• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.497-503
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• 2001

Evidence from the last 10 years have been suggested that melatonin mainly produce a depressant effect on the cardiac system, but we found an activating effect of melatonin on heart rate in this research. To determine the hypothesis that melatonin has dual effects on physiological behaviour of cardiac system, we investigated the effects of melatonin on heart rate in isolated rat atria and anesthetized rats. Regardless of concentration, melatonin produced bradycardia in the 84 cases of 148 experiments (57 %) and tachycardia in the 64 cases of 148 experiments (43 %). And in atrium, melatonin produced a decrease automaticity in 52 cases of 86 experiments (60 %) and increase automaticity in 40 % (34/86 cases). Also, these effects are not significnat relationship with concetration of melatonin. The melatonin-induced bradycardia in vivo was inhibited by pretreatment of atropine or bilateral cervical vagotomy. Also, in isolated atrium the melatonin-induced decrease in automaticity was inhibited by pretreatment of atropine. These melatonin-induced responses were potenitated by pretreatment of propranolol. The melatonin-induced tachycardia in vivo was inhibited by pretreatment of propranolol, nifedipine or bilateral cervical vagotomy, but not by pretreatment of atropine. The melatonin-induced incease in automaticity in isolated atrium was converted to decrease in automaticity by pretreatment of propranolol. In addition, the change in heart rate caused by adrenoceptor agonists was inhibited by pretreatment of melatonin. These results indicate that melatonin-induced bradycardia may be related to a muscarinic receptor activation and melatonin-induced tachycardia may be related to a $\beta$-adrenoceptor stimulation.

• Journal of Radiation Protection and Research
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• v.29 no.4
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• pp.237-242
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• 2004

The radioprotective effects of Melatonin and Ge-132 on acute hematopoietic injury was investigated in mice exposed to an acute whole-body radiation dose of 8 Gy. Melatonin was administered intraperitoneally 1 hour before irradiation at a dose of 200 mg/kg, and Ge-132 was administered orally from days 5 to 20 after irradiation at a dose 130 - 150 mg/kg/d. The radioprotective effects were evaluated for spleen using TUNEL assay, and in peripheral blood by counting lymphocyte & WBC. The 4 experimental groups (irradiation-only, melatonin pretreatment, Ge-132 posttreatment, and melatonin pretreatment plus Ge-132 posttreatment) were observed for survival analysis up to 30 days following irradiation. The apoptotic index (47.8% vs 45.9%, p=0.385), and the number of lymphocytes ($97/{\mu}{\ell}\;vs\;101/{\mu}{\ell}$, p=0.898) were not significantly different between the irradiation-only and the melatonin pretreatment group, But the number of WBCs ($147/{\mu}{\ell}\;vs\;306/{\mu}{\ell}$, p=0.010) was higher in the melatonin pretreatment group. The irradiation-only, melatonin, Ge-132, and melatonin plus Ge-132 treatments resulted in survival rate at 30 days of 21.4%, 100%, 35.7%, and 85.7%, respectively. The melatonin pretreatment group in survival analysis between groups was showed significantly higher survival than the irradiation-only(p=0.000), or Ge-132 posttreatment group(p=0.0003). These results indicate that the melatonin may have a potential as an effective radioprotector on acute hematopoietic syndrome following radiation exposure.

• Korean Journal of Food Science and Technology
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• v.34 no.6
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• pp.1145-1148
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• 2002

Melatonin, which is a hormone secreted from pineal gland of brain and known to prevent oxidative damages of various tissues, was analyzed in 26 domestic edible plants. For the preparation of melatonin fraction, 50% ethanol extract prepared from lyophilized plant powder was filtered and applied on TLC plate. Melatonin position on TLC developed with acetone was identified by fluorescence light and extracted with methanol. This methanolic fraction was injected into HPLC comprising ODS-A column, fluorescence detector, and mobile phase consisting of a mixture (30 : 70, v/v) of 70% ammonium acetate and methanol at a flow rate of 1.0 mL/min. Melatonin was identified at the retention time of 17 min. Results revealed that celery, leek, broccoli, and cauliflower had higher melatonin contents than others.

• Toxicological Research
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• v.16 no.2
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• pp.147-150
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• 2000

Melatonin plasma in Swallows exhibited circadian rhythmical secretions in the LD (Light and dark, 12：12) period with and without feeding. But their average difference between at CT6 (Circadian Time) and CT18 was 3.53 ng/$\textrm{m}{\ell}$ in LD period with feeding. on the other side 1.60 ng/$m\ell$ during without feeding. Melatonin concentration at CT6 without feeding incresed from 0.22 ng/$\textrm{m}{\ell}$ to 0.93 ng/$\textrm{m}{\ell}$. It is demonstrated that decresing melatonin secretion may reduce digestive function in order to ready for the migration. While the birds with feeding exhibited circadian rhythmical activity, their activity without feeding was durable. The concentrations of melatonin plasma by refeeding were 1.53 ng/$\textrm{m}{\ell}$ at CT6 and 6.07 ng/$\textrm{m}{\ell}$ at CT18. Melatonin plasma concentration in the night increased by more than ca. quadruple at day. This results suggest that melatonin regulates metabolism for the return to the normal metabolism condition after migration. After 3 days refeeding melatonin was secreted circadian rhythmically same as the secretions with feeding at beginning.

• Development and Reproduction
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• v.17 no.2
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• pp.111-119
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• 2013

Golden hamsters reproduce in a limited time of a year. Their sexual activities are active in summer but inactive in winter during which day length does not exceed night time and environmental conditions are severe to them. The reproductive activities are determined by the length of light in a day (photoperiod). Melatonin is synthesized and secreted only at night time from the pineal gland. Duration of elevated melatonin is longer in winter than summer, resulting in gonadal regression. The present study aimed at the influences of continuous melatonin treatments impinging on the gonadal function in male golden hamsters. Animals received empty or melatonin-filled capsules for 10 weeks. They were divided into long photoperiod (LP) and short photoperiod (SP). All the animals maintained in LP (either empty or melatonin-filled capsules) showed large testes, implying that melatonin had no effects on testicular functions. Animals housed in SP displayed completely regressed testes. But animals kept in SP and implanted with melatonin capsules exhibited blockage of full regression by SP. These results suggest that constant release of melatonin prohibits the regressing influence of SP.

• Korean Journal of Psychosomatic Medicine
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• v.5 no.2
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• pp.195-204
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• 1997

Objectives : The behavioral and physiological effects following low doses and high doses of melatonin have not been fully explored. In this study the authors investigated the nature and extent of the hypnotic effects, oral temperature, blood pressure effects, performance effects and subjective feelings following the acute administration of low pharmacological oral doses of melatonin at mid-day. Methods : Thirty-five healthy young medical students were randomly assigned to receive 6mg of oral melatonin(N=11), 12mg of oral melatonin(N=12) or a placebo(N=12) in a double-blind, placebo controlled trial. Measures of the behavioral and physiological effects used in the study were Stanford Sleepiness Scale, Digit Symbol Substitution Test, Trail test and visual analogue scale for subjective feelings. Oral temperature and blood pressure were measured. The subjects were studied between 10:00 and 16:00 hours. Data were analyzed by using repeated-measures analyses of variance(ANOVA). Results: Melatonin produced statistically significant effects on oral temperature, but there were no significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on oral temperature between the 12mg oral melatonin group and the placebo group at 12:00 and 16:00 hours, but no significant difference between the 12mg and the 6mg oral melatonin groups. Melatonin produced a dose-related increase in subjective sleepiness and had significant effects on time, the $dose{\times}time$ interaction. There was a significant difference on subjective sleepiness among the placebo, 6mg, 12mg oral melatonin groups at 13:00-16:00 hours. Melatonin did not produce statistically significant dose-related effects on subjective fatigue but produced significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on subjective fatigue between the 12mg, the 6mg oral melatonin groups and the placebo group at 13:00 hour. Conclusions : These data indicated that acute administration of melatonin at mid-day increased subjective sleepiness and fatigue but decreased oral temperatures. These effects were shown especially in 12mg oral melatonin group.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.160-160
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• 2003

Plasma melatonin in the seasonal light-period is circadian rhythmically secreted. Maximal secretion showed at 14 o'clock in summer- and winter-like period, but minimal secretion showed at 5 o'clock in summer-like period and at 8 in winter-like period. These times of minimal secretions were at the beginning of light period. Plasma melatonin in the light period is secreted 62.5% more than in the dark period in summer-like period and 45.9% more in winter-like period. Total plasma melatonin in winter-like period is secreted 56.5% more than in summer-like period. The weights of testis(-20.8%) and body(-7.1%) were reduced in the winter-like period. By the increase of plasma melatonin in mice, body- and testis-weights are decreased, on the contrary by the decrease of plasma melatonin in mice, body and testis weights are increased. In view of the results so far achieved melatonin changes on the body weight and reproductive organ in mice. It is presumed that melatonin effects on the metabolism and sex hormone.

• Environmental Analysis Health and Toxicology
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• v.18 no.1
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• pp.57-61
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• 2003

Plasma melatonin in the seasonal light-period is circadian rhythmically secreted. Maximal secretion showed at 14 o'clock in summer- and winter-like period, but minimal secretion showed at 5 o'clock in summer-like period and at 8 in winter-like period. These times of minimal secretions were at the beginning of light period. Plasma melatonin in the light period is secreted 62.5％ more than in the dark period in summer- like period and 45.9％ more in winter- like period. Total plasma melatonin in winter-like period is secreted 56.5％ more than in summer-like period. The weights of testis (-20.8％) and body (-7.1％) were reduced in the winter-like period. By the increase of plasma melatonin in mice, body - and testis -weights are decreased, on the contrary by the decrease of plasma melatonin in mice, body and testis weights are increased. In view of the results so far achieved melatonin changes on the body weight and reproductive organ in mice. It is presumed that melatonin effects on the metabolism and sex hormone.

• Journal of Photoscience
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• v.9 no.2
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• pp.29-32
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• 2002

Studies till date suggest the existence of a fetal biological clock in suprachiasmatic nuclei entrained by the circadian signal from mother. Melatonin from maternal pineal gland reaches to the fetus by crossing every biological barrier including placenta, hence fetuses were exposed to similar melatonin variation as their mother. Experimental modulations of maternal pineal gland activity of pregnant females either by exposing the them to different photoperiodic schedules or by exogenous melatonin treatments till the date of parturition, regulated the fetal plasma level of melatonin, thereby the prenatal (fetal) growth and development. This clearly suggests the maternal transport of melatonin to their fetus through placenta since fetal retina-hypothalamic tract was incomplete. An extension of experimental schedules till 60 days of post-partum period regulated the neonatal pineal gland activity and gonadal maturation along with their plasma levels of melatonin and sex steroids suggesting clearly the phenomenon of maternal transfer of melatonin to their young ones during the post-natal period, when the neonates were solely dependent on the mother's milk for their nutrition and energetic demands. On the basis of above observations we may suggest that the maternal pineal gland activity regulate the prenatal development by passing its melatonin to fetus via placenta and post-natal growth and sexual maturation by passing maternal melatonin to neonates via milk. Hence, the photoperiod perceived by mother is translated into the maternal plasma level of melatonin which not only regulates the prenatal but also the post-natal growth and sexual maturation of neonates.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.240-249
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• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.