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.

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.

The analgesic effects of exogenous melatonin in humans.

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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

[Morpho-functional reaction of spleen natural killer cells and macrophages to melatonin administration to the animals kept on different illumination regimens].

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Shatskikh, O A; Luzikova, E M

2012-01-01

The aim this investigation was to study the changes in the numbers of spleen CD57+ and CD68+ cells (natural killer cells and macrophages respectively) after melatonin administration to the animals kept on different illumination regimens. The experimental animals were given melatonin in dose of 0.03 mg per day for 2 and 4 weeks under conditions of natural illumination or artificial darkening. Spleen paraffin sections were stained using immunohistochemical methods for detection of CD57+ and CD68+ cells. It was shown that long-term administration of melatonin under conditions of natural illumination had an immunosuppressive effect, that was manifested by the depopulation of the marginal zones, white pulp and all the zones of the red pulp, parenchyma loosening and denudation of the reticular stroma of the organ. However, long-term hormone administration under conditions of artificial darkening had an immunostimulatory effect as evidenced by the increased inflow of immunocompetent cells into the spleen, their migration from the white pulp into the marginal zones and emigration into peripheral blood flow, concomitant with the increase in the number of lymphoid nodules. The number of CD57+ and CD68+ cells was increased in splenic periarterial lymphoid sheaths and decreased in B-dependent zones of the organ.

Study of Melatonin Protective Effects on Learning and Memory Deficits Induced by Administration of Lead during Pregnancy and Postpartum in Rat: Behavioral and Biochemical Evaluations

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Elham Soleimani

2016-05-01

Full Text Available Abstract Background: Few studies have investigated the possible ways to prevent lead induced defects during gestation and lactation. The aim of this study was to investigate the effect of melatonin as a hormone with antioxidant properties on oxidative stress in the hippocampus and learning and memory impairment induced by administration of lead. Materials and Methods: Pregnant rats were exposed to treatments of control, lead acetate (0.2% solution in water, lead acetate + melatonin and melatonin (10 mg / kg by oral gavage from gestation day 6 until weaning. 21 days after birth, the activities of several antioxidant enzymes including superoxide dismutase (SOD, glutathione peroxidase (GPX and catalase (CAT as well as malondialdehyde levels in hippocampus of 23 male offspring rats were assayed. To behavioral studies, on postnatal day 30, 57 rats were trained 6 days in the Morris water maze and the probe test was performed 24 h later. Results: The results showed that administration of lead during pregnancy and lactation could increase MDA levels and decrease glutathione peroxidase, superoxide dismutase and catalase antioxidant enzymes activities in the hippocampus of male offspring. Also, this treatment significantly disrupted performance of the Morris water maze test and impaired learning and spatial memory in male offspring compared with control. Administration of melatonin attenuated lipid peroxidation and could improve learning and spatial memory deficits and the activity of antioxidant enzymes in lead exposure group. Conclusion: Melatonin as a neuropotective drug can protect the hippocampus against the complications of lead exposure, in the course of development.

The role of melatonin as an antioxidant in the follicle

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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.

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.

Melatonin in perioperative medicine: Current perspective

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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.

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...

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

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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.

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

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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.

Melatonin for the treatment of irritable bowel syndrome.

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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.

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

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.

Melatonin Promotes Superovulation in Sika Deer (Cervus nippon

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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.

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

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 ...

Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

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M. Kassayová

2007-01-01

Full Text Available The aim of this study was to evaluate the effect of melatonin (MEL on N-methyl-N-nitrosourea (NMU-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20. Immobilization (2 h per day began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21% when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.

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...

Melatonin attenuates thiocyanate-induced vasoconstriction in aortic rings

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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

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.

Dietary intake, growth and development of children with ADHD in a randomized clinical trial of Ritalin and Melatonin co-administration: Through circadian cycle modification or appetite enhancement?

Science.gov (United States)

Mostafavi, Seyed-Ali; Mohammadi, Mohammad Reza; Hosseinzadeh, Payam; Eshraghian, Mohammad Reza; Akhondzadeh, Shahin; Hosseinzadeh-Attar, Mohammad Javad; Ranjbar, Elham; Kooshesh, Seyed Mohammad-Ali; Keshavarz, Seyed-Ali

2012-01-01

It is postulated that ritalin may adversely affect sleep, appetite, weight and growth of some children with ADHD. Therefore, we aimed to evaluate melatonin supplementation effects on dietary intake, growth and development of children with ADHD treated with ritalin through circadian cycle modification and appetite mechanisms. After obtaining consent from parents, 50 children aged 7-12 with combined form of AD/HD were randomly divided into two groups based on gender blocks: one received melatonin (3 or 6 mg based on weight) combined with ritalin (1mg/kg) and the other took placebo combined with ritalin (1mg/kg) in a double blind randomized clinical trial. Three-day food record, and standard weight and height of children were evaluated prior to the treatment and 8 weeks after the treatment. Children's appetite and sleep were evaluated in weeks 0, 2, 4 and 8. Hypotheses were then analyzed using SPSS17. Paired sample t-test showed significant changes in sleep latency (23.15±15.25 vs. 17.96±11.66; p=0.047) and total sleep disturbance score (48.84±13.42 vs. 41.30±9.67; p=0.000) before and after melatonin administration, respectively. However, appetite and food intake did not change significantly during the study. Sleep duration and appetite were significantly correlated in melatonin group (Pearson r=0.971, p=0.029). Mean height (138.28±16.24 vs. 141.35±16.78; P=0.000) and weight (36.73±17.82 vs. 38.97±17.93; P=0.005) were significantly increased in melatonin treated children before and after the trial. Administration of melatonin along with ritalin improves height and weight growth of children. These effects may be attributed to circadian cycle modification, increasing sleep duration and the consequent more growth hormone release during sleep.

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

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.

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

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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.

Metabolic syndrome, its pathophysiology and the role of melatonin.

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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.

Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study.

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Tagliaferri, Valeria; Romualdi, Daniela; Scarinci, Elisa; Cicco, Simona De; Florio, Christian Di; Immediata, Valentina; Tropea, Anna; Santarsiero, Carla Mariaflavia; Lanzone, Antonio; Apa, Rosanna

2018-02-01

The objective of the study was to investigate the effects of 6 months of melatonin administration on clinical, endocrine, and metabolic features of women affected by polycystic ovary syndrome (PCOS). This is a prospective cohort study including 40 normal-weight women with PCOS between January and September 2016, enrolled in an academic research environment. Ultrasonographic pelvic examinations, hirsutism score evaluation, hormonal profile assays, oral glucose tolerance test, and lipid profile at baseline and after 6 months of melatonin administration were performed. Melatonin treatment significantly decreased androgens levels (free androgen index: P < .05; testosterone: P < .01; 17 hydroxyprogesterone: P < .01). Follicle-stimulating hormone levels significantly raised ( P < .01), and anti-Mullerian hormone serum levels significantly dropped after 6 months of melatonin treatment ( P < .01). No significant changes occurred in glucoinsulinemic and lipid parameters after treatment except a significant decrease of low-density lipoprotein cholesterol. Almost 95% of participants experienced an amelioration of menstrual cycles. Until now, only few data have been published about the role of melatonin in women with PCOS. This is the first study focused on the effects of exogenous oral melatonin administration on the clinical, endocrine, and metabolic characteristics of patients with PCOS. After 6 months of treatment, melatonin seems to improve menstrual irregularities and biochemical hyperandrogenism in women with PCOS through a direct, insulin-independent effect on the ovary. Based on our results, melatonin could be considered a potential future therapeutic agent for women affected by PCOS.

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

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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

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

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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.

Melatonin for women in pregnancy for neuroprotection of the fetus.

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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

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.  

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

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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.

Melatonin plays a protective role in postburn rodent gut pathophysiology.

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

2010-05-17

supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 micromole/kg) significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation.

Melatonin protects uterus and oviduct exposed to nicotine in mice

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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

Dietary intake, growth and development of children with ADHD in a randomized clinical trial of Ritalin and Melatonin co-administration: Through circadian cycle modification or appetite enhancement?

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Seyed-Ali Mostafavi

2012-09-01

Full Text Available Objective: It is postulated that ritalin may adversely affect sleep, appetite, weight and growth of some children with ADHD. Therefore, we aimed to evaluate melatonin supplementation effects on dietary intake, growth and development of children with ADHD treated with ritalin through circadian cycle modification and appetite mechanisms.Method: After obtaining consent from parents, 50 children aged 7-12 with combined form of AD/HD were randomly divided into two groups based on gender blocks: one received melatonin (3 or 6 mg based on weight combined with ritalin (1mg/kg and the other took placebo combined with ritalin (1mg/kg in a double blind randomized clinical trial. Three-day food record, and standard weight and height of children were evaluated prior to the treatment and 8 weeks after the treatment. Children’s appetite and sleep were evaluated in weeks 0, 2, 4 and 8. Hypotheses were then analyzed using SPSS17.Results: Paired sample t-test showed significant changes in sleep latency (23.15±15.25 vs. 17.96±11.66; p=0.047 and total sleep disturbance score (48.84±13.42 vs. 41.30±9.67; p=0.000 before and after melatonin administration, respectively. However, appetite and food intake did not change significantly during the study. Sleep duration and appetite were significantly correlated in melatonin group (Pearson r=0.971, p=0.029. Mean height (138.28±16.24 vs. 141.35±16.78; P=0.000 and weight (36.73±17.82 vs. 38.97±17.93; P=0.005 were significantly increased in melatonin treated children before and after the trial.Conclusion: Administration of melatonin along with ritalin improves height and weight growth of children. These effects may be attributed to circadian cycle modification, increasing sleep duration and the consequent more growth hormone release during sleep.

Effect of melatonin on sleep disorders in a monkey model of Parkinson's disease.

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Belaid, Hayat; Adrien, Joelle; Karachi, Carine; Hirsch, Etienne C; François, Chantal

2015-10-01

To evaluate and compare the effects of melatonin and levodopa (L-dopa) on sleep disorders in a monkey model of Parkinson's disease. The daytime and nighttime sleep patterns of four macaques that were rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were recorded using polysomnography in four conditions: at baseline, during the parkinsonian condition; after administration of L-dopa, and after administration of a combination of melatonin with L-dopa. It was confirmed that MPTP intoxication induces sleep disorders, with sleep episodes during daytime and sleep fragmentation at nighttime. L-dopa treatment significantly reduced the awake time during the night and tended to improve all other sleep parameters, albeit not significantly. In comparison to the parkinsonian condition, combined treatment with melatonin and L-dopa significantly increased total sleep time and sleep efficiency, and reduced the time spent awake during the night in all animals. A significant decrease in sleep latencies was also observed in three out of four animals. Compared with L-dopa alone, combined treatment with melatonin and L-dopa significantly improved all these sleep parameters in two animals. On the other hand, combined treatment had no effect on sleep architecture and daytime sleep. These data demonstrated, for the first time, objective improvement on sleep parameters of melatonin treatment in MPTP-intoxicated monkeys, showing that melatonin treatment has a real therapeutic potential to treat sleep disturbances in people with Parkinson's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

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Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

2017-02-01

The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

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Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

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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.

Maternal melatonin administration mitigates coronary stiffness and endothelial dysfunction, and improves heart resilience to insult in growth restricted lambs.

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Tare, Marianne; Parkington, Helena C; Wallace, Euan M; Sutherland, Amy E; Lim, Rebecca; Yawno, Tamara; Coleman, Harold A; Jenkin, Graham; Miller, Suzanne L

2014-06-15

Intrauterine growth restriction (IUGR) is associated with impaired cardiac function in childhood and is linked to short- and long-term morbidities. Placental dysfunction underlies most IUGR, and causes fetal oxidative stress which may impact on cardiac development. Accordingly, we investigated whether antenatal melatonin treatment, which possesses antioxidant properties, may afford cardiovascular protection in these vulnerable fetuses. IUGR was induced in sheep fetuses using single umbilical artery ligation on day 105-110 of pregnancy (term 147). Study 1: melatonin (2 mg h(-1)) was administered i.v. to ewes on days 5 and 6 after surgery. On day 7 fetal heart function was assessed using a Langendorff apparatus. Study 2: a lower dose of melatonin (0.25 mg h(-1)) was administered continuously following IUGR induction and the ewes gave birth normally at term. Lambs were killed when 24 h old and coronary vessels studied. Melatonin significantly improved fetal oxygenation in vivo. Contractile function in the right ventricle and coronary flow were enhanced by melatonin. Ischaemia-reperfusion-induced infarct area was 3-fold greater in IUGR hearts than in controls and this increase was prevented by melatonin. In isolated neonatal coronary arteries, endothelium-dependent nitric oxide (NO) bioavailability was reduced in IUGR, and was rescued by modest melatonin treatment. Melatonin exposure also induced the emergence of an indomethacin-sensitive vasodilation. IUGR caused marked stiffening of the coronary artery and this was prevented by melatonin. Maternal melatonin treatment reduces fetal hypoxaemia, improves heart function and coronary blood flow and rescues cardio-coronary deficit induced by IUGR. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Trials of bright light exposure and melatonin administration in a patient with non-24 hour sleep-wake syndrome.

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Hayakawa, T; Kamei, Y; Urata, J; Shibui, K; Ozaki, S; Uchiyama, M; Okawa, M

1998-04-01

We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running sleep-wake cycle was successfully treated with both scheduled bright light exposure and melatonin treatment. In the present study, morning bright light as well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm. Both these procedures achieved appropriate entrainment to a 24 h day. However, the patient did not continue morning bright light therapy after the discharge. Rising at appropriate times in the morning for bright light therapy was difficult for him to continue. Melatonin treatment was better tolerated because of its ease of application.

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

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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.

Effects of Melatonin on the Cerebellum of Infant Rat Following Kaolin-Induced Hydrocephalus: a Histochemical and Immunohistochemical Study.

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Uyanıkgil, Yiğit; Turgut, Mehmet; Baka, Meral

2017-02-01

Hydrocephalus is a developmental disorder causing abnormally collected cerebrospinal fluid within the cerebral ventricles. It leads to bigger skulls and many dysfunctions related to the nervous system. Here, we addressed whether exogenous melatonin administration could reverse the clinical features of kaolin-induced hydrocephalus in infantile rats. A controlled double-blinded study was conducted in 2-week-old 45 Wistar albino rats, which were divided into three groups: Group A, the control group, received intracisternal sham injection with solely the needle insertion; group B, the hydrocephalus group, was treated with isotonic NaCl after kaolin injection; and group C, the hydrocephalus + melatonin group, was given i.p. exogenous melatonin at a dose of 0.5 mg/100 g body weight after kaolin injection. Histological and immunohistochemical analyses were performed after the induction of hydrocephalus and melatonin administration. Glial fibrillary acidic protein was stained by immunohistochemical method. TUNEL method was used to define and quantitate apoptosis in the cerebellar tissues. Statistical analysis was performed by nonparametric Kruskal-Wallis H test, and once significance was determined among means, post hoc pairwise comparisons were carried out using Mann-Whitney U test. We found that melatonin administration significantly ameliorated ratio of substantia grisea area/substantia alba area in the cerebellum of infantile rats. Histologically, there was a significant reduction in the number of cerebellar apoptotic cells after the hydrocephalus induced by kaolin (P cerebellum were reversed by systemic melatonin administration in infantile rats with kaolin-induced hydrocephalus. Nevertheless, further studies are needed to suggest melatonin as a candidate protective drug in children with hydrocephalus.

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

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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

Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

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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

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

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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.

Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

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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.

Melatonin.

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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.

Metabolic Effects of Prolonged Melatonin Administration and Short-Term Fasting in Laboratory Rats

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B. Bojková

2006-01-01

Full Text Available The aim of this work was to evaluate the effect of prolonged administration of the pineal hormone melatonin and short-term fasting on metabolic variables in male and female Wistar:Han rats. Melatonin (MEL, 4 μg/ml of tap water was administered daily since the 5th week of age. The control group drank tap water. Rats were fed a standard type of diet ad libitum and were kept in the light regimen L:D - 12:12 h. The experiment was terminated after 11 (variant B or 12 (variant A weeks of MEL administration. The animals were sacrificed by quick decapitation following overnight fasting (variant A or 48-h fasting (variant B. Selected organs and tissues were removed and weighed and selected metabolic variables in the serum and tissues were determined. MEL decreased body mass independent of food and water intake in both sexes. In males (variant A MEL increased the weight of the heart muscle, spleen and adrenals; it decreased the absolute weight of epididymal fat and increased serum corticosterone and phospholipids concentration in comparison with controls. In females, serum glucose decrease and liver triacylglycerols increase were found. After 48-h fasting (variant B liver, spleen and adrenal weight increase in MELdrinking females was found. In males MEL increased the thymus weight and decreased the epididymal fat weight. In both sexes MEL increased serum corticosterone and liver glycogen concentration; MEL increased serum glucose in males and serum cholesterol concentration in females. Changes in the evaluated variables were also related to fasting duration prior to decapitation. A 48-h fasting at the end of the prolonged MEL intake (variant B vs. A decreased the absolute liver weight in both sexes and the epididymal/periovarial fat weight, and increased thymus weight in males. In females it decreased the absolute heart muscle weight and increased the spleen weight. In males, 48-h fasting increased serum corticosterone and phospholipids concentration; it

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

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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.

A role for melatonin in maintaining the pro- and anti-inflammatory balance by influencing leukocyte migration and apoptosis in carp

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Kepka, M.; Szwejser, E.; Pijanowski, L.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

2015-01-01

Melatonin is responsible for the synchronization of many physiological processes, including the immune response. Here we focus on the expression of melatonin MT1 receptors in/on leukocytes, and on the effects of melatonin administration on the inflammatory processes of carp. For the first time, we

Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats.

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Ríos-Lugo, María J; Jiménez-Ortega, Vanesa; Cano-Barquilla, Pilar; Mateos, Pilar Fernández; Spinedi, Eduardo J; Cardinali, Daniel P; Esquifino, Ana I

2015-03-01

Previous studies indicate that the administration of melatonin caused body weight and abdominal visceral fat reductions in rodent models of hyperadiposity. The objective of the present study performed in high-fat fed rats was to evaluate the activity of melatonin on gene expression of some medial basal hypothalamus (MBH) signals involved in feeding behavior regulation, including neuropeptide Y (NPY), proopiomelanocortin (POMC), prolactin-releasing peptide (PrRP), leptin- and insulin-receptors (R) and insulin-R substrate (IRS)-1 and -2. Blood levels of leptin and adiponectin were also measured. Adult Wistar male rats were divided into four groups (n=16 per group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet+melatonin; (iv) control diet+melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions: (a) tap water; (b) 25 μg/mL of melatonin. After 10 weeks, the high-fat fed rats showed augmented MBH mRNA levels of NPY, leptin-R, PrRP, insulin-R, IRS-1 and IRS-2. The concomitant administration of melatonin counteracted this increase. Feeding of rats with a high-fat diet augmented expression of the MBH POMC gene through an effect insensitive to melatonin treatment. The augmented levels of circulating leptin and adiponectin seen in high-fat fed rats were counteracted by melatonin as was the augmented body weight: melatonin significantly attenuated a body weight increase in high-fat fed rats without affecting chow or water consumption. Melatonin augmented plasma leptin and adiponectin in control rats. The results indicate that an effect on gene expression of feeding behavior signals at the central nervous system (CNS) may complement a peripheral rise of the energy expenditure produced by melatonin to decrease body weight in high-fat fed rats.

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)

Melatonin: functions and ligands.

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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.

Effect of Using Melatonin Implants on Postpartum Reproductive Indices in Tigaia Sheep Breed

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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.

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

OpenAIRE

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

2017-01-01

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 mic...

Circadian Variation in the Response to Experimental Endotoxemia and Modulatory Effects of Exogenous Melatonin

DEFF Research Database (Denmark)

Alamili, Mahdi; Klein, Mads; Lykkesfeldt, Jens

2013-01-01

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we...... investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5 mg/kg), LPS + melatonin (1 mg/kg), or LPS...

Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

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Mohammadreza Gholami

2014-02-01

Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion-Detorsion Model.

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Semercioz, Atilla; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim; Avunduk, Mustafa Cihat

2017-12-01

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion-detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia-reperfusion; 4. Zinc + ischemia-reperfusion; 5. Melatonin + ischemia-reperfusion; 6. Zinc + melatonin + ischemia-reperfusion. Zinc and melatonin were administered before ischemia-reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion-detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia-reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.

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

Involvement of Melatonin in Changing Depression-Like and Aggressive Behaviour in Rats Under Moderate Electromagnetic Shielding

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Temuryants, N. A.; Tumanyants, K. N.; Khusainov, D. R.; Cheretaev, I. V.; Tumanyants, E. N.

2017-12-01

It was found that moderate electromagnetic shielding, which attenuates constant and variable components of the geomagnetic field (19 h per day for 10 days), induces in male rats the development of depression-like behavior. This behavior is diagnosed on the basis of increased passive swimming time and a decreased duration of active swimming in the Porsolt test. These behaviors reach their peak on days 3-4 of the experiment. The daily administration of 1 mg/kg exogenous melatonin reduces these depression-like behaviors as soon as day 1 of the experiment, and this effect persists throughout all stages of the experiment. Electromagnetic shielding and the administration of 1 mg/kg exogenous melatonin do not change the levels of intraspecies aggressiveness. An increase in melatonin dosage to 5 mg/kg even further reduces depression-like symptoms and stops the increase in intraspecies aggressiveness during the experiment. The conclusion is made that melatonin plays an important role in the mechanisms of physiological effects of a weakened electromagnetic geomagnetic field.

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.

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

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine.

Science.gov (United States)

Guney, Y; Hicsonmez, A; Uluoglu, C; Guney, H Z; Ozel Turkcu, U; Take, G; Yucel, B; Caglar, G; Bilgihan, A; Erdogan, D; Nalca Andrieu, M; Kurtman, C; Zengil, H

2007-10-01

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

Directory of Open Access Journals (Sweden)

Y. Guney

2007-10-01

Full Text Available We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB or abdominopelvic (AP irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset or evening (activity span - 13 h after light onset. Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively to the irradiated rats. AP (P < 0.05 and TB (P < 0.05 irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS levels. Melatonin treatment in the morning (P < 0.05 or evening (P < 0.05 decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05. Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction.

Science.gov (United States)

Miller, Suzanne L; Yawno, Tamara; Alers, Nicole O; Castillo-Melendez, Margie; Supramaniam, Veena G; VanZyl, Niel; Sabaretnam, Tharani; Loose, Jan M; Drummond, Grant R; Walker, David W; Jenkin, Graham; Wallace, Euan M

2014-04-01

Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Melatonin: Buffering the Immune System

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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.

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

Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

Science.gov (United States)

Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

2004-02-01

There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

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.

The effects of exogenous melatonin on the morphology of thyrocytes in pinealectomized and irradiated rats

International Nuclear Information System (INIS)

Kundurovic, Z.; Sofic, E.

2006-01-01

We investigated the effects of exogenous melatonin on the thyrocytes morphology in gamma-irradiated rats under condition where the pineal gland, as a main physiological source of endogenous melatonin, was removed. Three months after pinealectomy animals were divided into two groups: one group of animals was treated with 0.5 ml of vehicle (ethanol diluted in water) and other group was injected intraperitoneally 2 mg/kg of melatonin dissolved in 0.5 ml of vehicle daily during the period of fourteen days. After this treatment all the animals were irradiated with a single dose of 8 Gy gamma rays. Ionising radiation induced apoptosis, hydropic swelling or/and necrosis in both groups of animals, however these changes were less discerned in the thyrocytes of melatonin-treated animals. Our findings demonstrate that administration of exogenous melatonin prior to irradiation reduces radiation-induced thyrocytes damage. (author)

Melatonin: the dark force.

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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.

Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

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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.

Melatonin Receptor Genes in Vertebrates

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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.

Melatonin labeled with hydrogen isotopes

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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)

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

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

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

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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.

Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles.

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Jang, Hoon; Na, Younghwa; Hong, Kwonho; Lee, Sangho; Moon, Sohyeon; Cho, Minha; Park, Miseon; Lee, Ok-Hee; Chang, Eun Mi; Lee, Dong Ryul; Ko, Jung Jae; Lee, Woo Sik; Choi, Youngsok

2017-10-01

Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27 Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27 Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: A randomized, double-blind, placebo-controlled trial.

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Hernández-Velázquez, B; Camara-Lemarroy, C R; González-González, J A; García-Compean, D; Monreal-Robles, R; Cordero-Pérez, P; Muñoz-Espinosa, L E

2016-01-01

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an acute inflammatory response and melatonin has a variety of immunomodulatory and antioxidant effects studied experimentally in pancreatobiliary pathology. The aim of our study was to evaluate the effects of peri-procedural administration of melatonin on the inflammatory response and lipid peroxidation associated with ERCP. In this proof-of-concept clinical trial, 37 patients with a high probability of choledocholithiasis were randomized to receive peri-procedure (ERCP) melatonin or placebo. We measured the serum concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), lipid peroxidation, amylase, and liver function tests 24h before and after the procedure. We found no pre-procedure or post-procedure differences between the melatonin group or the placebo group (P>.05) in the serum concentrations of TNF-alpha (melatonin: 153.8 vs. 149.4ng/m; placebo: 103.5 vs. 107.3ng/ml), IL-6 (melatonin: 131.8 vs. 133.3ng/ml; placebo: 177.8 vs. 197.8ng/ml), or VEGF (melatonin: 157.3 vs. 157.8pg/ml; placebo: 97.3 vs. 97.8pg/ml), or in relation to lipid peroxidation (melatonin: 39.2 vs. 72.3μg/ml; placebo: 66.4 vs. 90.5μg/ml). After ERCP, a significant decrease in the AST, ALT, and total bilirubin levels was found only in the melatonin group (P<.05). The administration of melatonin was safe and tolerable. Melatonin is safe and tolerable in patients undergoing ERCP, but it does not appear to affect inflammatory cytokine concentrations or lipid peroxidation. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

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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.

Influence of photoperiods on glycemic and adrenal catecholaminergic responses to melatonin administrations in adult male roseringed parakeets, Psittacula krameri Neumann.

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Maitra, S K; Dey, M; Dey, R; Bhattacharya, S; Sengupta, A

2000-11-01

Effects of daily (one hour prior to onset of darkness) injection of melatonin (25 micrograms/100 g body wt. for 30 days) on concentrations of blood glucose and adrenal catecholamines were studied in adult male roseringed parakeets, P. krameri under both natural (NP; about 12L:12D) and artificial long (LP; 16L:8D; lights were available in between 0600 and 2200 hrs) or short (SP; 8L:16D; lights were available between 0600 and 1400 hrs) photoperiodic conditions. The results indicate that neither LP, nor SP as such exerts any significant effect on blood glucose titre of control (vehicle of hormone administered) birds. Treatment with melatonin, however, induced hyperglycemia in both NP and LP bird groups, but hypoglycemia in SP birds. Unlike glycemic levels, amount of epinephrine (E) and norepinephrine (NE) in adrenals of control birds exhibited significant changes under altered photoperiods. A decrease in E and an increase in NE were noted in adrenals of both LP and SP birds. Exogenous melatonin in NP birds also caused a decrease in E and concomittant rise in NE levels. On the other hand, treatment of melatonin in both LP and SP bird groups resulted in an increase in the quantity of both E and NE compared to respective values in adrenals of melatonin injected NP birds. However, relative to the amount of E and NE in adrenals of placebo treated LP and SP birds, significant effect of melatonin treatment was observed only in SP birds. The results suggest that influences of exogenous melatonin on the levels of both blood glucose and adrenal catecholamines are largely modulated by short rather than long photoperiods.

The Evaluation of Melatonin Effect Against The Early Effect of Ionizing Radiation Induced Lung Injury

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raziyeh tahamtan

2014-06-01

Results: the results indicated that radiation increases the collapse and fibrosis and cause the abundance of macrophage compared to control group (p<0.05. Oral administration of melatonin before radiation therapy significantly increased the lymphocyte and macrophage frequency (p<0.001 and decreased the RBC (p<0.05 frequency compared to the radiation group. Conclusion: According to the results, melatonin can prevent early damages in irradiated lungs. Free radicals cause cytotoxicity and melatonin can directly decrease the radiation induced cell damages by converting the free radicals to non- toxic compounds and also through the activation of the major antioxidant enzymes.

Protective effects of melatonin and ghrelin on spermatogenesis: A narrative review of the literature

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Mohammadreza Gholami

2017-09-01

Full Text Available Spermatocytogenesis starts from lumens of seminiferous cords and after migration to the basal membrane ends to the lumens again. We attempt to review the protective effects of melatonin and ghrelin on Spermatocytogenesis and in particular on spermatogonial stem cells, as two rather newly-discovered hormones. Testicular freezing prior to chemotherapy and radiotherapy is one of the ways of preserving fertility in children with cancer. The freezing has two methods of slow-freezing (cryopreservation and rapid-freezing (vitrification. Administration of melatonin can maintain the quality of the germ cells underwent such processes, as well as ghrelin, can protect germ cells from the toxicities secondary to ischemic injuries, and pathologic apoptosis. This review indicates that in vitro or in vivo administration of melatonin or ghrelin, could be effective to preserve fertilization and also they can be used in assisted reproductive technologies to improve the quality of sperms. Future original studies should be propelled toward human studies, of course with observing the ethics

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...

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...

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...

Melatonin-Based Therapeutics for Neuroprotection in Stroke

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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.

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

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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.

Melatonin modulates drug-induced acute porphyria

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Sandra M. Lelli

Full Text Available This work investigated the modulation by melatonin (Mel of the effects of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide (AIA and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC on oxidative environment, glucose biosynthesis and heme pathway parameters. Administration of Mel before rat intoxication with AIA/DDC showed a clear beneficial effect in all cases. Mel induced decreases of 42% and 35% in the excretion of the hemeprecursors 5-aminolevulinic acid (ALA and porphobilinogen (PBG, respectively, and a 33% decrease in the induction of the heme regulatory enzyme 5-aminolevulinic acid-synthase (ALA-S. The activity of the glucose metabolism enzyme phosphoenolpyruvate carboxykinase (PEPCK, which had been diminished by the porphyrinogenic treatment, was restored by 45% when animals were pre-treated with Mel. Mel abolished the modest decrease in glucose 6-phospatase (G6Pase activity caused by AIA/DDC treatment. The oxidative status of lipids was attenuated by Mel treatment in homogenates by 47%, whereas no statistically significant AIA/DDC-induced increase in thiobarbituric acid reactive substances (TBARS was observed in microsomes after Mel pre-treatment. We hypothesize that Mel may be scavenging reactive species of oxygen (ROS that could be damaging lipids, PEPCK, G6Pase and ferrochelatase (FQ. Additionally, Mel administration resulted in the repression of the key enzyme ALA-S, and this could be due to an increase in glucose levels, which is known to inhibit ALA-S induction. The consequent decrease in levels of the heme precursors ALA and PBG had a beneficial effect on the drug-induced porphyria. The results obtained open the possibility of further research on the use of melatonin as a co-treatment option in acute porphyria. Keywords: Melatonin, Glucose synthesis, Heme pathway, Acute porphyria, Oxidative stress

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

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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.

Transcutaneous Noninvasive Device for the Responsive Delivery of Melatonin in Microgravity., Phase I

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National Aeronautics and Space Administration — Our goal is develop a smart, transcutaneous device for individualized circadian (sleep) therapy by responsive release of melatonin, in microgravity. Additionally,...

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

Melatonin in Alzheimer’s Disease

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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.

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.

Melatonin Inhibits the Proliferation of Gastric Cancer Cells Through Regulating the miR-16-5p-Smad3 Pathway.

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Zhu, Chenyu; Huang, Qun; Zhu, Hongyu

2018-03-01

The incidence and mortality of gastric cancer is steadily increasing annually around the world, which required further investigation about alternative therapy strategies. Melatonin, an indoleamine synthesized in the pineal gland, has shown dramatic anticancer effect in several cancers, however, the function of melatonin in gastric cancer needs to be characterized. In this study, we found that melatonin inhibited the growth and induced apoptosis of gastric cancer cells. microRNAs (miRNAs) have been attractive targets for many anticancer drugs. To explore the underlying molecular mechanism by which melatonin attenuated the growth of cancer cells, miRNA microarray analysis was performed to screen the miRNAs, which significantly altered after melatonin treatment. The result showed that melatonin administration enhanced the expression of miR-16-5p. Further molecular mechanism research revealed that miR-16-5p targeted Smad3 and consequently negatively regulated the abundance of Smad3. Consistently, melatonin exposure decreased the level of Smad3 and overexpression of Smad3 attenuated the inhibitory effect of melatonin in gastric cancer cells. These results uncovered the anticancer effect of melatonin and highlighted the critical roles of miR-16-5p-Smad3 pathway in melatonin-induced growth defects of gastric cancers.

Melatonin, mitochondria and hypertension.

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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.

Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy

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Andersen, Lars Peter Holst; Kücükakin, Bülent; Werner, Mads U

2014-01-01

mg of intravenous (IV) melatonin or placebo were administered at the time of surgical incision. MEASUREMENTS: Pain was assessed by a set of questionnaires documenting "pain at rest" using a visual analog scale (VAS). The use of rescue medication was recorded. Sleep quality and general well-being were...

The first experience of melatonin administration for correction of sleep disturbances in rheumatoid arthritis patients

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A. E. Karateev

2004-01-01

Full Text Available Objective. To assess efficacy melatonin administered for correction of sleep disturbances in pts with rheumatoid arthritis (RA. Material and methods. 3-weeks randomized controlled study of melatonin (Melaxen, Unipharm 3 mg/day (in the evening in 20 RA pts with sleep disturbances was performed. Control placebo group included 10 pts comparable with study group. Effect of the drug on insomnia so as on the main clinical and laboratory indices of RA activity was scored. Results. To the end of follow up study group pts showed improvement of sleep quality in comparison with initial. Frequency of such insomnia signs as feeling of dissatisfaction with night sleep, tiredness persistence after sleep and unpleasant feelings during sleep significantly decreased. The general result of treatment with melaxen was assessed by pt and doctor as improvement or significant improvement in 47,4-63,2% of cases. Morning stiffness, swollen and tender joint counts so as pain intensity significantly decreased during treatment. Improper drug tolerability was noted in only one pt. Signs of insomnia and RA activity did not change in placebo group. Conclusion. Melatonin is an effective and safe drug for correction of sleep disturbances in RA pts. It also showed capacity to decrease inflammatory activity of RA.

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

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

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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.

Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

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Manda, K.; Bhatia, A. L.

2004-07-01

Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs.

Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

International Nuclear Information System (INIS)

Manda, K.; Bhatia, A. L.

2004-01-01

Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs

Melatonin in antinociception: its therapeutic applications.

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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.

Melatonin Activates Endoplasmic Reticulum Stress and Apoptosis in Rats with Diethylnitrosamine-Induced Hepatocarcinogenesis.

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Andrea Janz Moreira

Full Text Available Hepatocellular carcinoma (HCC is one of the most lethal human cancers worldwide because of its high incidence, its metastatic potential and the low efficacy of conventional treatment. Inactivation of apoptosis is implicated in tumour progression and chemotherapy resistance, and has been linked to the presence of endoplasmic reticulum stress. Melatonin, the main product of the pineal gland, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects in HCC cells, but these effects still need to be confirmed in animal models. Male Wistar rats in treatment groups received diethylnitrosamine (DEN 50 mg/kg intraperitoneally twice/once a week for 18 weeks. Melatonin was given in drinking water at 1 mg/kg/d, beginning 5 or 12 weeks after the start of DEN administration. Melatonin improved survival rates and successfully attenuated liver injury, as shown by histopathology, decreased levels of serum transaminases and reduced expression of placental glutathione S-transferase. Furthermore, melatonin treatment resulted in a significant increase of caspase 3, 8 and 9 activities, polyadenosine diphosphate (ADP ribose polymerase (PARP cleavage, and Bcl-associated X protein (Bax/Bcl-2 ratio. Cytochrome c, p53 and Fas-L protein concentration were also significantly enhanced by melatonin. Melatonin induced an increased expression of activating transcription factor 6 (ATF6, C/EBP-homologous protein (CHOP and immunoglobulin heavy chain-binding protein (BiP, while cyclooxygenase (COX-2 expression decreased. Data obtained suggest that induction of apoptosis and ER stress contribute to the beneficial effects of melatonin in rats with DEN-induced HCC.

No effect of melatonin on oxidative stress after laparoscopic cholecystectomy

DEFF Research Database (Denmark)

Kücükakin, B.; Klein, M.; Lykkesfeldt, Jens

2010-01-01

melatonin and 21 patients received placebo during surgery. No significant differences were observed between the groups in the oxidative stress variables MDA, TAA, AA and DHA or in the inflammatory variable CRP (repeated-measures ANOVA, P > 0.05 for all variables). Conclusions Administration of 10 mg...

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

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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.

Melatonin and pregnancy in the human.

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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.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

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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.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

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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

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

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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.

Melatonin: an Inhibitor of Breast Cancer

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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

Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

International Nuclear Information System (INIS)

Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

1988-01-01

The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted)

Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.

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Itzhak, Y; Martin, J L; Black, M D; Ali, S F

1998-06-01

Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH

Melatonin prevents possible radiotherapy-induced thyroid injury.

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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.

Role of melatonin in embryo fetal development.

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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.

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

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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.

Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials

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Ashwin Kamath

2018-01-01

Full Text Available The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = −4.44 [95% CI, −7.00 to −1.88]; p=0.0007; I2 = 13%, but not the systolic blood pressure (mean difference = −4.23 [95% CI, −8.11 to −0.36]; p=0.03; I2 = 0%. Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials.

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Kamath, Ashwin; Rather, Zahoor Ahmad

2018-01-01

The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = -4.44 [95% CI, -7.00 to -1.88]; p = 0.0007; I 2 = 13%), but not the systolic blood pressure (mean difference = -4.23 [95% CI, -8.11 to -0.36]; p = 0.03; I 2 = 0%). Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats.

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Pai, Sarayu A; Majumdar, Anuradha S

2014-12-01

This study was undertaken to study the effects of melatonin on metabolic and reproductive aspects of polycystic ovary syndrome (PCOS) in rats. PCOS was induced by daily subcutaneous administration of testosterone (20 mg/kg) to 21-day-old female rats for 35 days. Rats were given metformin (500 mg/kg), melatonin (1 mg/kg) or melatonin (2 mg/kg) along with testosterone. One group served as vehicle control. On the 36th day, the animals were euthanised, and anthropometrical, biochemical (glucose, insulin, lipids, testosterone, C reactive protein (CRP)), oral glucose tolerance test, and histopathological evaluation of ovaries, uterus and intraabdominal fat (IAF), were carried out. Daily colpocytological examination was carried out from 14(th) day of study until termination. Both the doses of melatonin significantly reduced body weight, body mass index, IAF, insulin and CRP. A favourable lipid profile, normal glucose tolerance and a decrease in the percentage of estrus smears were observed. Histopathological examination of ovary, uterus and IAF revealed a decrease in the number of cystic follicles, decrease in neoplastic endometrial glands, and decrease in adipocyte hypertrophy, respectively. The effects observed with melatonin were comparable to that with metformin. The study provides evidence of the potential beneficial effects of melatonin in PCOS. © 2014 Royal Pharmaceutical Society.

Effect of Using Melatonin Implants on Reproductive Performances in Turcana Ewes

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Ioan Pădeanu

2011-10-01

Full Text Available It is estimated by some authors that the administration of subcutaneous melatonin implants during a period of 30 days, in lactating or dry ewes, would improve the reproductive performance in some sheep breeds. This study was conducted in Giarmata Mare, Timis County, on 78 lactating ewes and 75 dry ewes, which were individually inserted with implants containing 18 mg melatonin on 31 August 2009. Control group consisted of 100 lactating and dry ewes in equal proportions. The results shown that the main reproduction indices as prolificacy, birth rate and the lamb number productivity index are significantly (p < 0.05 higher in ewes from the experimental group, compared with ewes from the control group, and that treated ewes shortened the period of mating and lambing to half-time comparing to the control group. There is a suggestion that the use of melatonin implants Melovin ® type near the normal breeding season increases the reproductive performance of ewes from Turcana breed.

Melatonin receptors: Current status, facts, and hypothesis

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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

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

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Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

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

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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.

Melatonin as Protection Against Radiation Injury

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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...

Radioprotective Effect and Follow-up of Melatonin as Antifertility Drug in Male Adult Mice submitted to Whole-Body γ Irradiation

International Nuclear Information System (INIS)

Tawfik, S.S.; Mansour, H.H.; El-Shamy, E.; Sallam, M.H.

2006-01-01

Melatonin is universal antioxidant for both man and animals and a substance normally produced in the human body. Radioprotective and follow up of melatonin as anti-fertility drug in whole body γ-irradiated male adult mice were studied. The alterations occurred in reproductive system and biochemical aspects in mice were evaluated. Control group, melatonin treated (received 10 mg/kg body wt for 20 successive days), following up for melatonin treated (2 recovery periods; 60 and 120 days), irradiated (2 Gy-γ-rays), pre-treated (received melatonin before irradiation) and following up for pre-treated (2 recovery periods) groups were designed. Body and testes wt, micronucleus test (MN), chromosomal aberration (CA), seminal plasma melatonin, sperm quality (count, motility and abnormal forms) and hormonal assay in serum (melatonin, testosterone, FSH and prolactin) were recorded for fertility assessment. Oxidative parameters in testis tissue (malonaldehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and nitric oxide (NO)) and biochemical assay (protein and lipid fractions in serum) were investigated for judgment melatonin radioprotective efficacy. Irradiation intensifies the processes of lipo peroxidation and oxidative modification of lipids and proteins with synchronized inhibition of the anti oxidative protection system. Melatonin administration against a background of radiation caused a distinctly expressed antioxidant effect

The Effect of Antioxidant Melatonin on Mice Sensorimotor Gyri Following Induction of Brain Edema

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Narges Jan-Zadeh

2007-04-01

Full Text Available Objective: Many factors can have a neuroprotective role after brain damage. The neuroprotective Effect of melatonin as a highly potent antioxidant and a free radical scavenger is well known. The purpose of this study was to investigate the effect of such melatonin on mice sensorimotorcortex after cold injury. Materials & Methods: In order to test such this objective, melatonin was injected intraperitoneally in 1,5,50 and 100 mg/kg to the mice (prepared by cortical cold injury induced brain lesion at the parietal lobe within three intervals (0.5 h before injury, 12 h and 48 h after injury. Brains were removed 72 hours after injury. Appropriate brain sections were stained with cresyl fast violet for histological assessment of cerebral cortex structures by using light microscope (LM. Results: After cell count of alive cells in the cerebral cortex the results showed that the cold injury caused significantly reduction in living cells. Melatonin administration in the experimental groups increased such living cells in compare to model group. Alive cells in cerebral cortex of animals which received melatonin at lower doses (1 and 5 mg/kg were lower than the control group, melatonin at optimum dose (50 mg/kg did not show any significant change in the number of alive cells in comparing with the control group (P>0/05. The highest dose (100mg/kg was toxic. Conclusion: Melatonin with optimum dose can reduce cerebral cortex damage due to cold injury in mouse model and overcome cell damages fallowing injury.

Alcoholic fermentation induces melatonin synthesis in orange juice.

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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.

Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway.

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Chang, Mingtao; Li, Yang; Liu, Dong; Zhang, Lianyang; Zhang, Hongguang; Tang, Hao; Zhang, Huayu

2016-08-01

Exogenous administration of melatonin has been demonstrated to down-regulate inflammatory responses and attenuate organ damage in various models. However, the salutary effect of melatonin against secondary intra-abdominal hypertension (IAH) remains unclear. This study sought to test the influence of melatonin on secondary IAH in a pathophysiological rat model and the underlying mechanisms involved. Before resuscitation, male rats underwent a combination of induced portal hypertension, applying an abdominal restraint device, and hemorrhaging to mean arterial pressure (MAP) of 40mmHg for 2h. After blood reinfusion, the rats were treated with lactated Ringer solution (LR) (30mL/h), melatonin (50mg/kg) +LR, and SB-203580 (10μmol/kg)+LR. LR was continuously infused for 6h. MAP, the inferior vena cava pressure and urine output were monitored. Histopathological examination, immunofluorescence of tight junction proteins, and transmission electron microscopy were administered. Intestinal permeability, myeloperoxidase activity, malondialdehyde, glutathione peroxidase, and levels of TNF-a, IL-2, and IL-6, were assessed. The expression of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, translocation of nuclear factor kappa B subunit, signal transducers and activators of transcription and tight junction proteins were detected by Western blot. We found that melatonin inhibited the inflammatory responses, decreased expression of p38 MAPK, attenuated intestinal injury, and prevented secondary IAH. Moreover, administration of SB203580 abolished the increase in p38 MAPK and also attenuated intestinal injury. These data indicate that melatonin exerts a protective effect in intestine in secondary IAH primarily by attenuating the inflammatory responses which are in part attributable to p38 MAPK inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH

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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

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

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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…

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

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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.

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

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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.

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

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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.

The Beneficial Effects of Melatonin Administration Following Hypoxia-Ischemia in Preterm Fetal Sheep

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Tamara Yawno

2017-09-01

Full Text Available Melatonin (MLT is an endogenous hormone that controls circadian cycle. MLT has additional important properties that make it appealing as a neuroprotective agent—it is a potent anti-oxidant, with anti-apoptotic and anti-inflammatory properties. MLT is safe for administration during pregnancy or to the newborn after birth, and can reduce white matter brain injury under conditions of chronic fetal hypoxia. Accordingly, in the current study, we examined whether an intermediate dose of MLT could restore white matter brain development when administered after an acute hypoxic ischemic (HI insult in preterm fetal sheep. Fifteen fetal sheep at 95–98 days gestation were instrumented with femoral artery and vein catheters, and a silastic cuff placed around the umbilical cord. At 102 days gestation, the cuff was inflated, causing complete umbilical cord occlusion for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses were administered saline alone. Ten days after HI, the fetal brain was collected from each animal and white and gray matter neuropathology assessed. HI caused a significant increase in apoptotic cell death (TUNEL+, activated microglia (Iba-1+, and oxidative stress (8-OHdG+ within the subventricular and subcortical white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin density. MLT administration following HI decreased apoptosis, inflammation and oxidative stress within the white matter. MLT had intermediate benefits for the developing white matter: it increased oligodendrocyte cell number within the periventricular white matter only, and improved CNPase+ myelin density within the subcortical but not the striatal white matter. MLT administration following HI was also associated with improved neuronal survival within the cortex. Neuropathology in preterm infants is complex and mediated by multiple mechanisms

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...

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

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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.

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)

Daily Socs1 rhythms alter with aging differentially in peripheral clocks in male Wistar rats: therapeutic effects of melatonin.

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Vinod, Ch; Jagota, Anita

2017-06-01

Suprachiasmatic nucleus (SCN) in synchronization with the peripheral clocks regulates the temporal oscillations leading to overt rhythms. Aging leads to attenuation of such circadian regulation, accompanied by increased inflammatory mediators prevalently the cytokines. Suppressors of cytokine signaling (SOCS) family of proteins such as SOCS 1, 3 and cytokine-inducible SH2-containing protein (CIS) negatively regulate the cytokine signaling pathway. The role of SOCS1 in aging and circadian system is obscure. We therefore studied the daily rhythms of rSocs1 mRNA expression at Zeitgeber time (ZT) -0, 6, 12 and 18 in peripheral clocks such as liver, kidney, intestine and heart of 3, 12 and 24 months (m) old male Wistar rats. Interestingly the peripheral clocks studied displayed a rhythmic rSocs1 gene expression in 3 months. In 12 months group, 12 h phase advance in liver and 12 h phase delay in kidney and heart was observed with abolition of rhythms in intestine. Aging (24 months group) resulted in a phase advance by 6 h in liver and heart with abolition of rhythms in intestine in 24 months group. Kidney was also significantly affected upon aging with significant decrease in the rSocs1 levels and abolition of rhythms. The decrease in melatonin levels with aging is associated with decreased immunity and increased oxidative stress. The exogenous administration of melatonin has been linked to play a role in re-synchronization of circadian rhythms, reducing oxidative stress and enhancing immune properties. We therefore had studied the effect of exogenous melatonin upon age induced changes in daily rSocs1 gene expression patterns. Melatonin treatment partially restored the rhythms and daily pulse (ratio of maximum:minimum levels) in liver and intestine in 12 months group. Melatonin administration resulted in a significant increase in mean 24 h rSocs1 expression in intestine and heart of 24 months group compared to that of 3 months. The melatonin administration

Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

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Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

2014-09-01

Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

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.

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.

Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

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Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

2013-01-01

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

Melatonin, mitochondria, and the metabolic syndrome.

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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.

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

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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.

Potency of melatonin in living beings.

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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.

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

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

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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.

Current role of melatonin in pediatric neurology: clinical recommendations.

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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.

POTENTIAL USE OF MELATONIN IN PROCEDURAL ANXIETY AND PAIN IN CHILDREN UNDERGOING BLOOD WITHDRAWAL.

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Marseglia, L; Manti, S; D'Angelo, G; Arrigo, T; Cuppari, C; Salpietro, C; Gitto, E

2015-01-01

The recognition of the value of pain, especially in the pediatric population, has increased over the last decade. It is known that pain-related anxiety can increase perceived pain intensity. There are several different approaches to the treatment of pre-procedural anxiety and procedural pain in children. Melatonin, a neurohormone with the profile of a novel hypnotic-anaesthetic agent, plays an important role in anxiolysis and analgesia. This study investigated the effects of oral melatonin premedication to reduce anxiety and pain in children having blood samples taken. The investigations were carried out on 60 children, aged 1-14 years, divided into 2 equal groups. Using a computer-generated randomization schedule, patients were given either melatonin orally (0.5 mg/kg BW, max 5 mg) or placebo 30 min before blood draw. Pre-procedural anxiety was assessed using the scale from the Children’s Anxiety and Pain Scales, while procedural pain used the Face, Legs, Activity, Cry and Consolability assessment tool for children under the age of 3 years, Faces Pain Scale-Revised for children aged 3-8 years and Numeric Rating Scale for children over the age of 8 years. Oral administration of melatonin before the blood withdrawal procedure significantly reduced both anxiety (pchildren under 3 years and pchildren over 3 years). These data support the use of melatonin for taking blood samples due to its anxiolytic and analgesic properties. Further studies are needed to support the routine use of melatonin to alleviate anxiety and pain in pediatric patients having blood samples taken.

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

Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

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Sisodia, Rashmi; Kumari, Seema; Verma, Rajesh Kumar; Bhatia, A L [Neurobiology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004 (India)

2006-06-15

Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy.

Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome.

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Corrales, Andrea; Vidal, Rebeca; García, Susana; Vidal, Verónica; Martínez, Paula; García, Eva; Flórez, Jesús; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

2014-01-01

The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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.

Administration of melatonin in drinking water promotes the phase advance of light-dark cycle in senescence-accelerated mice, SAMR1 but not SAMP8.

Science.gov (United States)

Asai, M; Ikeda, M; Akiyama, M; Oshima, I; Shibata, S

2000-09-08

We analyzed effects of aging on behavioral rhythms in the mouse showing senescence acceleration, SAMP8 strains. The free-running rhythms had longer free-running periods (tau) in SAMP8 than in the control strain (SAMR1). Drinking of melatonin promoted the adaptation to advanced LD in SAMR1 but not in SAMP8, although both strains exhibited melatonin MT1 and MT2 receptors. The present results suggest that melatonin promotes the adaptation to advanced LD cycles in normal aging mice.

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...

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.

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...

Role of melatonin combined with exercise as a switch-like regulator for circadian behavior in advanced osteoarthritic knee.

Science.gov (United States)

Hong, Yunkyung; Kim, Hyunsoo; Lee, Seunghoon; Jin, Yunho; Choi, Jeonghyun; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-11-14

Here, we show the role of melatonin combined with or without exercise as a determinant of multicellular behavior in osteoarthritis. We address the relationship between the molecular components governing local circadian clock and changes in the osteoarthritic musculoskeletal axis. Melatonin was injected subcutaneously in animals with advanced knee osteoarthritis (OA) for 4 weeks. Concurrently, moderate treadmill exercise was applied for 30 min/day. Morphometric, histological, and gene/protein-level analyses were performed in the cartilage, synovium, bone, and gastrocnemius muscle. Primary cultured chondrocytes repeatedly exposed to TNF-α were used in an in vitro study. The symptoms of OA include gait disturbance, osteophyte formation, and abnormal metabolism of the extracellular matrix (ECM) of the cartilage. Low-level expression of clock genes was accompanied by aberrant changes in cartilage specimens. Nanomolar doses of melatonin restored the expression of clock-controlled genes and corrected the abnormal chondrocyte phenotype. Melatonin combined with or without exercise prevented periarticular muscle damage as well as cartilage degeneration. But prolonged melatonin administration promoted the proteolytic cleavage of RANKL protein in the synovium, leading to severe subchondral bone erosion. These musculoskeletal changes apparently occurred via the regulation of molecular clock components, suggesting a role of melatonin as a switch-like regulator for the OA phenotype.

Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

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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

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.

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,

The benefit of a supplement with the antioxidant melatonin on redox status and muscle damage in resistance-trained athletes.

Science.gov (United States)

Leonardo-Mendonça, Roberto C; Ocaña-Wilhelmi, Javier; de Haro, Tomás; de Teresa-Galván, Carlos; Guerra-Hernández, Eduardo; Rusanova, Iryna; Fernández-Ortiz, Marisol; Sayed, Ramy K A; Escames, Germaine; Acuña-Castroviejo, Darío

2017-07-01

Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg·day -1 of melatonin or placebo 30 min before bedtime during 4 weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG·GSH -1 and GPx·GRd -1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

Clinical significance of melatonin receptors in the human myometrium.

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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.

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A.

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Miyata, Rie; Tanuma, Naoyuki; Sakuma, Hiroshi; Hayashi, Masaharu

2016-01-01

Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2'-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

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Rie Miyata

2016-01-01

Full Text Available Xeroderma pigmentosum group A (XPA is a genetic disorder in DNA nucleotide excision repair (NER with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA. The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep.

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González-Candia, Alejandro; Veliz, Marcelino; Araya, Claudio; Quezada, Sebastian; Ebensperger, Germán; Serón-Ferré, María; Reyes, Roberto V; Llanos, Aníbal J; Herrera, Emilio A

2016-08-01

Intrauterine growth restriction is a condition in which the fetus has a birthweight and/or length Intrauterine growth restriction can be associated with various causes, among which is low uteroplacental perfusion and chronic hypoxia during gestation. Often, intrauterine growth-restricted fetuses have increased oxidative stress; therefore, agents that decrease oxidative stress and increase utero, placental, and umbilical perfusion have been proposed as a beneficial therapeutic strategy. In this scenario, melatonin acts as an umbilical vasodilator and a potent antioxidant that has not been evaluated in pregnancies under chronic hypoxia that induce fetal growth restriction. However, this neurohormone has been proposed as a pharmacologic therapy for complicated pregnancies. The aim of this study was to determine the effects of prenatal administration of melatonin during the last trimester of pregnancy on the biometry of the growth-restricted lambs because of developmental hypoxia. Further, we aimed to determine melatonin and cortisol levels and oxidative stress markers in plasma of pregnant ewes during the treatment. High-altitude pregnant sheep received either vehicle (n = 5; 5 mL 1.4% ethanol) or melatonin (n = 7; 10 mg/kg(-1)day(-1) in 5 mL 1.4% ethanol) daily during the last one-third of gestation. Maternal plasma levels of melatonin, cortisol, antioxidant capacity, and oxidative stress were determined along treatment. At birth, neonates were examined, weighed, and measured (biparietal diameter, abdominal diameter, and crown-rump length). Antenatal treatment with melatonin markedly decreased neonatal biometry and weight at birth. Additionally, melatonin treatment increased the length of gestation by 7.5% and shifted the time of delivery. Furthermore, the prenatal treatment doubled plasma levels of melatonin and cortisol and significantly improved the antioxidant capacity of the pregnant ewes. Our findings indicate that antenatal melatonin induces further

Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

International Nuclear Information System (INIS)

Eybl, Vladislav; Kotyzova, Dana; Koutensky, Jaroslav

2006-01-01

The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50 mg/kg b.w., p.o.), resveratrol (20 mg/kg b.w., p.o.) or melatonin (12 mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7 mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates. Cadmium concentration was measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p < 0.001), decreased GSH content (to 65%, p < 0.001) and inhibited catalase (to 68%, p < 0.001) and GPx activity (to 60%, p < 0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p < 0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden

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

Developmental Programming of Adult Disease: Reprogramming by Melatonin?

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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.

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.

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

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.

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

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

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.

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

The role of melatonin in the light of current knowledge

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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.

Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery

DEFF Research Database (Denmark)

Madsen, Michael Tvilling; Voigt Hansen, Melissa; Andersen, Lærke Toftegård

2016-01-01

STUDY OBJECTIVES: To investigate whether administration of an oral dose of 6 mg melatonin before bedtime perioperatively in breast cancer surgery could change sleep outcomes measured by actigraphy. METHODS: This paper reports secondary outcomes from a double-blind, placebo-controlled, randomized...... clinical trial where patients received 6 mg melatonin (n = 27) or placebo (n = 21) approximately 60 minutes before bedtime 3 nights preoperatively until at least one week postoperatively. Participants were monitored in the entire period with actigraphy, and were instructed to complete visual analogue scale...... significantly changed sleep efficiency and wake after sleep onset after surgery, but had no effects on other objective sleep outcomes or on subjective sleep quality (VAS and KSS)....

Clinical uses of melatonin: evaluation of human trials.

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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.

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

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.

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.

Melatonin ve Klinik Önemi

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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...

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.

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)

Study on the influence of Sempervivum tectorum and Melatonin on Glutathion protective effects in rats blood exposed to Aluminum sulphate

Directory of Open Access Journals (Sweden)

Corina Gravila

2014-05-01

Full Text Available The present study was carried out to investigate the influence of Sempervivum tectorum aqueous extract and melatonin on reduced glutathione (GSH protective effect in Wistar albino rat blood exposed to aluminium sulphate- Al2(SO43. The rats were divided in one control group (C and 7 experimental groups (E. The control group received tap water. The experimental rats were feed the following way: E1 group – aluminum sulphate, daily, for 3 months; : E2 group – Sempervivum tectorum, daily, for 3 months; : E3 group – melatonin, daily, for 3 months; : E4 group – aluminum sulphate with Sempervivum tectorum, daily, for 3 months; : E5 group – aluminum sulphate with melatonin, daily, for 3 months; E6 group – aluminum sulphate, daily, for 3 months, and thereafter with Sempervivum tectorum for 1 month; E7 group – aluminum sulphate, daily, for 3 month, and thereafter with melatonin for 1 month. This study showed that Aluminum toxicity induced lower GSH. The oxidative stress caused by aluminum, given individual, is more pronounced than in the case in which aluminum is administered simultaneously with Sempervivum tectorum or melatonin. Decreasing GSH value is very small if Sempervivum tectorum or melatonin is given for one month, three months after the administration of aluminum. Effect induced by melatonin is more favorable than that of Sempervivum tectorum.

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

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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

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

Effects of prenatal gamma irradiation on postnatal development of the nervous system and some forms of behavior in rats: Melatonin effect

International Nuclear Information System (INIS)

Smajda, B.; Pipova, N.; Kiskova, T.

2017-01-01

The aim of our work was to find out whether irradiation of pregnant female rats with a dose of 1 Gy gamma rays during the most sensitive phase of CNS organogenesis causes a change in the intensity and time dynamics of neurogenesis in the hippocampus and whether these changes will correlate with changes in some selected behavioral parameters. Another objective was to investigate the protective effect of chronic administration of melatonin, an endogenous substance with proven antioxidant and genoprotective effects on neurogenesis processes in two age-differentiated groups of animals. The results showed a significant effect of a low dose of gamma rays applied during the sensitive phase of CNS embryogenesis on the intensity and time dynamics of neurogenesis in young and adult mammals. Melatonin administration has had a positive effect on cell proliferation and survival of mature neurons. From behavioral parameters, the positive effect of melatonin has only been shown to improve the long-term spatial memory of rats in the Morris swimming pool. (authors)

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...

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...

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.

Melatonin mitigates neomycin-induced hair cell injury in zebrafish.

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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.

THE MODULATION EFFECT OF MELATONIN AGAINST GAMMA IRRADIATION IN BIOCHEMICAL AND HISTOPATHOLOGICAL STUDIES ON MALE RATS

International Nuclear Information System (INIS)

ABDOU, M.I.; OSMAN, H.F.

2008-01-01

The objective of this study is to illustrate the radiomodulatory role of melatonin in the regulation of some biochemical and histopathological damage in case of total body irradiated rats.Male albino rats weighing 120-150 g were divided into four groups, group (I) control animals, group (II) animals received melatonin daily by gavages (3 mg/kg body weight) for two weeks, group (III) animals irradiated with 4 Gy Gamma rays and group (IV) animals irradiated with 4 Gy Gamma rays followed by daily administration with melatonin (3 mg/kg body weight) for two weeks. Rats were sacrificed on the 1st and 2nd week post-irradiation. Blood samples were collected for biochemical investigations. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), were determined as biomarkers of liver functions, urea and creatinine contents were measured as markers of kidney functions, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities were selected to evaluate heart damage. Alteration in the level of serum glucose was also determined. Tissue specimens from liver, kidney, heart and spleen were collected for the pathological studies.The results indicated that, the levels of liver enzymes, kidney functions and glucose were increased after irradiation of rats and reduced by the treatment with melatonin. These reductions were more noticed during the second weeks except in case of glucose which increased during the second week compared to the first week. On the other hand, heart enzymes levels were reduced by the effect melatonin which may be important for cardiopathological patients.Histopathological results showed that irradiation of rats induced tissue injuries in liver, kidney, heart and spleen.Melatonin treatment reduced these injuries to minimum.It could be concluded that, melatonin could be used as antioxidant to protect vital organs and their functions against irradiation since it works as free radicals

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.)

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.)

[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.

Effect of Day and Night Desflurane Anaesthesia on Melatonin Levels in Rats.

Science.gov (United States)

Özer, Figen Datlı; Öçmen, Elvan; Akan, Pınar; Erdost, Hale Aksu; Korkut, Sezen; Gökmen, Ali Necati

2016-08-01

The aim of this study is to investigate the effect of day and night administration of desflurane anaesthesia on melatonin levels in rats. Twenty-four 15-day-old rats were included in the study and were divided into four groups. The rats were anaesthetised between 19:00-01:00 (night group) and 07:00-13:00 (day group) with 5.7% desflurane concentration in 6 L min -1 100% oxygen. 6 L min -1 oxygen was administered to the control groups. At the end of 6 h of anaesthesia, blood samples were taken, and rats were sacrificed. Blood samples were centrifuged and melatonin levels from plasma samples were measured with radioimmunoassay. There was a statistically significant difference between the groups (p=0.007). Between group day control and group night control there was a statistically significant difference (p=0.042). Further, there was a significant difference between group day control and night desfluran as well (p=0.024). We could not find any difference between other groups. This study showed that 6 hours of 5.7% desflurane anaesthesia during day and night hours did not significantly change melatonin levels.

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

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.

Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

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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.

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

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.

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.

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.

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.

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.

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 ...

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.

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.

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

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.

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)

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

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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.

Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.

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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.

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

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

Melatonin Secretion during a Short Nap Fosters Subsequent Feedback Learning

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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.

High levels of melatonin generated during the brewing process.

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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.

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.

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

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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

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.

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

DEFF Research Database (Denmark)

Kucukakin, B.; Klein, M.; Lykkesfeldt, Jens

2010-01-01

melatonin and 21 patients received placebo during surgery. No significant differences were observed between the groups in the oxidative stress variables MDA, TAA, AA and DHA or in the inflammatory variable CRP (repeated-measures ANOVA, P > 0.05 for all variables). Conclusions Administration of 10 mg...

Gut Melatonin in Vertebrates: Chronobiology and Physiology

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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.

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

Melatonin Effects in Methylphenidate Treated Children with Attention Deficit Hyperactivity Disorder: A Randomized Double Blind Clinical Trial

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Mohammad Reza Mohammadi

2012-06-01

Full Text Available Objective: The aim of this study was to determine melatonin effects on sleep patterns, symptoms of hyperactivity and attention deficiency in children with attention-deficit hyperactivity disorder (ADHD.Methods: Children with age range of 7-12 years who had a combined form of ADHD were randomly divided in to 2 groups according to gender blocks. One group took melatonin (3 or 6mg combined with methylphenidate (Ritalin (1mg/kg, and the other group took placebo combined with methylphenidate (1mg/kg. ADHD rating scale and sleep patterns questionnaires were completed. Research hypotheses were assessed at the baseline, the second, fourth and eighth weeks after the treatment.Results: The mean sleep latency and total sleep disturbance scores were reduced in melatonin group, while the scores increased in the placebo group (p≥0.05. Data analysis, using ANOVA with repeated measures, did not show any statistically significant differences between the two groups in ADHD scores.Conclusion: Administration of melatonin along with methylphenidate can partially improve symptoms of sleep disturbance. However, it does not seem to reduce attention deficiency and hyperactivity behavior of children with ADHD.

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

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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.

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.

Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model

DEFF Research Database (Denmark)

Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q

2015-01-01

. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced...... by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal...... thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined...

Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy.

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Sharma, Rachana D; Katkar, Gajanan D; Sundaram, Mahalingam S; Swethakumar, Basavarajaiah; Girish, Kesturu S; Kemparaju, Kempaiah

2017-05-01

Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Melatonin as potential inducer of Th17 cell differentiation.

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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.

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

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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.

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

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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.

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

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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.

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

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.

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

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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.

Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay

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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.

Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

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Porfirio MC

2017-08-01

Full Text Available Maria-Cristina Porfirio,1 Juliana Paula Gomes de Almeida,2 Maddalena Stornelli,1 Silvia Giovinazzo,1 Diane Purper-Ouakil,3 Gabriele Masi4 1Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, Italy; 2Unit of Child Neurology, Irmandade Santa Casa de Misericordia Hospital São Paulo, Brazil; 3Unit of Child and Adolescent Psychiatry, Saint Eloi Hospital, Montpellier, France; 4IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy Abstract: In the last two decades, second-generation antipsychotics (SGAs were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs can cause

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

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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.

Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells.

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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.

Effect of testosterone replacement on the alteration of steroid metabolism in the hypothalamic-preoptic area of male hamsters treated with melatonin.

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Petterborg, L J; West, D A; Rudeen, P K; Ganjam, V K

1991-11-01

Adult male hamsters were maintained under 14 hours of light per day and randomly assigned to groups that received daily afternoon melatonin (25 micrograms) or vehicle injections. Animals from both groups were killed following 4, 8, and 12 weeks of treatment. By 12 weeks, the melatonin-treated hamsters had significant reductions in the weights of the testes and seminal vesicles, serum testosterone levels, and activities did not differ between groups. In a second experiment, hamsters were hypothalamic-preoptic area (HPOA) aromatase activities. Hypothalamic-preoptic area 5 alpha-reductase activities did not differ between groups. In a second experiment, hamsters were again treated with melatonin or vehicle for 12 weeks prior to being killed. After 10 weeks of treatment, groups of melatonin-treated animals received subcutaneous silastic capsules (5, 10, or 20 mm) filled with testosterone. Animals in two other groups were given blank implants or no implants at all. Two weeks later, at autopsy, reproductive organ weights, serum testosterone levels, and HPOA aromatase activities were significantly suppressed by melatonin administration. 5 alpha-Reductase activity in the HPOA was not affected. Hamsters that had been given the 10- and 20-mm testosterone implants exhibited normal seminal vesicle weights and HPOA aromatase activities. These results suggest that melatonin-induced reduction of HPOA aromatase activity is mediated by decreased circulating levels of testosterone.

Melatonin prevents experimental preterm labor and increases offspring survival.

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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.

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

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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.

Effect of melatonin on kidney cold ischemic preservation injury

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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

Melatonin for Reducing Weight Gain Following Administration of Atypical Antipsychotic Olanzapine for Adolescents with Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

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Mostafavi, Seyed-Ali; Solhi, Mahmoud; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

2017-06-01

We aimed to evaluate melatonin effectiveness in weight gain reduction following olanzapine use for 11-17-year-old bipolar disorder patients. Seventy-seven adolescent outpatients, subsequent to their initial diagnosis of bipolar I disorder by a psychiatrist, entered this study. After assessing inclusion and exclusion criteria, 48 patients consented to participate. Twenty-four patients were allocated to receive olanzapine, lithium carbonate, and melatonin, and 24 patients were allocated to receive olanzapine, lithium carbonate, and placebo by simple randomization. The Young Mania Rating Scale (YMRS) was performed at baseline. Before treatment and after 6 and 12 weeks of treatment, weight, height, and body mass index (BMI) were measured. Analysis of variance (ANOVA) with repeated measure and t-test were used to analyze data. Nineteen patients in each group finished the study and their data were entered for analysis. Mean rise in BMI in the melatonin group compared with placebo (2.45 vs. 3.25 respectively) was marginally significant (t = 1.936; df = 36; p = 0.061). ANOVA with repeated measure also showed a marginally significant difference (F = 3.74; df = 1; p = 0.061) between groups and across time in regard to BMI. Mean body weight rise in the melatonin group compared with the placebo group (5.8 kg vs. 8.2 kg respectively) was marginally significant (t = 1.923; df = 28; p = 0.065). ANOVA with repeated measure also showed a marginally significant difference (F = 3.73; df = 1.1; p = 0.056) between groups and across time for body weight. Coadministration of melatonin with olanzapine and lithium carbonate in adolescents with bipolar disorder could reduce the sharp weight gain side effect of these drugs to near significance.

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)

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.

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder.

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Bonacci, Janene M; Venci, Jineane V; Gandhi, Mona A

2015-10-01

In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings. © The Author(s) 2014.

Melatonin and its correlation with testosterone in polycystic ovarian syndrome

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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

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.

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)

Melatonin Regulates Oxidative Stress Initiated by Freund’s Complete Adjuvant

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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.

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

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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.

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

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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.

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

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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

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.

The effect of the melatonin on cryopreserved mouse testicular cells

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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.

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)

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

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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.

Melatonin in sleepless children : everything has a rhythm?

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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

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

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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.

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

Effect of Melatonin Implants during the Non-Breeding Season on the Onset of Ovarian Activity and the Plasma Prolactin in Dromedary Camel

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Khalid El Allali

2018-03-01

results demonstrate that photoperiod appears to be involved in dromedary reproductive seasonality. Melatonin implants may be a useful tool to manipulate seasonality and to improve reproductive performance in this species. Administration of subcutaneous melatonin implants during the transition period to the breeding season following an artificial signal of long photoperiod have the potential to advance the breeding season in camels by about 2.5 months.

Effect of Melatonin Implants during the Non-Breeding Season on the Onset of Ovarian Activity and the Plasma Prolactin in Dromedary Camel

Science.gov (United States)

El Allali, Khalid; Sghiri, Abdelmalek; Bouâouda, Hanan; Achaâban, Mohamed Rachid; Ouzir, Mounir; Bothorel, Béatrice; El Mzibri, Mohammed; El Abbadi, Najia; Moutaouakkil, Adnane; Tibary, Ahmed; Pévet, Paul

2018-01-01

demonstrate that photoperiod appears to be involved in dromedary reproductive seasonality. Melatonin implants may be a useful tool to manipulate seasonality and to improve reproductive performance in this species. Administration of subcutaneous melatonin implants during the transition period to the breeding season following an artificial signal of long photoperiod have the potential to advance the breeding season in camels by about 2.5 months. PMID:29594158

Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

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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.

Melatonin and the electron transport chain.

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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.

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

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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.

Vibrational and electronic spectroscopic studies of melatonin

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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.

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

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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.

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

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Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

2017-09-15

Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

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....

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

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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.

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

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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.

Melatonin redirects carbohydrates metabolism during sugar starvation in plant cells.

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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.

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

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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.

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.

MECHANISMS OF MELATONIN EFFECTS UPON IMMUNE STATE IN EXPERIMENTAL DESYNCHRONOSES PRODUCED UNDER THE LED ILLUMINATION CONDITIONS

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M. V. Osikov

2015-01-01

. Suppression of Th1- and Th2-dependent immune response is found to develop in accordance with reduction in IFNγ and IL-4. Melatonin administration in desynchronosis (a total of 30 mg/kg resulted in recovery of blood leukocyte counts, ROS generation by phagocytes, higher intensity of Th1- and Th2-dependent immune response, cortisol, IFNγ and IL-4 concentrations in blood serum, like as stimulation of blood phagocytic capacity. Restoration of Th1- and Th2-dependent immune response is associated with normalized concentrations of, respectively, IFNγ and IL-4 levels in blood serum.

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

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

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

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

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

2014-01-01

Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her

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

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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.

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.

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.

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

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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.

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

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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…

Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: as a Model

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Sergio D. Paredes

2009-01-01

Full Text Available In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age-related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove ( Streptopelia risoria as a suitable model.

Melatonin and Ischemic Stroke: Mechanistic Roles and Action

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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.

Melatonin and Ischemic Stroke: Mechanistic Roles and Action.

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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.

Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

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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

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

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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

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

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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.

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

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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.

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

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

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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....

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

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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

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

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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.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

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Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...

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

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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

Dose dependent sun protective effect of topical melatonin

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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....

Color indirect effects on melatonin regulation

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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.

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.

The influence of melatonin on metabolic changes in female rats induced by continuous irradiation and/or administration of 7,12-dimethylbenz/a/anthracene

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Ahlers, I.; Solar, P.; Ahlersova, E.; Kassayova, M.; Smajda, B.

1997-01-01

Metabolic profile is an important biological marker of neoplastic processes not only in the tumor itself but also in the host organism. The neuro-hormone melatonin has been implicated in the experiments as an oncostatic agent. Female Wistar:Han SPF rats (Velaz, Prague, Czech Republic) were irradiated continuously for 15 days using a daily gamma rays dose of 96 mGy. At the end of exposure one group of rats was administered 5 mg/kg b.w. of dimethylbenz/a/anthracene (DMBA) intragastrically. During the period of exposure to ionizing radiation a part of the animals was supplied with melatonin (M) at a concentration of 20 μl/ml in drinking water. Selected parameters of lipid and carbohydrate metabolism and levels of selected hormones were determined 2, 30 and 100 days post-irradiation. The irradiation itself caused only small changes in tissue lipids. The application of a single low dose (subthreshold from the point of view of induction of mammary tumors) of DMBA caused more pronounced changes in nonirradiated animals; of the changes observed an increase in lipids in the liver, triacylglycerol (TG) in the thymus and decrease in myocardial glycogen predominated. The intake (by drinking) of exogenous M prevented the biochemical pattern of fatty liver in animals administered DMBA in both groups, irradiated an nonirradiated. A Prolonged effect of exogenous M, demonstrated by prevention of increase in TG in the thymus and of irradiated animals caused by administration of DMBA, was observed. The mechanism of metabolic effect of M is not known. Additional experiments are needed to explain the relationship between the beneficial effect of M on metabolic changes and its presumable oncostatic effect in rats. (author)

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

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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.

Melatonin: current status and future perspectives in plant science

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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.

Melatonin: Bone Metabolism in Oral Cavity

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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.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

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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.

Melatonin receptors: latest insights from mouse models

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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

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

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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.

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

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

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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.

Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

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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

Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells.

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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.

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.

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 ...

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

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Pere Barceló

2016-01-01

Full Text Available Growth hormone (GH and melatonin are two hormones with quite different physiological effects. Curiously, their secretion shows parallel and severe age-related reductions. This has promoted many reports for studying the therapeutic supplementation of both hormones in an attempt to avoid or delay the physical, physiological, and psychological decay observed in aged humans and in experimental animals. Interestingly, the effects of the external administration of low doses of GH and of melatonin were surprisingly similar, as both hormones caused significant improvements in the functional capabilities of aged subjects. The present report aims at discerning the eventual difference between cognitive and motor effects of the two hormones when administered to young and aged Wistar rats. The effects were tested in the radial maze, a test highly sensitive to the age-related impairments in working memory and also in the rotarod test, for evaluating the motor coordination. The results showed that both hormones caused clear improvements in both tasks. However, while GH improved the cognitive capacity and, most importantly, the physical stamina, the effects of melatonin should be attributed to its antioxidant, anxiolytic, and neuroprotective properties.

Relationship between plasma and salivary melatonin and cortisol investigated by LC-MS/MS.

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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.

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)

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

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 ...

Exogenous melatonin improves Malus resistance to Marssonina apple blotch.

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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.

Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model

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Sergio D. Paredes

2009-01-01

Full Text Available In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age- related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove (Streptopelia risoria as a suitable model.

Effect of melatonin supplementation on pregnancy outcome in Wistar-Kyoto and Sprague-Dawley rats.

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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.

Melatonin potentiates glycine currents through a PLC/PKC signalling pathway in rat retinal ganglion cells.

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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

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

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.

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.

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

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)

Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

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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.

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...

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

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...

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.

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

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.

Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

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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...

Melatonin Is Involved in Regulation of Bermudagrass Growth and Development and Response to Low K+ Stress

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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

Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in Apple Leaf

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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.

Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

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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.

[Potential of melatonin for prevention of age-related macular degeneration: experimental study].

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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.

Current knowledge on the melatonin system in teleost fish.

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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.

Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus.

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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.

Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus

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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.

The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

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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.

Effect of topical application of melatonin cream 12.5% on cognitive parameters

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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...

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

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C.D. Cisternas

2010-09-01

Full Text Available We studied the effects of adverse conditions such as constant light (LL on the circadian rhythm of malate (MDH, EC 1.1.1.37 and lactate (LDH, EC 1.1.1.27 dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28, anxiety-like behavior (elevated plus-maze test at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark, LL (light from day 10 to 21 of pregnancy, and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy. LL offspring did not show circadian rhythms of MDH (N = 62 and LDH (N = 63 activities (cosinor and ANOVA-LSD Fisher. They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test, an increase in mounting (94.4%, intromission (94.5% and ejaculation (56.6% latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12 compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher, anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

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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.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

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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.

Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

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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.

Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

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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.

Influences of graded dose of melatonin on the levels of blood glucose and adrenal catecholamines in male roseringed parakeets (Psittacula krameri ) under different photoperiods.

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Maitra, S K; Dey, M; Dutta, S; Bhattacharya, S; Dey, R; Sengupta, A

2000-12-01

Effects of daily evening (just before the onset of darkness in a 24 h light dark cycle) administration of graded doses (25, 50, or 100 microg/100 g body wt./day for 30 days) of melatonin on the concentrations of blood glucose and adrenal catecholamines were studied in sexually active male roseringed parakeets under natural (NP; approximately 12L: 12D) and artificial long (LP; 16L: 8D) and short (SP; 8L: 16D) photoperiods. Blood samples and adrenal glands were collected from each bird during the mid-day on the following day of the last treatment. The concentrations of glucose in blood and epinephrine (E) and norepinephrine (NE) in the adrenals were measured. The results of the study indicated that exogenous melatonin induces hypo- or hyperglycemia depending on the dose of hormone administered as well as to the length of photoperiod to which birds were exposed. The levels of E and NE in the adrenals were shown also to vary in relation to photoperiod and the dose of melatonin administered. But the nature of the influence of melatonin becomes different under altered photoperiodic conditions. It appears that short photoperiods are more effective than long photoperiods as a modulator of glycemic and adrenal catecholaminergic responses to exogenous melatonin. A statistically significant correlation between the levels of blood glucose and that of E and NE in the adrenals was found in the control birds, but not in the melatonin treated birds. The results suggested that the responses of blood glucose and adrenal catecholamines to the treatment with melatonin in the roseringed parakeets may not be dependent on each other.

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

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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.

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

High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

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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.

Night work, light exposure and melatonin on work days and days off.

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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.

Progressive decrease of melatonin production over consecutive days of simulated night work.

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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

Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx.

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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.

Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells

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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

Negative regulation of neuromedin U mRNA expression in the rat pars tuberalis by melatonin.

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Sayaka Aizawa

Full Text Available The pars tuberalis (PT is part of the anterior pituitary gland surrounding the median eminence as a thin cell layer. The characteristics of PT differ from those of the pars distalis (PD, such as cell composition and gene expression, suggesting that the PT has a unique physiological function compared to the PD. Because the PT highly expresses melatonin receptor type 1, it is considered a mediator of seasonal and/or circadian signals of melatonin. Expression of neuromedin U (NMU that is known to regulate energy balance has been previously reported in the rat PT; however, the regulatory mechanism of NMU mRNA expression and secretion in the PT are still obscure. In this study, we examined both the diurnal change of NMU mRNA expression in the rat PT and the effects of melatonin on NMU in vivo. In situ hybridization and quantitative PCR analysis of laser microdissected PT samples revealed that NMU mRNA expression in the PT has diurnal variation that is high during the light phase and low during the dark phase. Furthermore, melatonin administration significantly suppressed NMU mRNA expression in the PT in vivo. On the other hand, 48 h fasting did not have an effect on PT-NMU mRNA expression, and the diurnal change of NMU mRNA expression was maintained. We also found the highest expression of neuromedin U receptor type 2 (NMUR2 mRNA in the third ventricle ependymal cell layer, followed by the arcuate nucleus and the spinal cord. These results suggest that NMU mRNA expression in the PT is downregulated by melatonin during the dark phase and shows diurnal change. Considering that NMU mRNA in the PT showed the highest expression level in the brain, PT-NMU may act on NMUR2 in the brain, especially in the third ventricle ependymal cell layer, with a circadian rhythm.

Ghrelin and melatonin as biomarkers in patients with giardiasis

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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.

Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

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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

Antioxidative effects of melatonin on kinetics, microscopic and oxidative parameters of cryopreserved bull spermatozoa.

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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.

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

Effects of melatonin and prolactin in reproduction: review of literature.

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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.

Effects of melatonin and prolactin in reproduction: review of literature

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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.

Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

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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.

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

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

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.

Melatonin treatment of pediatric residents for adaptation to night shift work.

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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.

Endogenous melatonin and oxidatively damaged guanine in DNA

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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

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.

Melatonin Nanoparticles Adsorbed to Polyethylene Glycol Microspheres as Activators of Human Colostrum Macrophages

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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.

Dietary melatonin alters uterine artery hemodynamics in pregnant holstein heifers

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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...

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 ...

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

New insights on the spectrophotometric determination of melatonin pKa values and melatonin-βCD inclusion complex formation constant

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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.

Concentration-dependent effect of melatonin on DSPC membrane

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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.

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

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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

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

DEFF Research Database (Denmark)

Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...... benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life....

Adaptations of the aging animal to exercise: role of daily supplementation with melatonin.

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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.

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)

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,

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.

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.

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

Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

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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.

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.

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

Analysis of miRNA expression profiles in melatonin-exposed GC-1 spg cell line.

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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.

Evaluating The Effect of Melatonin on HAS2, and PGR expression, as well as Cumulus Expansion, and Fertility Potential in Mice.

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Ezzati, Maryam; Roshangar, Leila; Soleimani Rad, Jafar; Karimian, Nahid

2018-04-01

Infertility is a worldwide health problem which affects approximately 15% of sexually active couples. One of the factors influencing the fertility is melatonin. Also, protection of oocytes and embryos from oxidative stress inducing chemicals in the culture medium is important. The aim of the present study was to investigate if melatonin could regulate hyaluronan synthase-2 (HAS2) and Progesterone receptor (PGR) expressions in the cumulus cells of mice oocytes and provide an in vitro fertilization (IVF) approach. In this experimental study, for this purpose, 30 adult female mice and 15 adult male mice were used. The female mice were superovulated using 10 U of pregnant mare serum gonadotropin (PMSG) and 24 hours later, 10 U of human chorionic gonadotropin (hCG) were injected. Next, cumulus oocyte complexes (COCs) were collected from the oviducts of the female mice by using a matrix-flushing method. The cumulus cells were cultured with melatonin 10 μM for 6 hours and for real-time reverse transcription-polymerase chain reaction (RT-PCR) was used for evaluation of HAS2 and PGR expression levels. The fertilization rate was evaluated through IVF. All the data were analyzed using a t test. The results of this study showed that HAS2 and PGR expressions in the cumulus cells of the mice receiving melatonin increased in comparison to the control groups. Also, IVF results revealed an enhancement in fertilization rate in the experimental groups compared to the control groups. To improve the oocyte quality and provide new approaches for infertility treatment, administration of melatonin as an antioxidant, showed promising results. Thus, it is concluded that fertility outcomes can be improved by melatonin it enhances PGR. Copyright© by Royan Institute. All rights reserved.

Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer.

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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.