Hall, Martica H; Lee, Laisze; Matthews, Karen A

    2017-01-01

    Many adolescents do not achieve the recommended 9 hr of sleep per night and report daytime napping, perhaps because it makes up for short nocturnal sleep. This article tests temporal relationships between daytime naps and nighttime sleep as measured by actigraphy and diary among 236 healthy high school students during one school week. Mixed model analyses adjusted for age, race, and gender demonstrated that shorter actigraphy-assessed nocturnal sleep duration predicted longer napping (measured by actigraphy and diary) the next day. Napping (by actigraphy and diary) predicted shorter nocturnal sleep duration and worse sleep efficiency that night measured by actigraphy. Diary-reported napping also predicted poorer self-reported sleep quality that night. Frequent napping may interfere with nocturnal sleep during adolescence.

  2. Accompanying therapy with melatonin at radiation therapy for uterine body cancer

    International Nuclear Information System (INIS)

    Prokhach, N.E.; Sorochan, P.P.; Gromakova, Yi.A.; Krugova, M.; Sukhyin, V.S.

    2011-01-01

    The results of treatment for uterine body cancer using post-operative radiation therapy (RT) accompanied by melatonin administration are analyzed. Accompanying therapy with melatonin limited negative RT influence on hematological and immune indices and prevented aggravation of quality of life.

  3. Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

    Science.gov (United States)

    Bouchlariotou, Sofia; Liakopoulos, Vassilios; Giannopoulou, Myrto; Arampatzis, Spyridon; Eleftheriadis, Theodoros; Mertens, Peter R; Zintzaras, Elias; Messinis, Ioannis E; Stefanidis, Ioannis

    2014-08-01

    Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, pcircadian BP rhythm status ascribed this finding exclusively to non-dippers (pcircadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

  4. Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence.

    Science.gov (United States)

    Yang, Fan; Yang, Lei; Li, Yuan; Yan, Gege; Feng, Chao; Liu, Tianyi; Gong, Rui; Yuan, Ye; Wang, Ning; Idiiatullina, Elina; Bikkuzin, Timur; Pavlov, Valentin; Li, Yang; Dong, Chaorun; Wang, Dawei; Cao, Yang; Han, Zhenbo; Zhang, Lai; Huang, Qi; Ding, Fengzhi; Bi, Zhengang; Cai, Benzhi

    2017-10-01

    Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Melatonin enhances cold tolerance in drought-primed wild-type and abscisic acid-deficient mutant barley.

    Science.gov (United States)

    Li, Xiangnan; Tan, Dun-Xian; Jiang, Dong; Liu, Fulai

    2016-10-01

    Melatonin is involved in multiple plant developmental processes and various stress responses. To explore the roles of melatonin played as well as its association with abscisic acid (ABA) in a process of drought priming-induced cold tolerance (DPICT), a wild-type barley and its ABA-deficient mutant Az34 counterpart were selected for comparison, in which the effects of melatonin application (either foliarly or rhizospherically) and/or drought priming on the cold tolerance of both types of barleys were systematically investigated. It was demonstrated that the early drought priming induced an increase of endogenous melatonin production, which is not ABA dependent. In addition, exogenously applied melatonin resulted in higher ABA concentration in the drought-primed plants than in the nonprimed plants when exposed to cold stress, indicating that ABA responded in a drought-dependent manner. The interplay of melatonin and ABA leads to plants maintaining better water status. Drought priming-induced melatonin accumulation enhanced the antioxidant capacity in both chloroplasts and mitochondria, which sustained the photosynthetic electron transport in photosynthetic apparatus of the plants under cold stress. These results suggest that the exogenous melatonin application enhances the DPICT by modulating subcellular antioxidant systems and ABA levels in barley. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Research progress on the role of melatonin and its receptors in animal reproduction: A comprehensive review.

    Science.gov (United States)

    Talpur, H S; Chandio, I B; Brohi, R D; Worku, T; Rehman, Z; Bhattarai, D; Ullah, F; JiaJia, L; Yang, L

    2018-04-16

    Melatonin and its receptors play a crucial role in the regulation of the animal reproductive process, primarily in follicular development. However, the role that melatonin performs in regulating hormones related with reproduction remains unclear. Melatonin and its receptors are present both in female and male animals' organs, such as ovaries, heart, brain and liver. Melatonin regulates ovarian actions and is a key mediator of reproductive actions. Melatonin has numerous effects on animal reproduction, such as protection of gametes and embryos, response to clock genes, immune-neuroendocrine, reconciliation of seasonal variations in immune function, and silence or blockage of genes. The growth ratio of reproductive illnesses in animals has raised a remarkable concern for the government, animal caretakers and farm managers. In order to resolve this challenging issue, it is very necessary to conduct state-of-the-art research on melatonin and its receptors because melatonin has considerable physiognomies. This review article presents a current contemporary research conducted by numerous researchers from the entire world on the role of melatonin and its receptors in animal reproduction, from the year 1985 to the year 2017. Furthermore, this review shows scientific research challenges related to melatonin receptors and their explanations based on the findings of 172 numerous research articles, and also represents significant proficiencies of melatonin in order to show enthusiastic study direction for animal reproduction researchers. © 2018 The Authors. Reproduction in Domestic Animals Published by Blackwell Verlag GmbH.

  7. Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

    Science.gov (United States)

    Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

    2006-10-01

    Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

  8. Effect of melatonin and time of administration on irradiation-induced damage to rat testes

    Directory of Open Access Journals (Sweden)

    G. Take

    2009-07-01

    Full Text Available The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol or melatonin administered 24 h before (10 mg/kg, immediately before (20 mg/kg and 24 h after irradiation (10 mg/kg, all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05. Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05. Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

  9. Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells.

    Science.gov (United States)

    González-Fernández, Bárbara; Sánchez, Diana I; Crespo, Irene; San-Miguel, Beatriz; Álvarez, Marcelino; Tuñón, María J; González-Gallego, Javier

    2017-03-01

    The sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) system is involved in different pathological processes, including fibrogenesis. Melatonin abrogates activation of hepatic stellate cells (HSCs) and attenuates different profibrogenic pathways in animal models of fibrosis, but it is unknown if protection associates with its inhibitory effect on the SphK1/S1P axis. Mice in treatment groups received carbon tetrachloride (CCl 4 ) 5 μL g -1 body wt i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg kg -1  day -1 i.p, beginning 2 weeks after the start of CCl 4 administration. At both 4 and 6 weeks following CCl 4 treatment, liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased significantly. S1P production, and expression of S1P receptor (S1PR)1, S1PR3 and acid sphingomyelinase (ASMase) were significantly elevated. However, there was a decreased expression of S1PR2 and S1P lyase (S1PL). Melatonin attenuated liver fibrosis, as shown by a significant inhibition of the expression of α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β and collagen (Col) Ι. Furthermore, melatonin inhibited S1P production, lowered expression of SphK1, S1PR1, SP1R3, and ASMase, and increased expression of S1PL. Melatonin induced a reversal of activated human HSCs cell line LX2, as evidenced by a reduction in α-SMA, TGF-β, and Col I expression. Melatonin-treated cells also exhibited an inhibition of the SphK1/S1P axis. Antifibrogenic effect of SphK1 inhibition was confirmed by treatment of LX2 cells with PF543. Abrogation of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in liver fibrogenesis. © 2016 BioFactors, 43(2):272-282, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  10. Effects of melatonin implantation during the slow period of cashmere ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of melatonin implantation during the slow period of cashmere growth on fibre production in Inner Mongolian cashmere goats. It was found that melatonin implantation had no effect on the growth rate of cashmere, except from February to March when the rate of treated goats ...

  11. Differences in ocular parameters between diurnal and nocturnal raptors.

    Science.gov (United States)

    Beckwith-Cohen, Billie; Horowitz, Igal; Bdolah-Abram, Tali; Lublin, Avishai; Ofri, Ron

    2015-01-01

    To establish and compare normal ocular parameters between and within diurnal and nocturnal raptor groups. Eighty-eight ophthalmically normal raptors of six nocturnal and 11 diurnal species were studied. Tear production was measured using Schirmer tear test (STT) and phenol red thread test (PRTT), and applanation tonometry was conducted. Ultrasonographic measurements of axial length (AL), mediolateral axis (ML), vitreous body (VB), and pecten length (PL) were recorded, and conjunctival cultures were obtained. A weak correlation (R = 0.312, P = 0.006) was found between PRTT and STT. Tear production was significantly lower in nocturnal species (P raptors were positive for mycology or bacteriology, either on culture or PCR. The most common infectious agent isolated was Staphylococcus spp. Phenol red thread test and STT are both valid methods to measure tear production; however, a separate baseline must be determined for each species using these methods, as the results of one method cannot be extrapolated to the other. Due to significant differences observed within diurnal and nocturnal species, it appears that a more intricate division should be used when comparing these parameters for raptors, and the classification of diurnal or nocturnal holds little significance in the baseline of these data. © 2013 American College of Veterinary Ophthalmologists.

  12. Effect of Using Melatonin Implants on Postpartum Reproductive Indices in Tigaia Sheep Breed

    Directory of Open Access Journals (Sweden)

    Ioan Padeanu

    2012-10-01

    Full Text Available Investigations were carried out in a commercial farm from Turnu, Arad County, on a number of 110 indigenous adultewes from the Tigaia breed. It is estimated by some authors that administration of subcutaneous melatonin implantsduring a period of 30 days, in lactating or dry ewes, would improve the reproductive performances in some sheepbreeds. Subcutaneous melatonin implants (Melovin were inserted to the ewes in doses of 18 mg. Current research,emphasized treated that from indigenous Tigaia breed, can be obtained superior reproduction indexes if the animalsare treated with melatonin implants with 35 days before the mating season, differences from the untreated groupbeing significantly (p<0.001. However, in sheep treated used melatonin implants, the lambing interval were reducedwith 40 to 50%. It seems that use of melatonin implants Melovin type near the beginning of normal breeding season,increases the reproductive performance of adult ewes from the Tigaia breed.

  13. Human MT2 melatonin receptor and its melatonin recognition site: a structural model

    Czech Academy of Sciences Publication Activity Database

    Luley, Ladislav; Stockner, T; Sovová, Žofie; Mazna, Petr; Ettrich, Rüdiger; Teisinger, Jan

    Roč.272, č.S1 (2005), s. 222-223 ISSN 1474-3833. [FEBS Congress /30./ and IUBMB Conference /9./. 02.07.2005-07.07.2005, Budapest] Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60870520 Keywords : melatonin receptor * model * structure Subject RIV: BO - Biophysics

  14. Melatonin improve the sperm quality in forced swimming test induced oxidative stress in nandrolone treated Wistar rats.

    Science.gov (United States)

    Minaii, Bagher; Moayeri, Ardeshir; Shokri, Saeed; Habibi Roudkenar, Mehryar; Golmohammadi, Taghi; Malek, Fatemeh; Barbarestani, Mohammad

    2014-01-01

    This study investigates the effects of melatonin on the sperm quality and testis weight after the combination of swimming exercise and nandrolone decanoate (DECA). Two groups of male Wistar rats were treated for eight weeks as follows; group A consist of CO (control), Sham, N (DECA), S (swimming) and NS (DECA plus swimming); and group B: Sham M (sham melatonin), M (melatonin), MN (melatonin plus DECA), MS (melatonin plus swimming), MNS (melatonin, DECA plus swimming). The motility of sperm was significantly improved in melatonin groups in comparison to N, S and NS groups (P≤0.05).  The left testes weight was decreased in N, NS and MNS groups, and the right testes weight was decreased in N,S,NS, MS and MNS groups in compare with the control group. This study concluded that melatonin probably could improve the sperm motility and sex organs weight after the combination of DECA and exercise.

  15. Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants

    Directory of Open Access Journals (Sweden)

    Hyoung-Yool Lee

    2017-10-01

    Full Text Available Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl2 or AlCl3 and monitored the structures of subcellular organelles—such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER—using confocal microscopic analysis. Unlike AlCl3 treatment, CdCl2 (0.5 mM treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm.

  16. Effect of exogenous melatonin and different photoperiods on oxidative status and antioxidant enzyme activity in Chhotanagpuri ewe.

    Science.gov (United States)

    Choudhary, Pankaj Kumar; Ishwar, Ajay Kumar; Kumar, Rajesh; Niyogi, Debasish; Kumar, Mukesh

    2018-02-01

    The present study was conducted to evaluate the effect of exogenous melatonin under different photoperiods on oxidative status in Chhotanagpuri ewe. A total of 42 non-pregnant, non-lactating Chhotanagpuri ewe, having body weight ranging between 14.11±0.09 and 15.38±0.06 kg, were selected and were isolated from rams 2 months before melatonin administration. The selected animals were allocated randomly into seven groups, namely, Group I (normal control), Group II (long day [LD] control), Group III (LD+melatonin administration orally, 3 mg/day), Group IV (LD+melatonin administration subcutaneously, 1 mg/day), Group V (short day [SD] control), Group VI (SD+melatonin administration orally, 3 mg/day), and Group VII (SD+melatonin administration subcutaneously, 1 mg/day) comprising six animals in each group. Rams were then introduced into each group after completion of exogenous administration of melatonin. Blood samples with anticoagulant in vials were collected from each animal day before the start of the experiment and thereafter every month up to 5 th month. Hemolysate was prepared for estimation of oxidative stress parameters such as malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). It was observed that the level of MDA was significantly (pexogenous administration of melatonin was significantly (pexogenous administration of melatonin, SOD concentration was significantly (pexogenous administration of melatonin, CAT concentration was significantly (pexogenous melatonin was able to reduce significantly the level of MDA and increased the activity of SOD and CAT in Chhotanagpuri ewe.

  17. [Role of melatonin in calcium overload-induced heart injury].

    Science.gov (United States)

    Kong, Lingheng; Wei, Ming; Sun, Na; Zhu, Juanxia; Su, Xingli

    2017-06-28

    To investigate the role of melatonin in calcium overload-induced heart injury.
 Methods: Thirty-two rats were divided into 4 groups: a control group (Control), a melatonin control group (Mel), a calcium overload group (CaP), and a calcium overload plus melatonin group (Mel+CaP). Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium. Lactate dehydrogenase (LDH) activity in the coronary flow was determined. The expressions of caspase-3 and cytochrome c were determined by Western blot. The pathological morphological changes in myocardial fiber were analyzed by HE staining.
 Results: Compared with the control group, calcium overload significantly induced an enlarged infarct size (Poverload-induced heart injury.

  18. Nocturnal Hypertension: Neglected Issue in Comprehensive Hypertension Management

    Directory of Open Access Journals (Sweden)

    Andi Kristanto

    2016-09-01

    Full Text Available The body circardian rhythm affects blood pressure variability at day and night, therefore blood pressure at day and night might be different. Nocturnal hypertension is defined as increase of blood pressure >120/70mmHg at night, which is caused by disturbed circadian rhythm, and associated with higher cardiovascular and cerebrovascular events also mortality in hypertensive patients. Nocturnal hypertension and declining blood pressure pattern, can only be detected by continuous examination for 24 hours, also known as ambulatory blood pressure measurement (ABPM. Chronotherapy, has become a strategy for managing the hypertensive nocturnal patients, by taking hypertensive medication at night to obtain normal blood pressure decrease in accordance with the normal circadian rhythm and, improving blood pressure control.

  19. Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm.

    Science.gov (United States)

    Tranquilli, A L; Turi, A; Giannubilo, S R; Garbati, E

    2004-03-01

    We assessed the correlation between the rhythm of melatonin concentration and circadian blood pressure patterns in normal and hypertensive pregnancy. Ambulatory 24-h blood pressure and blood samples every 4 h were monitored in 16 primigravidae who had shown an abnormal circadian blood pressure pattern (eight pre-eclamptic and eight normotensive) in pregnancy and 6-12 months after pregnancy. The circadian rhythm was analyzed by chronobiological measures. Eight normotensive women with maintained blood pressure rhythm served as controls. During pregnancy, melatonin concentration was significantly higher in pre-eclamptic than in normotensive women (pre-eclampsia, 29.4 +/- 1.9 pg/ml, normotensin, altered rhythm, 15.6 +/- 2.1; controls, 22.7 +/- 1.8; p lost in all pregnant women with loss of blood pressure rhythm. After pregnancy, normotensive women showed a reappearance of both melatonin and blood pressure rhythm, whereas pre-eclamptic women showed a reappearance of blood pressure but not melatonin rhythm. The loss of blood pressure rhythm in pregnancy is consistent with the loss of melatonin concentration rhythm. In pre-eclamptic women, the normalization of blood pressure rhythm, while melatonin rhythm remained altered, suggests a temporal or causal priority of circadian concentration of melatonin in the determination of blood pressure trend.

  20. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Hui Ming Chua

    2016-01-01

    Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

  1. Melatonin Inhibits Reactive Oxygen Species-Driven Proliferation, Epithelial-Mesenchymal Transition, and Vasculogenic Mimicry in Oral Cancer.

    Science.gov (United States)

    Liu, Rui; Wang, Hui-Li; Deng, Man-Jing; Wen, Xiu-Jie; Mo, Yuan-Yuan; Chen, Fa-Ming; Zou, Chun-Li; Duan, Wei-Feng; Li, Lei; Nie, Xin

    2018-01-01

    Globally, oral cancer is the most common type of head and neck cancers. Melatonin elicits inhibitory effects on oral cancer; however, the biological function of melatonin and underlying mechanisms remain largely unknown. In this study, we found that melatonin impaired the proliferation and apoptosis resistance of oral cancer cells by inactivating ROS-dependent Akt signaling, involving in downregulation of cyclin D1, PCNA, and Bcl-2 and upregulation of Bax. Melatonin inhibited the migration and invasion of oral cancer cells by repressing ROS-activated Akt signaling, implicating with the reduction of Snail and Vimentin and the enhancement of E-cadherin. Moreover, melatonin hampered vasculogenic mimicry of oral cancer cells through blockage of ROS-activated extracellular-regulated protein kinases (ERKs) and Akt pathways involving the hypoxia-inducible factor 1 α . Consistently, melatonin retarded tumorigenesis of oral cancer in vivo . Overall, these findings indicated that melatonin exerts antisurvival, antimotility, and antiangiogenesis effects on oral cancer partly by suppressing ROS-reliant Akt or ERK signaling.

  2. Melatonin controls seasonal breeding by a network of hypothalamic targets

    DEFF Research Database (Denmark)

    Revel, Florent G; Masson-Pévet, Mireille; Pévet, Paul

    2009-01-01

    In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible for the sea......In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible...... for the seasonal timing of reproduction, but the anatomical substrates and the cellular mechanisms through which melatonin modulates seasonal functions remain imprecise. Recently, several genes have been identified as being regulated by the photoperiod in the brain of seasonal mammals. These genes are thought....../GPR54 system and to the RFamide-related peptides.Interestingly, these systems involve different hypothalamic nuclei, suggesting that several brain loci may be crucial for melatonin to regulate reproduction, and thus represent key starting points to identify the long-sought-after mode and site...

  3. The anti-oxidant effects of melatonin derivatives on human gingival fibroblasts.

    Science.gov (United States)

    Phiphatwatcharaded, Chawapon; Puthongking, Ploenthip; Chaiyarit, Ponlatham; Johns, Nutjaree Pratheepawanit; Sakolchai, Sumon; Mahakunakorn, Pramote

    2017-07-01

    Aim of this in vitro study was to evaluate the anti-oxidant activity of indole ring modified melatonin derivatives as compared with melatonin in primary human gingival fibroblast (HGF) cells. Anti-oxidant activity of melatonin (MLT), acetyl-melatonin (AMLT) and benzoyl-melatonin (BMLT) was evaluated by5 standard methods as follows: 2, 2-diphenyl-1-picrylhydrazyl (DPPH); ferric ion reducing antioxidant power (FRAP); superoxide anion scavenging; nitric oxide (NO) scavenging; and thiobarbituric acid reactive substances (TBARs).Evaluation of cellular antioxidant activity (CAA) and protectivity against H 2 O 2 induced cellular damage was performed via MTT assay in HGF cells. According to the standard anti-oxidant assays, the antioxidant power of AMLT and BMLT were slightly less than MLT in FRAP and superoxide scavenging assays. In the NO scavenging and TBARs assays, BMLT and AMLT were more potent than MLT, whereas DPPH assays demonstrated that MLT was more potent than others. BMLT and AMLT had more potent anti-oxidant and protective activities against H 2 O 2 in HGF cells as compared with MLT. MLT derivatives demonstrated different anti-oxidant activities as compared with MLT, depending upon assays. These findings imply that N-indole substitution of MLT may help to improve hydrogen atom transfer to free radicals but electron transfer property is slightly decreased. Anti-oxidant and protective effects of melatonin derivatives (AMLT and BMLT) on human gingival fibroblasts imply the potential use of these molecules as alternative therapeutics for chronic inflammatory oral diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Is newborn melatonin production influenced by magnetic fields produced by incubators?

    Science.gov (United States)

    Bellieni, Carlo Valerio; Tei, Monica; Iacoponi, Francesca; Tataranno, Maria Luisa; Negro, Simona; Proietti, Fabrizio; Longini, Mariangela; Perrone, Serafina; Buonocore, Giuseppe

    2012-08-01

    During permanence in most incubators, newborns are very close to the electric engine, which represents a source of electromagnetic fields (EMF). Previous studies demonstrated a decrease in melatonin production in adults and animals exposed to EMF. To assess melatonin production in a group of newborns exposed to EMF, and to evaluate whether removing the babies from the source of MF can affect melatonin production. We have recruited 28 babies (study group), who had spent at least 48 h in incubator where we had previously assessed the presence of significant EMF. We have measured their mean 6-hydroxy-melatonin-sulfate (6OHMS) urine excretion at the end of their permanence in the incubators, and compared it with their mean 6OHMS excretion after having been put in cribs, where EMF are below the detectable limit (babies who were not exposed to EMF during both samples. Mean 6OHMS/cr values were respectively 5.34±4.6 and 7.68±5.1ng/mg (p=0.026) when babies were exposed to EMF in incubators, and after having been put in the crib. In the control group, mean 6OHMS/cr values in the first and in the second sample were respectively 5.91±5.41 vs 6.17±3.94ng/mg (p=0.679). The transitory increase in melatonin production soon after removing newborns from incubators demonstrates a possible influence of EMF on melatonin production in newborns. Further studies are needed to confirm these data. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Does the use of melatonin overcome drug resistance in cancer chemotherapy?

    Science.gov (United States)

    Asghari, Mohammad Hossein; Ghobadi, Emad; Moloudizargari, Milad; Fallah, Marjan; Abdollahi, Mohammad

    2018-03-01

    Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound. Reduced sensitivity and also resistance of cancer cells to antineoplastic agents are common events which might arise as a result of genomic instability of the malignant cells. Genetic mutations provide numerous mechanisms for these cells to resist cytotoxic therapies. Melatonin, due to its pleitropic effects, is able to correct these alterations in favour of sensitization to antineoplastic agents as evident by increased response to treatment via modulating the expression and phosphorylation status of drug targets, the reduced clearance of drugs by affecting their metabolism and transport within the body, decreased survival of malignant cells via altering DNA repair and telomerase activity, and enhanced responsiveness to cell death-associated mechanisms such as apoptosis and autophagy. These effects are presumably governed by melatonin's interventions in the main signal transduction pathways such as Akt and MAPK, independent of its antioxidant properties. Possessing such a signaling altering nature, melatonin can considerably affect the drug-resistance mechanisms employed by the malignant cells in breast, lung, hepatic, and colon cancers as well as different types of leukemia which are the subject of the current review. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Different Intensities of Treadmill Running Exercise do Not Alter Melatonin Levels in Rats

    Directory of Open Access Journals (Sweden)

    Ionara Rodrigues Siqueira

    2011-04-01

    Full Text Available Background: Regular and moderate exercise has been considered an interesting neuroprotective strategy. Our research group demonstrated that a protocol of moderate exercise on a treadmill reduced, while a protocol of high-intensity exercise increased in vitro ischemic cell damage in Wistar rats. The molecular mechanisms by which physical exercise exerts neuroprotective effects remain unclear. Accumulating evidence suggests that exercise may have short- and long-term effects on melatonin secretion in humans. Melatonin, the main product of the pineal gland, has been shown to have neuroprotective effects in models of brain and spinal cord injury and cerebral ischemia. A dual modulation of melatonin secretion by physical activity has also been demonstrated. This study aimed to investigate the effect of different exercise intensities, moderate- and high-intensity exercise, on serum melatonin levels in rats. Methods: Thirty-five adult male Wistar rats were divided into non-exercised (sedentary and exercised (20- or 60-min sessions groups. The exercise protocols consisted of two weeks of daily treadmill training. Blood samples were collected approximately 16 hours after the last training session (8:00-10:00 and melatonin levels were assayed by ELISA. Results: The exercise protocols, two weeks of 20 min/day or 60 min/day of treadmill running, did not affect serum melatonin levels. Conclusion: Our data demonstrated that melatonin levels may not be directly involved in the exercise-induced, intensity-dependent dual effect on in vitro ischemia.

  7. Changes in melatonin levels in transgenic 'Micro-Tom' tomato overexpressing ovine AANAT and ovine HIOMT genes.

    Science.gov (United States)

    Wang, Lin; Zhao, Yu; Reiter, Russel J; He, Changjiu; Liu, Guoshi; Lei, Qiong; Zuo, Bixiao; Zheng, Xiao Dong; Li, Qingtian; Kong, Jin

    2014-03-01

    In animals, the melatonin biosynthesis pathway has been well defined after the isolation and identification of the four key genes that are involved in the conversion of tryptophan to melatonin. In plants, there are special alternative catalyzing steps, and plant genes share very low homology with the animal genes. It was of interest to examine the phenotype of transgenic Micro-Tom tomato plants overexpressing the homologous sheep oAANAT and oHIOMT genes responsible for the last two steps of melatonin synthesis. The oAANAT transgenic plants have higher melatonin levels and lower indoleacetic acid (IAA) contents than control due to the competition for tryptophan, the same precursor for both melatonin and IAA. Therefore, the oAANAT lines lose the 'apical dominance' inferring that melatonin likely lacks auxin activity. The significantly higher melatonin content in oHIOMT lines than oAANAT lines provides new proof for the important role of ASMT in plant melatonin synthesis. In addition, the enhanced drought tolerance of oHIOMT lines will also be an important contribution for plant engineering. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Relationships between Salivary Melatonin Levels, Quality of Sleep, and Stress in Young Japanese Females

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ito

    2013-01-01

    Full Text Available A decrease in the quality of sleep is believed to cause anxiety and worsen depression. Comparisons of salivary melatonin levels with different factors including quality of sleep, state and trait anxieties, and depression, were conducted to examine whether there is a relationship between melatonin, presumably associated with sleep, and psychological stress. The saliva of healthy young females was collected during the daytime and before they went to bed at night (when they were awake and resting in a sitting position, and salivary melatonin levels were measured. The quality of sleep was scored using the Pittsburgh Sleep Quality Index (PSQI–-a questionnaire method. State and trait anxieties, and depression were scored using other questionnaire methods: the State-Trait Anxiety Inventory (STAI and Self-Rating Depression Scale (SDS, respectively. The following findings were obtained: (1 Salivary melatonin levels measured during the daytime and before going to bed were higher in females with a high depression score, compared to those with a low score, and there was a correlation between the depression scores and salivary melatonin levels measured at night; and (2 salivary melatonin levels measured before going to bed at night (in a sitting position were higher in females with a high state anxiety score, suggesting a correlation between state anxiety scores and salivary melatonin levels during the night. Both depression and a sense of anxiety are forms of psychological stress. Therefore, it is assumed that, when a person is under psychological stress, the action of melatonin as a ligand on its receptor is reduced. Meaning psychological stress may induce oxidative stress in the body. On the other hand, no correlation was noted between the quality of sleep and salivary melatonin levels during the night, presumably because saliva was collected when the subjects were awake and sitting, rather than sleeping.

  9. Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: implications for an ancient antioxidant system.

    Science.gov (United States)

    Manchester, L C; Poeggeler, B; Alvares, F L; Ogden, G B; Reiter, R J

    1995-01-01

    Rhodospirillum rubrum is a spiral anoxygenic photosynthetic bacterium that can exist under either aerobic or anaerobic conditions. The organism thrives in the presence of light or complete darkness and represents one of the oldest species of living organisms, possibly 2-3.5 billion years old. The success of this prokaryotic species may be attributed to the evolution of certain indole compounds that offer protection against life-threatening oxygen radicals produced by an evolutionary harsh environment. Melatonin, N-acetyl-5-methoxytryptamine, is an indolic highly conserved molecule that exists in protists, plants, and animals. This study was undertaken to determine the presence of an immunoreactive melatonin in the kingdom Monera and particularly in the photosynthetic bacterium, R. rubrum, under conditions of prolonged darkness or prolonged light. Immunoreactive melatonin was measured during both the extended day and extended night. Significantly more melatonin was observed during the scotophase than the photophase. This study marks the first demonstration of melatonin in a bacterium. The high level of melatonin observed in bacteria may provide on-site protection of bacterial DNA against free radical attack.

  10. A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2013-10-01

    Full Text Available Mariana G Figueiro, Andrew Bierman, Mark S ReaLighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USAAbstract: A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent “blue” versus “yellow” cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing “blue” responses, but not hyperpolarizing “yellow” responses, from the “blue” versus “yellow” pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of “blue” light, but not “yellow” light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1 2-second flashes of 111 W/m2 of blue (λmax ≈ 480 nm light once every minute for 1 hour, (2 131 W/m2 of green (λmax ≈ 527 nm light, continuously on for 1 hour, and (3 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our

  11. Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc.

    Science.gov (United States)

    Baltaci, Abdulkerim Kasım; Mogulkoc, Rasim

    2017-06-01

    Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT 3 , FT 4 , TT 3 , and TT 4 ) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.

  12. Plasma Melatonin Levels in Relation to the Light-Dark Cycle and Parental Background in Domestic Pigs

    Directory of Open Access Journals (Sweden)

    Andersson H

    2001-06-01

    Full Text Available To study porcine melatonin secretion in a stable environment 3 daytime (10.00 – 15.00 and 3 nighttime (22.00 – 03.00 plasma samples were collected by jugular venipuncture from 15 gilts, 16 sows, 3 boars and 48 piglets (24 females and 24 males from 8 litters and analysed for melatonin content. Nighttime melatonin concentrations were higher than daytime melatonin concentrations (p

  13. Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature

    NARCIS (Netherlands)

    Vural, Esmée M. S.; van Munster, Barbara C.; de Rooij, Sophia E.

    2014-01-01

    Melatonin is a hormone that regulates circadian rhythm, and its levels decline with age. As melatonin levels decrease, older adults are prone to develop disorders related to an altered circadian rhythm. The effective dose of melatonin supplementation in these disorders remains unclear. Our objective

  14. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

    Directory of Open Access Journals (Sweden)

    Cristian R. Astorga

    2018-03-01

    Full Text Available Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN, a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs.Methods: Twelve lambs (Ovis aries gestated and born at highlands (3,600 m were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1 during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations.Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05. This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05 and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05. Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05. Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05.Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

  15. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

    Science.gov (United States)

    Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

    2018-01-01

    Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

  16. Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis

    Science.gov (United States)

    Xu, Jianglin; Suri, Rita S.; Nesrallah, Gihad; Lindsay, Robert; Garg, Amit X.; Lester, Keith; Ofsthun, Norma; Lazarus, Michael; Hakim, Raymond M.

    2012-01-01

    Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during 2 years of follow-up in a 1:3 propensity score–matched cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis. Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61–0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score–matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials. PMID:22362905

  17. Desmopressin (melt) therapy in children with monosymptomatic nocturnal enuresis and nocturnal polyuria results in improved neuropsychological functioning and sleep.

    Science.gov (United States)

    Van Herzeele, Charlotte; Dhondt, Karlien; Roels, Sanne P; Raes, Ann; Hoebeke, Piet; Groen, Luitzen-Albert; Vande Walle, Johan

    2016-09-01

    There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. The aim of this study was to investigate whether a decrease in nocturnal diuresis volume not only improves enuresis but also ameliorates disrupted sleep and (neuro)psychological dysfunction, the major comorbidities of this disorder. In this open-label, prospective phase IV study, 30 children with monosymptomatic nocturnal enuresis (MNE) underwent standardized video-polysomnographic testing and multi-informant (neuro)psychological testing at baseline and 6 months after the start of desmopressin treatment in the University Hospital Ghent, Belgium. Primary endpoints were the effect on sleep and (neuro)psychological functioning. The secondary endpoint was the change in the first undisturbed sleep period or the time to the first void. Thirty children aged between 6 and 16 (mean 10.43, standard deviation 3.08) years completed the study. The results demonstrated a significant decrease in periodic limb movements during sleep (PLMS) and a prolonged first undisturbed sleep period. Additionally, (neuro)psychological functioning was improved on several domains. The study demonstrates that the degree of comorbidity symptoms is at least aggravated by enuresis (and/or high nocturnal diuresis rate) since sleep and (neuro)psychological functioning were significantly ameliorated by treatment of enuresis. These results indicate that enuresis is not such a benign condition as has previously been assumed.

  18. Direct fluorination of melatonin and 5-hydroxy-L-tryptophan with [18F]F2

    International Nuclear Information System (INIS)

    Chirakal, R.; Firnau, G.; Garnett, E.S.

    1986-01-01

    In order that melatonin receptors may be studied in man with positron emission tomography, melatonin labelled with a positron emitting isotope is needed. The preparation of 6-fluoro-melatonin labelled with F-18 is described. Using the same fluorination method, 5-hydroxy-6-(F-18)fluorotryptophan and 4-(F-18)fluoro-5-hydroxy-tryptophan were also prepared. (UK)

  19. Production and purification of polyclonal antibody against melatonin hormone

    Directory of Open Access Journals (Sweden)

    Fooladsaz K

    1999-09-01

    Full Text Available Nowadays immunochemical techniques have played a very important and valuable role in quantitative and qualitative assays of liquid compounds of the body. Producing antibody against immunogenes is the first step to make immunochemical kits. In this study production and purification of polyclonal antibody against melatonin has been considered. This hormone which has several important functions in physiological conditions such as migraine, cirrhosis, mammary gland cancer and other diseases, is the most important pineal gland secretion. This gland is a circumventricular organ of brain and according to histological and anatomical studies, it is a high secretory organ, that secretes active biological substances like melatonin, oxytocin, serotonin and ect. In this study, melatonin has been considered as hapten and has become an immunogen by being linked to the bovine serum Albumin. Then, by the immunization of three white New Zeland rabbits that had the booster injections in regular intervals, the antibody titer was detected to be 1/2000, by using checkboard curves, and with the use of melatonin linked to penicillinase as a labeled antigen, the titer was detected 1/200. Finally an antibody with high purification rate has been obtained, which can be used in immunochemical assays like RIA, ELISA, and EIA.

  20. Melatonin, Noncoding RNAs, Messenger RNA Stability and Epigenetics—Evidence, Hints, Gaps and Perspectives

    Science.gov (United States)

    Hardeland, Rüdiger

    2014-01-01

    Melatonin is a highly pleiotropic regulator molecule, which influences numerous functions in almost every organ and, thus, up- or down-regulates many genes, frequently in a circadian manner. Our understanding of the mechanisms controlling gene expression is actually now expanding to a previously unforeseen extent. In addition to classic actions of transcription factors, gene expression is induced, suppressed or modulated by a number of RNAs and proteins, such as miRNAs, lncRNAs, piRNAs, antisense transcripts, deadenylases, DNA methyltransferases, histone methylation complexes, histone demethylases, histone acetyltransferases and histone deacetylases. Direct or indirect evidence for involvement of melatonin in this network of players has originated in different fields, including studies on central and peripheral circadian oscillators, shift work, cancer, inflammation, oxidative stress, aging, energy expenditure/obesity, diabetes type 2, neuropsychiatric disorders, and neurogenesis. Some of the novel modulators have also been shown to participate in the control of melatonin biosynthesis and melatonin receptor expression. Future work will need to augment the body of evidence on direct epigenetic actions of melatonin and to systematically investigate its role within the network of oscillating epigenetic factors. Moreover, it will be necessary to discriminate between effects observed under conditions of well-operating and deregulated circadian clocks, and to explore the possibilities of correcting epigenetic malprogramming by melatonin. PMID:25310649