-
1.
Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed.
Kleszczyński, K, Slominski, AT, Steinbrink, K, Reiter, RJ
Nutrients. 2020;(9)
Abstract
The recent pandemic of COVID-19 has already infected millions of individuals and has resulted in the death of hundreds of thousands worldwide. Based on clinical features, pathology, and the pathogenesis of respiratory disorders induced by this and other highly homogenous coronaviruses, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response contribute to COVID-19 pathology; these are caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This leads to a cytokine storm and subsequent progression triggering acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), and often death. We and others have reported melatonin to be an anti-inflammatory and anti-oxidative molecule with a high safety profile. It is effective in critical care patients by reducing their vascular permeability and anxiety, inducing sedation, and improving their quality of sleep. As melatonin shows no harmful adverse effects in humans, it is imperative to introduce this indoleamine into clinical trials where it might be beneficial for better clinical outcomes as an adjuvant treatment of COVID-19-infected patients. Herein, we strongly encourage health care professionals to test the potential of melatonin for targeting the COVID-19 pandemic. This is urgent, since there is no reliable treatment for this devastating disease.
-
2.
Integrative considerations during the COVID-19 pandemic.
Alschuler, L, Weil, A, Horwitz, R, Stamets, P, Chiasson, AM, Crocker, R, Maizes, V
Explore (New York, N.Y.). 2020;(6):354-356
-
3.
Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment.
Martín Giménez, VM, Inserra, F, Tajer, CD, Mariani, J, Ferder, L, Reiter, RJ, Manucha, W
Life sciences. 2020;:117808
-
-
Free full text
-
Abstract
COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.
-
4.
Melatonin: A promising agent targeting leukemia.
Shafabakhsh, R, Mirzaei, H, Asemi, Z
Journal of cellular biochemistry. 2020;(4):2730-2738
Abstract
Leukemia or cancer of blood is a well-known cancer, which affects a range of people from newborns to the very old. It is a public health problem throughout the world. By way of treatment, due to the lack of specific anticancer therapies, common treatments of leukemia lead to severe side effects. Nonspecific anticancer drugs result in inhibition of normal cell growth and thereby their necrosis. Moreover, drug resistance is an additional problem, which stands in the way of leukemia treatment. Thus, finding new treatments for leukemia is essential. Melatonin, as a natural product, has been shown to be effective in a wide variety of diseases such as coronary heart disease, schizophrenia, chronic pain, and Alzheimer's disease. In addition, melatonin levels have been observed to be altered in different cancers, such as breast cancer, colorectal cancer endometrial cancer, and hematopoetical cancers. Anticancer features of melatonin such as pro-oxidation, apoptosis induction, antiangiogenesis property and metastasis and invasion inhibition suggest that this natural compound can be used as a potential agent in novel therapeutic strategies for cancers. Also, it has been reported that melatonin has positive and protective effects on different physiological reactions and in normal bone marrow cells suggesting effectiveness in leukemia therapy. Thus, the aim of our paper was to depict and summarize the main molecular targets of melatonin on leukemia models.
-
5.
Melatonergic agents in the prevention of delirium: A network meta-analysis of randomized controlled trials.
Yang, CP, Tseng, PT, Pei-Chen Chang, J, Su, H, Satyanarayanan, SK, Su, KP
Sleep medicine reviews. 2020;:101235
Abstract
Disruption of the sleep-wake cycle is a risk factor and a prodromal indicator of delirium. Melatonergic agents may thus play a role in the prevention of delirium. Based upon literature search on eight databases, this systemic review and frequentist model network meta-analysis (NMA) aimed to determine the efficacy and tolerability of melatonergic agents in delirium prevention. Six randomized controlled trials (RCTs) were included with a total of 913 adult participants (mean age = 78.8, mean female proportion = 59.4%) investigating the preventive effects of melatonergic agents in patients with high risks of developing delirium. The outcomes of NMA demonstrated significant preventive effects with 5 mg/day of melatonin [Odds Ratio (OR) = 0.21, 95% Confidence Intervals (CIs): 0.07 to 0.64], melatonin (0.5 mg/d) [OR = 0.16 (95% CIs: 0.03 to 0.75)], and ramelteon (8 mg/d) [OR = 0.28 (95% CIs: 0.12 to 0.65)] against placebo groups. According to the surface under the cumulative ranking curve (SUCRA), 0.5 mg/d of melatonin was associated with the best preventive effect. Our findings provided the rationale for recommending low-dose melatonergic agents for delirium prevention in the practice guidelines.
-
6.
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.
-
7.
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.
-
8.
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.
-
9.
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.
-
10.
Melatonin: A New Plant Hormone and/or a Plant Master Regulator?
Arnao, MB, Hernández-Ruiz, J
Trends in plant science. 2019;(1):38-48
Abstract
Melatonin is a pleiotropic molecule with many diverse actions in plants. It is considered primarily an antioxidant with important actions in the control of reactive oxygen and nitrogen species (ROS and RNS), among other free radicals, and harmful oxidative molecules present in plant cells. In addition, plant melatonin is involved in multiple physiological actions, such as growth, rooting, seed germination, photosynthesis, and protection against abiotic and/or biotic stressors. The recent identification of the first plant melatonin receptor opened the door to this regulatory molecule being considered a new plant hormone. However, due to the diversity of its actions, melatonin has also been proposed as a plant master regulator. Here, we discuss the most recent data in respect to both perspectives.