• Journal of Embryo Transfer
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• v.24 no.4
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• pp.237-247
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• 2009

Melatonin (N-acetyl-5-methoxytryptamine) is the major neurohormone secreted during the night by the vertebrate pineal gland. The circadian pattern of pineal melatonin secretion is related to the biological clock within the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals. The SCN coordinates the body's rhythms to the environmental light-dark cycle in response to light perceived by the retina, which acts mainly on retinal ganglion cells that contain the photopigment melanopsin. Calbindin-D9k (CaBP-9k) is a member of the S100 family of intracellular calcium- binding proteins, and in this review, we discuss the involvement of melatonin and CaBP-9k with respect to calcium homeostasis and apoptotic cell death. In future studies, we hope to provide important information on the roles played by CaBP-9k in cell signal transduction, cell proliferation, and $Ca^{2+}$ homeostasis in vivo and in vitro.

• Journal of Photoscience
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• v.9 no.2
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• pp.472-474
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• 2002

Till date the phenomenon of maternal transfer of photic information was reported to regulate the fetal/neonatal growth, however its influence on neonatal immune system is still an enigma. In the present study, we observed an increase in maternal plasma melatonin level under short day length (SOL) condition with a consequent decrease in TLC and LC in their respective neonates. However, a significant decrease in maternal plasma melatonin level was noted under constant darkness (DD) with an increase in TLC and LC of their neonates. The blastogenic response (BGR) to Con A of splenocytes exhibited a significant increase in neonates of SDL females and a significant decrease in the neonates of DD females. Hence, it appears that the increase in maternal plasma melatonin under SOL condition transmitted information to decrease the immune status. Continuous exposure of females to darkness (DD) negatively regulated the maternal pineal gland activity thereby decreasing their plasma melatonin level. This information was transmitted for elevation of immune status in neonates, so that they exhibit better growth and sexual maturation. Therefore, we may suggest that the maternal photic information transmitted either prenatally through placenta or postnatally via the milk regulate the hormonal profile of Melatonin to regulate the immune status of neonates in order to influence their growth and sexual maturation.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.107-112
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• 2002

To investigate the feasibility of developing a novel melatonin plaster, the effects of vehicles and drug loading dose on the in vitro permeation of melatonin across dorsal hairless mouse skin from pressure-sensitive adhesive (PSA) matrices were examined. Vehicles employed were propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC) and diethylene glycol monoethyl ether (DGME). Among PSAs used, only $Duro-Tak^{\circledR}$ 87-2196 showed a good peeling property. The release from $Duro-Tak^{circledR}$ 87-2196 was proportional to the square root of time, and dose-dependent. The fluxes increased as the loading dose increased over the doses under solubility. The relatively high permeation flux $(3.03{\pm}1.37\;{\mu}g/cm^2/hr)$ was obtained when using PGMC at the melatonin loading dose of $45\;mg/140\;cm^2$. Lag time was not affected by the vehicles used but by the thickness spread. The melatonin plasters prepared using PGMC showed a good adhesive property onto skin, and showed no crystal formation.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.2
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• pp.87-92
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• 2022

Objective: The aim of this study was to determine the effects of melatonin and selenium in freezing extenders on frozen-thawed rat sperm. Methods: Semen samples were collected from 20 adult male Wistar albino rats. Following dilution, the samples were divided into six groups: four cryopreserved groups with 1 mM and 0.5 mM melatonin and selenium supplements, and two fresh and cryopreserved control groups. The rapid freezing technique was used to freeze the samples. Flow cytometry was used to assess plasma membrane integrity, mitochondrial membrane potential, and DNA damage, while computer-assisted sperm analysis was used to assess motility. Results: Total motility was higher in the 1 mM melatonin supplementation group than in the cryopreserved control group (mean±standard error of the mean, 69.89±3.05 vs. 59.21±1.31; p≤0.05). The group with 1 mM selenium had the highest plasma membrane integrity (42.35%±1.01%). The cryopreserved group with 0.5 mM selenium had the highest mitochondrial membrane potential, whereas the cryopreserved control group had the lowest (45.92%±4.53% and 39.45%±3.52%, respectively). Conclusion: Cryopreservation of rat semen supplemented with 1 mM melatonin increased sperm motility after freeze-thawing, while supplementation with 0.5 mM selenium increased mitochondrial activity.

• Korean Journal of Environmental Biology
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• v.20 no.3
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• pp.224-231
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• 2002

Photoperiod (length of light per day) is a major factor in regulating reproductive function in golden hamsters. The information of photoperiod is transmitted to the reproductive endocrine system by melatonin. Thus the effects of melatonin aye investigated in male golden hamsters exposed to photoperiods. Paired testicular weights were markedly reduced in the animals housed in short photoperiod $(SP,\le{12\;hours\;day^{-1})$ and injected with melatonin in the evening, but not in long photoperiod $(LP,\le{12.5}\;hours\;day^{-1})$ and injected with melatonin in the morning. The histological examination of regressed testes showed reduction of tubular lumen diameter including the numbers of cells and Leydig cell number. The mean values of both follicle stimulating hormone (FSH) and luteinizing hormone (LH) were also lowered in the sexually inactive animals than in the sexually active animals. Melatonin receptor was identified by reverse-transcription polymerase chain reaction (RT-PCR) and its expression was examined in various tissues to scrutinize the action site of melatonin. It turned out 309 nucleotides and was definitely expressed in hypothalamus and pituitary including spleen, retina, and epididymis. And gonadotropin releasing hormone (GnRH) gene, which is a key element in regulating reproduction, was identified by RT-PCR but the expression of GnRH was not modified by the treatment of melatonin. Taken together, photoperiod via melatonin indirectly affects reproductive endocrine system, possibly through the release of GnRH, not the synthesis of GnRH.

• Archives of Plastic Surgery
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• v.35 no.6
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• pp.645-652
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• 2008

Purpose: In skin flap surgery, surgeons often encounter distal ischemia of the flap. If a powerful free radical scavenger is used, it may reduce the formation of free radical and improves the survival of flap. Thus, the present study purposed to examine whether the survival of flap can be enhanced by administering melatonin, which is known to be a powerful free radical scavenger a antioxidant molecule. Methods: We divided 40 Sprague-Dawley rats into 4 groups, 10 in each group. For the control group(n=10), we intraperitoneally injected only carrier solution once 30 minutes before the operation, and once a day for 7 days from the day of operation. Among the experimental groups, a group(n=10) was administered with dimethyl sulfoxide(DMSO), in another group(n=10), melatonin was intraperitoneally injected, and in the other(n=10) melatonin was intraperitoneally injected and applied topically(2 cc of 1% melatonin) to the operation site. Caudally based skin flaps measuring $3{\times}10cm^2$ were elevated on the mid-dorsum of the rats. and then repositioned. On the seventh postoperative day, the survival area of the flap was measured and tissues were examined under the light microscope. Results: The control group, the DMSO group, the melatonin administration group and the melatonin administration and application group showed the mean survival rates of $55.26{\pm}9.2%$, $70.29{\pm}7.47%$, $81.45{\pm}4.14%$ and $86.1{\pm}1.52%$, respectively, for $30cm^2$ of flap. Compared to the control group, the experimental groups showed a significantly high increase in survival area at significance level of 95%. Conclusion: In this study, the survival rate of flap was enhanced through the administration of melatonin after flap surgery. This suggests that melatonin not only functions as a powerful free radical scavenger and oxygen radical scavenger but also stabilizes and protects cells, and by doing so, enhances the survival of moderately injured ischemic sites in the distal end of flap.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.223-230
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• 2001

Melatonin, a pineal gland hormone, is believed to act as an antioxidant via the stimulation of radical detoxifying enzymes and scavenging of free radicals. In this study, effects of in vitro and in vivo treatments of melatonin on the cisplatin-induced lipid peroxidation, LDH release and plasma creatinine were determined in rabbit renal cortical cells. The level of malondialdehyde (MDA) was assayed as an index of lipid peroxidation and the level of LDH release as an indicator of cellular damage. In in vitro studies, cisplatin increased the levels of MDA and LDH release in a concentration-and time-dependent manner. Melatonin inhibited the cisplatin-induced lipid peroxidation and LDH release in a concentration-dependent manner. The minimal effective concentration of melatonin that significantly reduced the $300\;{\mu}M$ cisplatin-induced lipid peroxidation and LDH release was 1 mM. In in vivo studies, the levels of lipid peroxidation and LDH release in renal cortical cells increased significantly 24 or 48 hours after a single injection of cisplatin (6 mg/kg). When the cisplatin-injected rabbits were pretreated with 10 mg/kg of melatonin, a significant reduction in both lipid peroxidation and LDH release was observed. The plasma creatinine level increased from $0.87{\pm}0.07$ mg/dl in control to $6.33{\pm}0.54$ mg/dl in cisplatin-injected rabbits (P＜0.05). Melatonin partially prevented the increase in serum creatinine level $(1.98{\pm}0.11\;mg/dl)$ by cisplatin (P＜0.05). In the proximal tubules from cisplatin-treated group, tubular cells had microvilli of variable heights. Necrotic debris was seen in tubular lumens. In most of cells, the mitochondria and lysosomes were increased in frequency. The endocytic vacuoles were not prominent and distribution of the brush border was irregular and shortened. These cisplatin-induced morphological changes were moderate in the melatonin-pretreated group. These results suggest that the toxicity of cisplatin is associated with the generation of reactive oxygen free radicals and that melatonin is a powerful antioxidant, which prevents some of the adverse effects of cisplatin.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.4
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• pp.266-274
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• 2020

Objectives: Melatonin induces human stem cells, converts pre-osteoblasts to mature osteoblasts, and reduces the duration of this transition. However, melatonin itself prevents activation of osteoclasts. Here, we evaluate the role of melatonin in prevention of bisphosphonate-related osteonecrosis of the jaw. Materials and Methods: In this experimental-interventional study, 30 rats were evaluated in 3 groups. The first and second groups received saline and zoledronic acid, respectively, for 4 weeks and the third group received 4 weeks of zoledronic acid and 3 weeks of melatonin simultaneously. First-right-maxillary-molar extraction was performed for all animals, which were sacrificed after 4 weeks of recovery. The extraction sockets were examined histologically for the presence of osteonecrosis, number of osteoclasts and fibroblasts, severity of inflammation, and vascularization. Data were analyzed by chi-square, one-way ANOVA, Tukey, Kruskal-Wallis and Fisher's exact statistical tests (α=0.05). Results: Osteonecrosis was observed in 20%, 90%, and 70% of the first, second and third groups, respectively (P=0.008). The lowest number of osteoclasts and fibroblasts was seen in the third group. Conclusion: Melatonin may effectively prevent some undesirable side effects of bisphosphonates. However, further studies are required to confirm the results of this study.

• BMB Reports
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• v.33 no.6
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• pp.463-468
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• 2000

Anthrax lethal toxin, which consists of two separate protein, protective antigen (83 KDa) and lethal factor (85 KDa) is responsible for major symptoms and death from systemic infection of Bacillus anthracis. High concentrations of this toxin are cytolytic to macrophages, whereas sublytic concentrations of lethal toxin induce these cells to produce interleukin $1{\beta}$ ($IL-1{\beta}$). It is proposed that melatonin and dehydroepiandrosterone (DHEA) may play an important role in modifying immune dysfunction. In this study, we investigated whether or not melatonin and DHEA could prevent $IL-1{\beta}$ production that is induced by anthrax lethal toxin in mouse peritoneal macrophages. Treatment of melatonin or DHEA alone, as well as together, prevented the production of $IL-1{\beta}$ caused by anthrax lethal toxin. We found that melatonin at a concentration of $10^{-6}-10^{-7}$ M inhibits $IL-1{\beta}$ production induced by anthrax lethal toxin. As expect, treatment of DHEA at a concentration $10^{-6}-10^{-7}$ M also suppressed production of $IL-1{\beta}$ by lethal toxin stimulated macrophages. The results of these studies suggest that melatonin and DHEA, immunomodulators, may have an important role in reducing the increase of cytokine production in anthrax lethal toxin-treated macrophages.

• Animal Bioscience
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• v.37 no.6
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• pp.1007-1020
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• 2024

Objective: We increased the nuclear maturation rate of antral follicle derived oocytes by using a pre-in vitro maturation (IVM) culture system and improved the developmental potential of these porcine pathenotes by supplementing with melatonin. Furthermore, we investigated the expression patterns of genes involved in cumulus expansion (HAS2, PTGS2, TNFAIP6, and PTX3) derived from small and medium antral follicles before and after oocyte maturation. Methods: Only the cumulus oocyte-complexes (COCs) derived from small antral follicles were induced with [Pre-SF(+)hCG] or without [Pre-SF(-)hCG] the addition of human chorionic gonadotropin (hCG) during the last 7 h of the pre-IVM period before undergoing the regular culture system. The mature oocytes were investigated on embryonic development after parthenogenetic activation (PA). Melatonin (10^-7 M) was supplemented during in vitro culture (IVC) to improve the developmental potential of these porcine pathenotes. Results: A pre-IVM culture system with hCG added during the last 7 h of the pre-IVM period [Pre-SF(+)hCG] effectively supported small antral follicle-derived oocytes and increased their nuclear maturation rate. The oocytes derived from medium antral follicles exhibited the highest nuclear maturation rate in a regular culture system. Compared with oocytes cultured in a regular culture system, those cultured in the pre-IVM culture system exhibited considerable overexpression of HAS2, PTGS2, and TNFAIP6. Porcine embryos treated with melatonin during IVC exhibited markedly improved quality and developmental competence after PA. Notably, melatonin supplementation during the IVM period can reduce and increase the levels of intracellular reactive oxygen species (ROS) and glutathione (GSH), respectively. Conclusion: Our findings indicate that the Pre-SF(+)hCG culture system increases the nuclear maturation rate of small antral follicle-derived oocytes and the expression of genes involved in cumulus expansion. Melatonin supplementation during IVC may improve the quality and increase the blastocyst formation rate of porcine embryos. In addition, it can reduce and increase the levels of ROS and GSH, respectively, in mature oocytes, thus affecting subsequent embryos.