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International Journal of Molecular... Apr 2023Melatonin, an endogenous hormone mainly released at night by the pineal gland, has multifaceted biofunctions. Emerging evidence points to melatonin having a crucial role... (Review)
Review
Melatonin, an endogenous hormone mainly released at night by the pineal gland, has multifaceted biofunctions. Emerging evidence points to melatonin having a crucial role in kidney health and disease. As the prevalence of chronic kidney disease (CKD) is still rising, a superior strategy to advance global kidney health is needed to not just treat CKD, but prevent it early on. Adult kidney disease can have its origins in early life. This review aims to evaluate the recent literature regarding melatonin's effect on kidney development, its clinical uses in the early stage of life, animal models documenting preventive applications of melatonin on offspring's kidney-related disease, and a thorough summary of therapeutic considerations concerning melatonin supplementation.
Topics: Animals; Melatonin; Kidney; Pineal Gland; Renal Insufficiency, Chronic; Models, Animal; Circadian Rhythm
PubMed: 37175813
DOI: 10.3390/ijms24098105 -
Fertility and Sterility Jul 2009To summarize the role of melatonin in the physiology and pathophysiology of the ovary. (Review)
Review
OBJECTIVE
To summarize the role of melatonin in the physiology and pathophysiology of the ovary.
DESIGN
Review of literature.
SETTING
University Health Science Center.
RESULT(S)
Melatonin plays an essential role in the pathogenesis of many reproductive processes. Human preovulatory follicular fluid (FF) contains higher concentrations of melatonin than does plasma, and melatonin receptors are present in ovarian granulosa cells (GC). Melatonin has been shown to have direct effects on ovarian function. Reactive oxygen species and apoptosis are involved in a number of reproductive events including folliculogenesis, follicular atresia, ovulation, oocyte maturation, and corpus luteum (CL) formation. Melatonin and its metabolites are powerful antioxidants; the primitive and primary function of melatonin may be its actions as a receptor-independent free radical scavenger and a broad-spectrum antioxidant. A large amount of scientific evidence supports a local role of melatonin in the human reproductive processes. The indole also has potential roles in the pathophysiology of endometriosis, polycystic ovary syndrome (PCOS), and premature ovarian failure (POF).
CONCLUSION(S)
We summarize the current understanding of melatonin's essential functions in the human ovary. Melatonin could become an important medication for improving ovarian function and oocyte quality, and open new opportunities for the management of several ovarian diseases.
Topics: Animals; Corpus Luteum; Female; Follicular Fluid; Granulosa Cells; Humans; Melatonin; Oocytes; Ovarian Follicle; Ovary; Receptors, Melatonin; Rodentia
PubMed: 18804205
DOI: 10.1016/j.fertnstert.2008.05.016 -
Molecules (Basel, Switzerland) Jun 2021The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter,... (Review)
Review
The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.
Topics: Animals; Circadian Rhythm; Drug Carriers; Drug Delivery Systems; Humans; Melatonin; Nanoparticles; Nanostructures; Pineal Gland
PubMed: 34200947
DOI: 10.3390/molecules26123562 -
British Journal of Pharmacology Aug 2018Melatonin, discovered in 1958 in the bovine pineal tissue, is an indoleamine that modulates circadian rhythms and has a wide variety of other functions. Haematological... (Review)
Review
Melatonin, discovered in 1958 in the bovine pineal tissue, is an indoleamine that modulates circadian rhythms and has a wide variety of other functions. Haematological neoplasms are the leading cause of death in children and adolescents throughout the world. Research has demonstrated that melatonin is a low-toxicity protective molecule against experimental haematological neoplasms, but the mechanisms remain poorly defined. Here, we provide an introduction to haematological neoplasms and melatonin, especially as they relate to the actions of melatonin on haematological carcinogenesis. Secondly, we summarize what is known about the mechanisms of action of melatonin in the haematological system, including its pro-apoptotic, pro-oxidative, anti-proliferative and immunomodulatory actions. Thirdly, we discuss the advantages of melatonin in combination with other drugs against haematological malignancy, as well as its other benefits on the haematological system. Finally, we summarize the findings that are contrary to the suppressive effects of melatonin on cancers of haematological origin. We hope that this information will be helpful in the design of studies related to the therapeutic efficacy of melatonin in haematological neoplasms. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.
Topics: Animals; Antineoplastic Agents; Hematologic Neoplasms; Humans; Melatonin
PubMed: 28880375
DOI: 10.1111/bph.13966 -
The Journal of Investigative Dermatology Mar 2018Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although... (Review)
Review
Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although melatonin is best known to regulate circadian rhythmicity and lower vertebrate skin pigmentation, the full spectrum of functional activities of this free radical-scavenging molecule, which also induces/promotes complex antioxidative and DNA repair systems, includes immunomodulatory, thermoregulatory, and antitumor properties. Because this plethora of functional melatonin properties still awaits to be fully appreciated by dermatologists, the current review synthesizes the main features that render melatonin a promising candidate for the management of several dermatoses associated with substantial oxidative damage. We also review why melatonin promises to be useful in skin cancer prevention, skin photo- and radioprotection, and as an inducer of repair mechanisms that facilitate the recovery of human skin from environmental damage. The fact that human skin and hair follicles not only express functional melatonin receptors but also engage in substantial, extrapineal melatonin synthesis further encourages one to systematically explore how the skin's melatonin system can be therapeutically targeted in future clinical dermatology and enrolled for preventive medicine strategies.
Topics: Animals; Antineoplastic Agents; Hair Follicle; Humans; Melatonin; Radiation-Protective Agents; Receptors, Melatonin; Skin; Skin Neoplasms; Skin Pigmentation; Wound Healing
PubMed: 29428440
DOI: 10.1016/j.jid.2017.10.025 -
Cells Nov 2022Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on...
Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.
Topics: Humans; Mice; Animals; Glioblastoma; Melatonin; Glycolysis; Cell Division; Hydrogen-Ion Concentration
PubMed: 36359862
DOI: 10.3390/cells11213467 -
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 -
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 -
Frontiers in Bioscience (Landmark... Jan 2013Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and... (Review)
Review
Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.
Topics: Animals; Blood Pressure; Circadian Rhythm; Darkness; Hypertension; Light; Melatonin; Pineal Gland; Rats
PubMed: 23276947
DOI: 10.2741/4125 -
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