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European Heart Journal. Cardiovascular... Oct 2016Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release... (Review)
Review
Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release into the circulation is stimulated by the onset of darkness, followed by a progressive decrease in blood levels with the onset of dawn. Melatonin administration can maintain the quality of sleep and help to counteract age-induced cognitive decline. Melatonin can also limit the severity of a variety of cardiovascular and cerebrovascular diseases, diabetes, and cancer.
Topics: Animals; Antioxidants; Coronary Disease; Humans; Melatonin
PubMed: 27533945
DOI: 10.1093/ehjcvp/pvv037 -
Methods in Molecular Biology (Clifton,... 2022The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. The rhythm in the major urinary metabolite of...
The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. The rhythm in the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), is highly correlated with plasma melatonin and provides a noninvasive method to measure circadian phase, particularly in field-based studies. In this chapter, we describe the protocol for collecting urinary aMT6s and the method used to calculate the acrophase, or peak, time as a circadian phase marker.
Topics: Biomarkers; Circadian Rhythm; Humans; Melatonin; Urinary Tract
PubMed: 36180673
DOI: 10.1007/978-1-0716-2593-4_4 -
Journal of Ovarian Research Jun 2016Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage... (Meta-Analysis)
Meta-Analysis Review
Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting.
Topics: Animals; Antioxidants; Apoptosis; Female; Graft Survival; Humans; Melatonin; Neovascularization, Physiologic; Organ Transplantation; Ovary; Oxidative Stress
PubMed: 27287621
DOI: 10.1186/s13048-016-0245-8 -
Critical Reviews in Oncology/hematology Feb 2018The 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... (Review)
Review
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.
Topics: Animals; Breast Neoplasms; Female; Humans; Melatonin; Prospective Studies; Signal Transduction
PubMed: 29458781
DOI: 10.1016/j.critrevonc.2017.12.018 -
Physiology & Behavior Aug 2022Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of... (Review)
Review
Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of melatonin, or its important analogue, agomelatine, on depression. In this review study, we aimed to discuss the potential mechanisms of melatonin involved in the treatment of depression. It was noted that disrupted circadian rhythm can lead to depressive state, and melatonin via regulating circadian rhythm shows a therapeutic effect. It was also noted that melatonin induces antidepressant effects via promoting antioxidant system and neurogenesis, and suppressing oxidative stress, neuroinflammation, and apoptosis. The interaction effect between melatonin or agomelatine and serotonergic signaling has a significant effect on depression. It was noted that the psychotropic effects of agomelatine are induced by the synergistic interaction between melatonin and 5-HT receptors. Agomelatine also interacts with glutamatergic signaling in brain regions involved in regulating mood and circadian rhythm. Interestingly, it was concluded that melatonin exerts both pro- and anti-inflammatory effects, depending on the grade of inflammation. It was suggested that synergistic interaction between melatonin and 5-HT receptors may be able to induce therapeutic effects on other psychiatric disorders. Furthermore, dualistic role of melatonin in regulating inflammation is an important point that can be examined at different levels of inflammation in animal models of depression.
Topics: Animals; Antidepressive Agents; Depression; Humans; Inflammation; Melatonin; Serotonin
PubMed: 35504318
DOI: 10.1016/j.physbeh.2022.113835 -
Cellular and Molecular Life Sciences :... Nov 2017Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major... (Review)
Review
Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole's protective actions. Melatonin's mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.
Topics: Animals; Antioxidants; Biological Transport; Free Radicals; Humans; Melatonin; Mitochondria
PubMed: 28828619
DOI: 10.1007/s00018-017-2616-8 -
Revista Da Associacao Medica Brasileira... 2023
Topics: Humans; Female; Melatonin; Breast Neoplasms
PubMed: 37812812
DOI: 10.1590/1806-9282.697EDIT -
International Journal of Molecular... Aug 2018Melatonin exhibits extraordinary diversity in terms of its functions and distribution. When discovered, it was thought to be uniquely of pineal gland origin.... (Review)
Review
Melatonin exhibits extraordinary diversity in terms of its functions and distribution. When discovered, it was thought to be uniquely of pineal gland origin. Subsequently, melatonin synthesis was identified in a variety of organs and recently it was shown to be produced in the mitochondria. Since mitochondria exist in every cell, with a few exceptions, it means that every vertebrate, invertebrate, and plant cell produces melatonin. The mitochondrial synthesis of melatonin is not photoperiod-dependent, but it may be inducible under conditions of stress. Mitochondria-produced melatonin is not released into the systemic circulation, but rather is used primarily in its cell of origin. Melatonin's functions in the mitochondria are highly diverse, not unlike those of sirtuin 3 (SIRT3). SIRT3 is an NAD+-dependent deacetylase which regulates, among many functions, the redox state of the mitochondria. Recent data proves that melatonin and SIRT3 post-translationally collaborate in regulating free radical generation and removal from mitochondria. Since melatonin and SIRT3 have cohabitated in the mitochondria for many eons, we predict that these molecules interact in many other ways to control mitochondrial physiology. It is predicted that these mutual functions will be intensely investigated in the next decade and importantly, we assume that the findings will have significant applications for preventing/delaying some age-related diseases and aging itself.
Topics: Aging; Animals; Humans; Melatonin; Mitochondria; Models, Molecular; Oxidative Phosphorylation; Oxidative Stress; Reactive Oxygen Species; Sirtuin 3
PubMed: 30126181
DOI: 10.3390/ijms19082439 -
International Journal of Molecular... May 2021Neonatal encephalopathy is a leading cause of morbidity and mortality worldwide. Although therapeutic hypothermia (HT) is now standard practice in most neonatal... (Review)
Review
Neonatal encephalopathy is a leading cause of morbidity and mortality worldwide. Although therapeutic hypothermia (HT) is now standard practice in most neonatal intensive care units in high resource settings, some infants still develop long-term adverse neurological sequelae. In low resource settings, HT may not be safe or efficacious. Therefore, additional neuroprotective interventions are urgently needed. Melatonin's diverse neuroprotective properties include antioxidant, anti-inflammatory, and anti-apoptotic effects. Its strong safety profile and compelling preclinical data suggests that melatonin is a promising agent to improve the outcomes of infants with NE. Over the past decade, the safety and efficacy of melatonin to augment HT has been studied in the neonatal piglet model of perinatal asphyxia. From this model, we have observed that the neuroprotective effects of melatonin are time-critical and dose dependent. Therapeutic melatonin levels are likely to be 15-30 mg/L and for optimal effect, these need to be achieved within the first 2-3 h after birth. This review summarises the neuroprotective properties of melatonin, the key findings from the piglet and other animal studies to date, and the challenges we face to translate melatonin from bench to bedside.
Topics: Animals; Brain Diseases; Humans; Hypothermia, Induced; Infant, Newborn; Infant, Newborn, Diseases; Melatonin; Neuroprotection; Neuroprotective Agents
PubMed: 34067448
DOI: 10.3390/ijms22115481 -
Cellular and Molecular Neurobiology Jan 2020Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD,... (Review)
Review
Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters. Preclinical and clinical studies have shown that melatonin supplementation is an appropriate therapy for PD. Administration of melatonin leads to inhibition of some pathways related to apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and dopamine loss in PD. In addition, melatonin improves some nonmotor symptom in patients with PD. Limited studies, however, have evaluated the role of melatonin on molecular mechanisms and clinical symptoms in PD. This review summarizes what is known regarding the impact of melatonin on PD in preclinical and clinical studies.
Topics: Animals; Apoptosis; Autophagy; Disease Models, Animal; Humans; Melatonin; Oxidative Stress; Parkinson Disease
PubMed: 31388798
DOI: 10.1007/s10571-019-00720-5