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1.
Is dietary melatonin supplementation a viable adjunctive therapy for chronic periodontitis?-A randomized controlled clinical trial.
El-Sharkawy, H, Elmeadawy, S, Elshinnawi, U, Anees, M
Journal of periodontal research. 2019;(2):190-197
Abstract
BACKGROUND AND OBJECTIVE Melatonin is synthesized naturally by pineal gland and responsible for regulation of sleep/waking cycle. It showed appreciated anti-inflammatory and antioxidant properties. The aim of this randomized clinical trial (RCT) was to assess the additive effect of melatonin supplementation in insomniac individuals with generalized chronic periodontitis (gCP) after scaling and root planing (SRP). MATERIAL AND METHODS Seventy-four gCP patients with primary insomnia participated in this 6-month RCT and randomized into two groups. Melatonin group included 38 patients who were subjected to SRP with a 2-month regimen of 10 mg oral melatonin capsule once daily before bedtime. In the control group, SRP was performed for 36 participants provided with matching placebo capsules. The primary treatment outcome was the measurement of clinical attachment level gain (CAL gain) after 3 and 6 months of therapy, whereas the measurements of pocket depth reduction (PD reduction), bleeding on probing (BOP %), and the changes in salivary TNF-α levels and Athens insomnia scale (AIS) scores represented the secondary endpoints. RESULTS Melatonin group showed significantly greater CAL gain and PD reduction measurements compared to the control group at 3 and 6 months of therapy, P < 0.01. Likewise, salivary TNF-α levels and AIS scores were significantly lower in the melatonin group compared to placebo group. BOP% improved significantly in both groups without any difference. However, salivary TNF-α levels exhibited no correlation with other clinical variables in both melatonin and placebo groups. CONCLUSION Daily dietary 10 mg of melatonin supplementation might serve as a viable adjunct to SRP that yielded significantly greater CAL gain and PD reduction and lower salivary TNF-α levels and AIS scores in gCP patients with primary insomnia.
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2.
The effects of melatonin on neurohormonal regulation in cardiac cachexia: A mechanistic review.
Jafari-Vayghan, H, Saleh-Ghadimi, S, Maleki, V, Moludi, J, Alizadeh, M
Journal of cellular biochemistry. 2019;(10):16340-16351
Abstract
Heart failure (HF) is one of the prominent health concerns and its morbidity is comparable to many malignancies. Cardiac cachexia (CC), characterized by significant weight loss and muscle wasting, frequently occurs in progressive stage of HF. The pathophysiology of CC is multifactorial including nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic/catabolic imbalance. Neurohormones are critically involved in the development of both HF and CC. Melatonin is known as an anti-inflammatory and antioxidant hormone. It seems that melatonin possibly regulates the neurohormonal signaling pathway related to muscle wasting in CC, but limited comprehensive data is available on the mechanistic aspects of its activity. In this, we reviewed the reports regarding the role of neurohormones in CC occurrence and possible activity of melatonin in modulation of HF and subsequently CC via neurohormonal regulation. In addition, we have discussed proposed mechanisms of action for melatonin considering its possible interactions with neurohormones. In conclusion, melatonin likely regulates the signaling pathways related to muscle wasting in CC by reducing tumor necrosis factor α levels and activating the gene expression of insulin-like growth factor-1. Also, this hormone inhibits the proteolytic pathway by inhibiting nuclear factor-κB (NF-κB), renin-angiotensin system and forkhead box protein O1 pathways and could increase protein synthesis by activating Akt and mammalian target of rapamycin. To elucidate the positive role of melatonin in CC and exact mechanisms related to muscle wasting more cellular and clinical trial studies are needed.
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3.
Potential use of melatonin in skin cancer treatment: A review of current biological evidence.
Pourhanifeh, MH, Mahdavinia, M, Reiter, RJ, Asemi, Z
Journal of cellular physiology. 2019;(8):12142-12148
Abstract
Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.
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4.
Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells.
Juybari, KB, Hosseinzadeh, A, Ghaznavi, H, Kamali, M, Sedaghat, A, Mehrzadi, S, Naseripour, M
Current pharmaceutical design. 2019;(28):3057-3073
Abstract
Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.
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5.
The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.
Ghaderi, A, Banafshe, HR, Mirhosseini, N, Motmaen, M, Mehrzad, F, Bahmani, F, Aghadavod, E, Mansournia, MA, Reiter, RJ, Karimi, MA, et al
Addiction biology. 2019;(4):754-764
Abstract
This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (β -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (β -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (β 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (β -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (β -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (β 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (β -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (β -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (β -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.
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6.
The effect of melatonin supplementation on lipid profile and anthropometric indices: A systematic review and meta-analysis of clinical trials.
Loloei, S, Sepidarkish, M, Heydarian, A, Tahvilian, N, Khazdouz, M, Heshmati, J, Pouraram, H
Diabetes & metabolic syndrome. 2019;(3):1901-1910
Abstract
BACKGROUND Epidemiological evidence suggests that melatonin has some effects on the serum lipid. However, these results are controversial. The aim of this systematic review and meta-analysis is to examine the effect of melatonin supplement on dyslipidemia and anthropometric indices. METHODS We searched electronic databases including Medline, Embase, Scopus, Web of Science and Cochrane Library up to Des 2018 without any language restriction. To compare the effects of melatonin with placebo, differences in standardized means difference (SMD) with 95% confidence intervals (95% CI) were pooled using random effects model. RESULTS Twelve trials including 641 participants included in meta-analysis finally. The dose of melatonin was reported at 0.8-30 mg. Comparing with the control group, melatonin may improve low density lipoprotein cholesterol (LDL-C) (-0.31 mmol/L, 95% CI (-0.61, 0.01), P = 0.049, I2 = 42%) and triglyceride (TG) level (SMD = -0.45 mmol/L; 95% CI, -0.77, -0.13, P = 0.006, I2 = 47%). No significant effect of melatonin on high density lipoprotein cholesterol (HDL-C) and anthropometric indices was found. CONCLUSIONS The results of our systematic review and Meta-analyzes showed that supplementation of melatonin could be effective in improving lipid parameters and should be considered in the prevention of cardiovascular disease, although the effect of this supplement on anthropometric indices needs further investigation.
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7.
Melatonin and Caffeine Supplementation Used, Respectively, as Protective and Stimulating Agents in the Cryopreservation of Human Sperm Improves Survival, Viability, and Motility after Thawing compared to Traditional TEST-Yolk Buffer.
Pariz, JR, Ranéa, C, Monteiro, RAC, Evenson, DP, Drevet, JR, Hallak, J
Oxidative medicine and cellular longevity. 2019;:6472945
Abstract
Cryopreservation processes can damage spermatozoa and impair structural and functional cell characteristics. Plasma, nuclear membranes, and cellular organelles can suffer from the freeze and thaw process. This study evaluates the protective and stimulant effect of melatonin and caffeine supplementation on the functional characteristics of human spermatozoa before and after freezing. Thirty seminal samples from normozoospermic men aged 19-45 years old collected between October 2012 and May 2017 were included. Semen samples were supplemented with either 2 mM melatonin (MEL) prior to cryopreservation, 2 mM caffeine (CAF) in postthaw, or CAF and MEL (CM) in precryopreservation and postthaw, respectively. Kinetics and seminal parameters, mitochondrial activity, DNA fragmentation, and reactive oxygen species (ROS) levels were analyzed before and after cryopreservation. A significant reduction in sperm concentration, total and progressive motility, sperm kinetics, and mitochondrial activity, as well as a significant increase in DNA fragmentation and ROS production in postthaw samples compared to fresh samples, was identified. After administration of a caffeine and/or melatonin supplement, there was a significant increase in progressive motility in the CAF (p = 0.005) and CM (p = 0.048) groups, as well as mitochondrial activity in the CM group (p < 0.05). Cryopreservation has negative effects on overall sperm quality and increases ROS production. A combination of caffeine and melatonin in prefreeze and postthaw sperm samples has proven to be a very effective and simple way to improve semen quality. This will be particularly useful for initial low-quality semen samples, those which suffer the most from the freezing/thawing process.
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8.
Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.
Chuffa, LGA, Lupi, LA, Cucielo, MS, Silveira, HS, Reiter, RJ, Seiva, FRF
International journal of molecular sciences. 2019;(1)
Abstract
The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the "receptivity window". Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine-placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.
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9.
Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation.
Hameed, EN, Hadi Al Tukmagi, HF, Allami, HCA
Reviews on recent clinical trials. 2019;(3):203-208
Abstract
BACKGROUND Inadequate response to Erythropoietin Stimulating Agents (ESA) despite using relatively larger doses regimen represents a potential risk factor of Cardiovascular (CV) related mortality in addition to health-care economic problems in anemic patients with Chronic Kidney Disease (CKD). Erythropoietin (EPO) hyporesponsiveness related to inflammation has been increased progressively. Melatonin is well known as a potent anti-inflammatory agent. Therefore, the current study was designed to evaluate whether melatonin could improve anemic patients response to EPO. METHODS This single controlled clinical study was carried out in 41 CKD patients with hemoglobin (Hb) levels less than 11g/dl divided randomly in a 1:1 ratio into 2 groups; treatment group who received 5mg melatonin plus their regular treatments and control group who received their regular treatments only. Hematological and iron status parameters include Hb level, serum iron (S. iron), Transferrin Saturation Ratio (TSAT) and serum ferritin (S. ferritin) in addition to inflammatory parameters that include tissue necrotic factor alfa (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) determined before and after 12 weeks of treatment. RESULTS Melatonin remarkably increases the Hb level with a significant increase in S. iron and TSAT compared to baseline. The elevation of S. iron and TSAT was significantly higher in the melatonin group. Additionally, all inflammatory markers estimated were reduced significantly by melatonin compared to base line and control group. CONCLUSION The results of the current study showed that melatonin has an advantageous effect on improving EPO response in anemic patients with CKD.
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10.
Characterizing the temporal Dynamics of Melatonin and Cortisol Changes in Response to Nocturnal Light Exposure.
Rahman, SA, Wright, KP, Lockley, SW, Czeisler, CA, Gronfier, C
Scientific reports. 2019;(1):19720
Abstract
We studied the dynamics of melatonin suppression and changes in cortisol levels in humans in response to light exposure at night using high-frequency blood sampling. Twenty-one young healthy participants were randomized to receive either intermittent bright (~9,500 lux) light (IBL), continuous bright light (CBL) or continuous dim (~1 lux) light (VDL) for 6.5 h during the biological night (n = 7 per condition). Melatonin suppression occurred rapidly within the first 5 min and continued until the end of each IBL stimuli (t1/2 = ~13 min). Melatonin recovery occurred more slowly between IBL stimuli (half-maximal recovery rate of ~46 min). Mean melatonin suppression (~40%) and recovery (~50%) were similar across IBL stimuli. Suppression dynamics under CBL were also rapid (t1/2 = ~18 min), with no recovery until the light exposure ended. There was a significant linear increase of cortisol levels between the start and end of each IBL stimulus. Under CBL conditions cortisol showed trimodal changes with an initial linear activating phase, followed by an exponential inhibitory phase, and a final exponential recovery phase. These results show that light exposure at night affects circadian driven hormones differently and that outcomes are influenced by the duration and pattern of light exposure.