Increasing Concentrations Of Melatonin Research Articles

A Combination of Rosa Multiflora and Zizyphus Jujuba Enhance Sleep Quality in Anesthesia-Induced Mice.

Sleep is an essential component of quality of life. The majority of people experience sleep problems that impact their quality of life. Melatonin is currently a representative sleep aid. However, it is classified as a prescription drug in most countries, and consumers cannot purchase it to improve their sleep. This sleep induction experiment in mice aimed to identify a natural combination product (NCP) that can create synergistic sleep-promoting effects. Based on the mechanism of action of sleep, we investigated whether phenomenological indicators of sleep quality change according to the intake of NCP. The sleep onset and sleep time of the mice that consumed the NCP found by this study were improved compared to the existing sleep aids. The mean melatonin level in the blood increased by 197% compared to the control. To our knowledge, this is the first study to demonstrate that Rosa multiflora Thunb. (Yeongsil) can promote sleep similarly to Zizyphus jujuba Miller (Sanjoin). The results indicate a preclinical study of NCPs containing Rosa multiflora Thunb and Zizyphus jujuba Miller developed by us showed significant differences in sleep incubation and duration depending on melatonin concentrations. Our results also suggest that increased melatonin concentrations in the blood are likely to improve sleep quality, especially regarding incubation periods.

Pleiotropic actions of melatonin in testicular peritubular myoid cells of immature Syrian hamsters

BackgroundPeritubular myoid cells are emerging as key regulators of testicular function in adulthood. However, little is known about the role of testicular peritubular myoid cells (TPMCs) in the development of the male gonad. We found that, compared to testes of young adult hamsters, gonads of 21 day-old animals show increased melatonin concentration, seminiferous tubular wall thickening and a heterogeneous packaging of its collagen fibers thus raising the question whether melatonin may be involved in the regulation of TPMCs. MethodsWe established primary cultures of TPMCs from immature hamsters (ihaTPMCs), which we found express melatonergic receptors. ResultsExogeneous melatonin decreased the levels of inflammatory markers (NLRP3 inflammasome, IL1β) but increased the expression of cyclooxygenase 2 (COX2, key enzyme mediating prostaglandin synthesis) and of the glial cell line-derived neurotrophic factor (GDNF) in ihaTPMCs. Melatonin also stimulated ihaTPMCs proliferation and the expression of extracellular matrix proteins such as collagen type I and IV. Furthermore, collagen gel contraction assays revealed an enhanced ability of ihaTPMCs to contract in the presence of melatonin. ConclusionMelatonin regulates immune and inflammatory functions as well as contractile phenotype of the peritubular wall in the hamster testis. General significanceIf transferable to the in vivo situation, melatonin-dependent induction of ihaTPMCs to produce factors known to exert paracrine effects in other somatic cell populations of the gonad suggests that the influence of melatonin may go beyond the peritubular wall and indicates its contribution to testicular development and the establishment of a normal and sustainable spermatogenesis.

Serum melatonin in dogs with congenital portosystemic shunting, with and without hepatic encephalopathy

BackgroundMelatonin is a hormone produced and secreted primarily by the pineal gland and mainly metabolised in the liver. Increased melatonin concentrations have been reported in human cirrhosis and hepatic encephalopathy...

Daytime melatonin and light independently affect human alertness and body temperature

Light significantly improves alertness during the night (Cajochen, Sleep Med Rev, 11, 2007 and 453; Ruger et al., AJP Regul Integr Comp Physiol, 290, 2005 and R1413), but results are less conclusive at daytime (Lok et al., J Biol Rhythms, 33, 2018 and 589). Melatonin and core body temperature levels at those times of day may contribute to differences in alerting effects of light. In this experiment, the combined effect of daytime exogenous melatonin administration and light intensity on alertness, body temperature, and skin temperature was studied. The goal was to assess whether (a) alerting effects of light are melatonin dependent, (b) soporific effects of melatonin are mediated via the thermoregulatory system, and (c) light can improve alertness after melatonin‐induced sleepiness during daytime. 10 subjects (5 females, 5 males) received melatonin (5 mg) in dim (10 lux) and, on a separate occasion, in bright polychromatic white light (2000 lux). In addition, they received placebo both under dim and bright light conditions. Subjects participated in all four conditions in a balanced order, yielding a balanced within‐subject design, lasting from noon to 04:00 pm. Alertness and performance were assessed half hourly, while body temperature and skin temperature were measured continuously. Saliva samples to detect melatonin concentrations were collected half hourly. Melatonin administration increased melatonin concentrations in all subjects. Subjective sleepiness and distal skin temperature increased after melatonin ingestion. Bright light exposure after melatonin administration did not change subjective alertness scores, but body temperature and proximal skin temperature increased, while distal skin temperature decreased. Light exposure did not significantly affect these parameters in the placebo condition. These results indicate that (a) exogenous melatonin administration during daytime increases subjective sleepiness, confirming a role for melatonin in sleepiness regulation, (b) bright light exposure after melatonin ingestion significantly affected thermoregulatory parameters without altering subjective sleepiness, therefore temperature changes seem nonessential for melatonin‐induced sleepiness, (c) subjective sleepiness was increased by melatonin ingestion, but bright light administration was not able to improve melatonin‐induced sleepiness feelings nor performance. Other (physiological) factors may therefore contribute to differences in alerting effects of light during daytime and nighttime.

Effect of night light regimen on growth performance, antioxidant status and health of broiler chickens from 1 to 21 days of age.

ObjectiveThe study was conducted to evaluate the effects of night light regimen on growth performance, antioxidant status and health of Lingnan Yellow broiler chickens from 1 to 21 days of age.MethodsA completely randomized factorial design involved 2 photoperiods (constant lighting [CL], 24 L:0 D and intermittent lighting [INL], 17 L:3 D:1 L:3 D)×2 light intensities (10 lx and 30 lx). A total of one thousand six hundred and eighty 1-d-old Lingnan Yellow broiler chicks were randomly divided into 4 treatments with 6 replicates (70 birds per replicate). The experiment lasted for 21 d.ResultsPhotoperiods and light intensities had no effect on average daily gain, feed conversion ratio, and mortality of the broiler chickens (p>0.05). The INL had a significant effect on average daily feed intake (p<0.05) of broiler chickens compared with CL. Photoperiod and light intensity had an interactive effect on melatonin (MT) concentration (p<0.05). At CL, reducing light intensity increased MT concentration; INL birds had higher MT but MT concentration was not affected by light intensity. There was an interactive effect on glutathione peroxidase (GPx) and catalase (CAT) in serum and total antioxidant capability (T-AOC) in liver between photoperiod and light intensity. With the decrease of light intensity, the activities of GPx and CAT in serum and T-AOC in liver increased in CL group (p<0.05). Broiler chickens reared under INL had better antioxidant status and 10 lx treatments had higher activities of CAT in serum than 30 lx (p<0.05). Different photoperiods and light intensities had no effect on malondialdehyde. There was an interaction between photoperiod and light intensity on serum creatine kinase (CK) concentration (p<0.05). At CL, the elevated light intensity resulted in an increase in CK content; INL birds had lower CK concentration especially in low light intensity group. Besides, INL and low light intensity significantly reduced the concentration of serum corticosterone and heat shock protein 70 (p<0.05). Serum immunoglobulin M contents were increased in broiler chickens reared under the INL compared with CL group (p<0.05).ConclusionResults above suggest that the night light regimen of INL and 10 lx could be beneficial to the broiler chickens from 1 to 21 days of age due to the better health status and electricity savings.

Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

It has been suggested that disturbances in melatonin (MEL) secretion might play a role in osteoporosis development in females with anorexia nervosa (AN). It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue. We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system. Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA), immunoradiometric assay (IRMA) or enzyme-linked immunosorbent assay (ELISA) methods. Our study participants with AN showed a significant reduction in body mass and body mass index (BMI), a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00) as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a significant and independent predictor of OPG, cortisol and FT3 were significant and independent predictors of sRANKL, while LH, E2, Δ MEL2.00/9.00 and FT3 were significant predictors of the OPG/sRANKL ratio. Alterations in OPG and sRANKL levels observed in girls with AN are associated with changes in nocturnal MEL secretion, the circadian rhythm of MEL, and LH, E2, FT3 and cortisol levels. Dysregulation of the relationships between MEL and LH, E2, FT3 and cortisol found in girls with AN might affect the balance of the OPG/sRANKL system. Low values of the OPG/sRANKL ratio associated with high OPG and sRANKL levels suggest some defect in the mechanism compensating for bone remodeling disturbances.

Seasonal effects of central leptin infusion on secretion of melatonin and prolactin and on SOCS-3 gene expression in ewes

Recent studies have demonstrated photoperiodic changes in leptin sensitivity of seasonal mammals. Herein, we examined the interaction of season (long days (LD) versus short days (SD)) and recombinant ovine leptin (roleptin) on secretion of melatonin and prolactin (PRL) and on mRNA expression of suppressor of cytokine signaling-3 (SOCS-3) in the medial basal hypothalamus (MBH) in sheep. Twenty-four Polish Longwool ewes, surgically fitted with third ventricle (IIIV) cannulas, were utilized in a replicated switchback design involving 12 ewes per season. Within-season and replicate ewes were assigned randomly to one of three treatments (four ewes/treatment) and infused centrally three times at 0, 1 and 2 h beginning at sunset. Treatments were 1) control, Ringer-Locke buffer; 2) L1, roleptin, 0.5 microg/kg BW; and 3) L2, roleptin, 1.0 microg/kg BW. Jugular blood samples were collected at 15-min intervals beginning immediately before the start of infusions and continued for 6 h. At the end of blood sampling, a washout period of at least 3 days elapsed before ewes were re-randomized and treated with one of the treatments described above (four ewes/treatment). Ewes were then killed and brains were collected for MBH processing. Leptin treatments increased (P<0.001) circulating leptin concentrations compared with controls during both seasons in a dose-dependent manner. Overall, mean plasma concentrations of melatonin were greater (P<0.001) during LD than SD. However, leptin treatments increased melatonin concentrations during SD in a dose-dependent manner and decreased it during LD. Similarly, plasma concentrations of PRL were greater (P<0.001) during LD than SD. However, unlike changes in melatonin, circulating PRL decreased (P<0.001) in response to leptin during LD. Semi-quantitative PCR revealed that leptin increased (P<0.001) SOCS-3 expression in the MBH region during LD in a dose-dependent manner. Data provide evidence that secretion of photoperiodic hormones such as melatonin and PRL are inversely regulated by leptin during SD and LD. However, the increase in expression of SOCS-3 in the MBH during LD compared with SD fails to fully explain these effects.

Increased melatonin concentrations in children with growth hormone deficiency

A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1-16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below -2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children.

Spontaneous central melatonin secretion and resorption kinetics of exogenous melatonin: a ventricular CSF study.

Pineal secretion of melatonin, a potential sleep-inducing agent, is stimulated by nighttime darkness. To gain better insight into the control of melatonin physiology in man, we studied melatonin concentrations in ventricular cerebrospinal fluid (v-CSF). In four patients aged 1-4 yr with therapeutic v-CSF drainage, including one with lumbar CSF (l-CSF) drainage, CSF samples were collected sequentially over 24-hr periods. One further patient with severe sleep disturbance had one collection period under chloral hydrate and another after oral melatonin administration. Reduction of light intensity or night periods, respectively, led to increased melatonin levels. At the moment of falling asleep, additional melatonin peaks were observed in v-CSF but not in l-CSF. Oral melatonin, but not chloral hydrate, caused a rapid increase in CSF melatonin between 10 and 80 min after intake, raising levels far beyond physiological concentrations. The commencement of sleep is associated with an additional melatonin peak v-CSF which is independent of baseline secretion during the day-night cycle. The possibility is discussed that the induction of sleep might depend on a critical level or increased melatonin concentrations, which can be achieved with orally administered melatonin.

Melatonin stimulates glutathione peroxidase activity in human chorion.

In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87 +/- 10.87 nM/L; chorionic homogenate, 4.36 +/- 1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P < 0.001), with peak levels occurring at 3 hr (51.68 +/- 3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia.

Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brain.

Melatonin is a powerful scavenger of oxygen free radicals. In humans, melatonin is rapidly transferred from the maternal to the fetal circulation. To investigate whether or not maternal melatonin administration can protect the fetal rat brain from radical-induced damage by increasing the activities of antioxidant enzymes, we administered melatonin to pregnant rats on day 20 of gestation. Melatonin (10 mg/kg) was injected intraperitoneally at daytime (14:00 hr) and, to remove the fetuses, a laparotomy was performed at 1, 2, or 3 hr after its administration. We measured the melatonin concentration in the maternal serum and in fetal brain homogenates and determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in fetal brain homogenates. Melatonin administration markedly increased melatonin concentrations in the maternal serum and fetal brain homogenates, with peak levels achieved 1 hr after melatonin administration (serum: 538.2+/-160.7 pM/mL; brain homogenates: 13.8+/-2.8 pM/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in fetal brain homogenates increased significantly (P<0.01). Similarly, SOD activity increased significantly between 1 and 2 hr after melatonin administration (P<0.01). These results indicate that melatonin administration to the mother increases antioxidant enzyme activities in the fetal brain and may thereby provide indirect protection against free radical injury. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve excessive free radical production, such as fetal hypoxia and preeclampsia.

The development of circadian rhythms in a human infant.

This study examines the ontogeny and interaction of circadian rhythms of sleep, wake, temperature, melatonin, and feeding in the human newborn, and the influence of photic and non-photic factors on the initiation of entrainment. An infant's sleep-wake state, temperature, and salivary melatonin were monitored from birth to 6 months. Temperature was obtained every hour, and the infant's sleep/eating onset/termination were observed continuously and recorded until day 182. Salivary melatonin was obtained weekly for a 24-hour period, starting at week 3. The infant slept in his parents' bedroom. All household members awakened, retired, and ate meals according to a fixed schedule during the study, while the infant ate, slept, and woke on demand. A healthy male infant was the subject. Biological parents gathered data continuously for six months. The infant's schedule was on-demand; the household's was fixed. Illumination was restricted to sunlight. The circadian rhythm of temperature appeared first, soon after birth, and became statistically significant within one week. The wake circadian rhythm appeared second, attaining significance at day 45; approximately the same time that increased melatonin concentration began to occur at sunset. The sleep circadian rhythm appeared last, attaining significance after day 56. Ninety to 120 minute zones of sustained wakefulness first appeared in the second month of life subsequent to awakening and prior to sleep onset. The infant's nocturnal sleep-onset was coupled to sunset before day 60 and subsequently to family bedtime, giving evidence of initial photic entrainment followed by social entrainment. Circadian rhythms appeared much more rapidly in this infant than previously reported; their rapid appearance was probably facilitated by maximal exposure to sunlight, and regular social cues. These lighting conditions replicate universal infant experience prior to the invention of artificial light.

Skin lipids in rats administered with melatonin

Effects of the pineal hormone melatonin on skin lipids in Wistar rats were studied by thinlayer chromatography. The reaction was shown to be delayed. Contents of total lipids and the majority of fractions increased over 24 h after administration of melatonin. Concentrations of triglycerides and phospholipids decreased, while the contents of cholesterol, cholesterol esters, and free fatty acids increased by the end of the second day. Our findings indicate that the blood and subcutaneous fat, as well as changed metabolic interrelations of skin lipids are involved in the skin response to increased melatonin concentration.

Effect of light therapy on salivary melatonin in seasonal affective disorder

To investigate the role of a light-induced advance in the timing of the melatonin rhythm in seasonal affective disorder, 11 depressed patients underwent 2 weeks of light therapy with full spectrum or cool white light. Evening saliva samples were collected before and after each week of treatment and assayed for melatonin to determine the time of onset of nocturnal secretion. Both treatments reduced depression scores, advanced the timing of the melatonin rhythm, and increased melatonin concentrations. Time of onset of the nocturnal increase in melatonin did not differ between clinical responders and nonresponders, suggesting that a phase advance in the onset of nocturnal melatonin secretion is not sufficient to induce clinical remission in seasonal affective disorder.

Melatonin rhythms in Arctic urban residents.

The 24-hr rhythm of salivary melatonin was measured in persons living in the city of Tromsø (70 degrees N) at the following times of the year: in January at a day length of 2 hr of twilight, in June under continuous sunshine, and in March and September at about 12 hr light and 12 hr darkness. The hormone patterns varied widely between individuals, but, in general, they were consistent within most individuals between the seasons. Highest peak values occurred in January when the mean level was also significantly higher than at any other time of year. The lowest mean levels occurred in June. Although individual rhythms were not always apparent, the mean patterns showed significantly elevated melatonin concentrations during the night at all seasons. The June melatonin peak was similar to that in March and September, but appeared to be phase-delayed with increased melatonin concentrations from midnight until 0900. It is assumed that the delayed melatonin peak in June may be associated with a tendency among people to shift their activity/rest rhythm and that the pineal sensitivity to light is reduced in the morning in summer.