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Song Y, Yoon M. Melatonin effects on animal behavior: circadian rhythm, stress response, and modulation of behavioral patterns. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2025; 67:1-16. [PMID: 39974791 PMCID: PMC11833209 DOI: 10.5187/jast.2024.e105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 09/26/2024] [Accepted: 10/29/2024] [Indexed: 02/21/2025]
Abstract
Melatonin plays a crucial role in various behavioral and physiological aspects of animals, including regulating their circadian rhythms. This review provides a comprehensive evaluation of the multifaceted effects of melatonin on animal behavior, such as temperament, stress, and aggression regulation. The focus is on the complex interactions between melatonin and the hormonal and neurotransmitter systems, highlighting how melatonin interacts with cortisol, serotonin, and dopamine to influence behavior. Additionally, it investigates the effects of melatonin on the hypothalamic-pituitary-gonada (HPG) axis and stress responses, emphasizing its potential to improve stress management and social interactions, thereby enhancing animal welfare. The review also examines the seasonal variations of melatonin and its impact on aggression and reproductive activities related to photoperiods, as well as its effects on learning and memory to suggest improvements in animal training methods and practices. Furthermore, it discusses the influence of melatonin on appetite and physical activity regulation, implying its involvement in metabolic processes. In conclusion, further research is needed to elucidate the complex mechanisms underlying the extensive influence of melatonin on animal behavior. Through this review, the aim is to integrate the overall knowledge about melatonin and animal behavioral temperament and to propose new research areas for animal management based on behavioral and hormonal regulation.
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Affiliation(s)
- Yubin Song
- Department of Animal Science and
Biotechnology, Kyungpook National University, Sangju 37224,
Korea
| | - Minjung Yoon
- Department of Animal Science and
Biotechnology, Kyungpook National University, Sangju 37224,
Korea
- Department of Horse, Companion and Wild
Animal Science, Kyungpook National University, Sangju 37224,
Korea
- Research Institute for Innovative Animal
Science, Kyungpook National University, Sangju 37224,
Korea
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2
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Vanga MK, Bhukya R, Thumma V, Tamalapakula V, Boddu LS, Manga V. Antioxidant and Antimicrobial Activities of 4H-Chromene Based Indole-Pyrimidine Hybrids: Synthesis and Molecular Docking Studies. Chem Biodivers 2024; 21:e202401583. [PMID: 39133616 DOI: 10.1002/cbdv.202401583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/12/2024] [Indexed: 10/11/2024]
Abstract
A series of 4H-Chromene Based Indole-Pyrimidine Hybrids synthesized using simple and efficient multicomponent reaction. The title molecules were evaluated for their invitro antioxidant and antimicrobial activities. Compounds 8 g containing bromo substituted naphthalene displayed potent antioxidant activity with IC50 value of 1.09±0.34 μM and 1.10±0.36 μM. Compound 10 a, a 4-methylphenyl derivative presented potent activity with antioxidant activity with IC50 value of 1.29±0.35 μM and 1.43±0.38 μM. Subsequently, compounds 8 a, 8 b, 8 d and 10 g had shown prominent percentage of inhibition and derived effective IC50 values in comparison to reference drug Ascorbic Acid. The invitro antimicrobial activity carried out against two gram positive and two gram-negative bacteria, and two fungal strains using Ampicillin and Itraconazole as refence drugs. Compound 10 f exhibited exceptional efficacy against all types of bacterial and fungal strains compared to Ampicillin and Itraconazole, compounds 8 e and 8 g showed activity against bacterial strains whereas compound 10 g exhibited the most effective zone of inhibition against fungal strains. The molecular docking study against crystal structure of NADPH oxidase obtained supporting docking scores and showed notable binding interactions such as H-bond and hydrophobic.
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Affiliation(s)
- Murali Krishna Vanga
- Department of Chemistry, Osmania University, Hyderabad, 500007, Telangana, India
| | - Rambabu Bhukya
- Department of Chemistry, Osmania University, Hyderabad, 500007, Telangana, India
| | - Vishnu Thumma
- Department of Sciences and Humanities, Matrusri Engineering College, Hyderabad, 500059, Telangana, India
| | - Vani Tamalapakula
- University College of Technology, Osmania University, Hyderabad, Telangana, 500007, India
| | - Lakshmi Satya Boddu
- Department of Pharmaceutics, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Telangana, 502313, India
| | - Vijjulatha Manga
- Department of Chemistry, Osmania University, Hyderabad, 500007, Telangana, India
- Telangana Mahila Viswavidyalayam, Hyderabad, Hyderabad, Telangana, 500095, India
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3
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Cardenas-Padilla AJ, Jimenez-Trejo F, Cerbon M, Medrano A. The Role of Melatonin on Caprine ( Capra hircus) Sperm Freezability: A Review. Antioxidants (Basel) 2024; 13:1466. [PMID: 39765795 PMCID: PMC11673025 DOI: 10.3390/antiox13121466] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/23/2024] [Accepted: 11/27/2024] [Indexed: 01/11/2025] Open
Abstract
In mammals, the pineal hormone melatonin is the most powerful pacemaker of the master circadian clock and is responsible for reproduction in seasonal breeders. It is also well known that melatonin and its metabolites play antioxidant roles in many tissues, including reproductive cells. Melatonin synthesis and secretion from the pineal gland occurs during scotophase (the dark phase during a day-night cycle), while its inhibition is observed during photophase (period of light during a day-night cycle). Short-day breeders, such as goats, are stimulated to breed in a manner dependent on high endogenous levels of melatonin. This hormone can be synthesized in various extra-pineal tissues, such as retina, gastrointestinal tract, ovaries, and testis, with its main function being as a local antioxidant, given that melatonin and its metabolites are potent scavengers of reactive oxygen and nitrogen species. Moreover, it has been reported that some functions of melatonin can be exerted through plasma membrane and intracellular receptors expressed in the male reproductive system, including germ cells, immature and mature spermatozoa. It has been shown that melatonin may enhance gamete cryosurvival mainly by its addition into the media and/or in exogenous melatonin treatments in several species. In the present review, the physiological effects of endogenous melatonin in mammals are described, with a deeper focus on caprine reproduction. Additionally, results from recent investigations on the roles of exogenous melatonin aimed at improving the reproductive efficiency of goat bucks are discussed. There are contradictory findings and a limited amount of research available in the field of goat sperm cryopreservation associated with the use of melatonin. Understanding and improving goat reproduction and production is essential for many marginalized human populations around the world who directly depend on goats to maintain and improve their lifestyle.
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Affiliation(s)
- Alberto Jorge Cardenas-Padilla
- Laboratorio de Reproducción Animal, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de Mexico, Cuautitlán Izcalli 54714, Mexico;
| | | | - Marco Cerbon
- Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de Mexico, Coyoacán, Mexico City 04510, Mexico;
| | - Alfredo Medrano
- Laboratorio de Reproducción Animal, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de Mexico, Cuautitlán Izcalli 54714, Mexico;
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Comai S, Gobbi G. Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views. J Pineal Res 2024; 76:e13011. [PMID: 39400423 DOI: 10.1111/jpi.13011] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/15/2024]
Abstract
Sleep, constituting approximately one-third of the human lifespan, is a crucial physiological process essential for physical and mental well-being. Normal sleep consists of an orderly progression through wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the "hormone of sleep," plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high-affinity G-protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders.
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Affiliation(s)
- Stefano Comai
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
- Department of Biomedical Sciences, University of Padua, Padua, Italy
- Department of Psychiatry, McGill University and McGill University Health Center, Montreal, Québec, Canada
- IRCSS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriella Gobbi
- Department of Psychiatry, McGill University and McGill University Health Center, Montreal, Québec, Canada
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Sarac Gul Y, Kose O, Altin A, Yemenoglu H, Arslan H, Akyildiz K, Yilmaz A. Melatonin supports nonsurgical periodontal treatment in patients with Type 2 diabetes mellitus and periodontitis: A randomized clinical trial. J Periodontol 2024; 95:832-841. [PMID: 38055628 DOI: 10.1002/jper.23-0335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND Diabetes mellitus (DM)-associated hyperinflammatory host response significantly provokes periodontal tissue destruction. In this context, the support of nonsurgical periodontal therapy in diabetics with host modulation agents is a current field of study. This clinical study aims to investigate the clinical efficacy of melatonin supplementation and discuss its possible biological mechanisms in nonsurgical periodontal treatment in patients with DM and periodontitis through some fundamental markers. METHODS In this randomized controlled and single-blind study, 27 of 55 diabetic patients with periodontitis (stage III/IV and grade C) underwent full-mouth scaling and root planing (fmSRP) alone and 28 patients underwent melatonin administration (6 mg daily, 30 days) in addition to fmSRP (full-mouth scaling and root planing plus melatonin, fmSRP-mel). The potential therapeutic contribution of melatonin was evaluated clinically and biochemically (gingival crevicular fluid RANKL, OPG, MMP-8, and serum IL-1β levels) at 3rd and 6th months. RESULTS Melatonin (tablet, 6 mg daily, 30 days) did not cause any local or systemic side effects. fmSRP alone resulted in significant reduction in serum IL-1β levels, pocket depths, gingival inflammation, and gingival crevicular fluid RANKL and MMP-8 levels (p < 0.05). Moreover, melatonin supplementation resulted in a more significant decrease in bleeding and pocket depth scores at probing, especially at 3 months (p < 0.05). Furthermore, RANKL and MMP-8 levels were significantly lower at 3 months and IL-1β levels at 6 months compared to the control group (p < 0.05). However, OPG levels were not affected significantly by the treatments (p > 0.05). CONCLUSION Melatonin, as a host modulation agent, significantly increases the clinical efficacy of fmSRP. The reduction in periodontal inflammation and pocket depths may be a result of marked suppression of RANKL-associated osteoclastogenesis and extracellular matrix damage by melatonin.
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Affiliation(s)
- Yagmur Sarac Gul
- School of Dentistry, Department of Periodontology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Oguz Kose
- School of Dentistry, Department of Periodontology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Ahmet Altin
- School of Dentistry, Department of Periodontology, Istanbul Kent University, Istanbul, Turkey
| | - Hatice Yemenoglu
- School of Dentistry, Department of Periodontology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Hatice Arslan
- School of Dentistry, Department of Periodontology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Kerimali Akyildiz
- School of Vocational Health Care Services, Department of Medical Services and Techniques, Recep Tayyip Erdogan University, Rize, Turkey
| | - Adnan Yilmaz
- School of Medicine, Department of Biochemistry, Recep Tayyip Erdogan University, Rize, Turkey
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Zare M, Kazempour M, Hosseini Choupani SM, Akhavan SR, Salini M, Rombenso A, Esmaeili N. The crosstalk between photoperiod and early mild stress on juvenile oscar (Astronotus ocellatus) after acute stress. FISH PHYSIOLOGY AND BIOCHEMISTRY 2024; 50:1025-1046. [PMID: 38407735 DOI: 10.1007/s10695-024-01316-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 02/04/2024] [Indexed: 02/27/2024]
Abstract
Early mild stress (EMS) is like preparedness and might help fish deal with stress appropriately. This study investigated how EMS and photoperiod changes can impact growth, haematology, blood biochemistry, immunological response, antioxidant system, liver enzymes, and stress response of oscar (Astronotus ocellatus; 7.29 ± 0.96 g) before and after acute confinement stress (AC stress). Ten experimental treatments included five different photoperiods 8L16D (08:16 light to dark), 12L12D (12:12 light to dark), 16L8D (16:08 light to dark), 20L4D (20:04 light to dark), and 24L0D (24:00 light to dark), and these five photoperiod schedules were conducted in an EMS condition. After 9 weeks, no significant differences were found in growth parameters, survival rate, and body composition. At the end of the experiment and after AC stress, fish farmed in 24 light hours had the lowest haematocrit, white blood cells, total protein, blood performance, lysozyme, immunoglobulin M, complement C3, superoxide dismutase, and catalase. Fish that experienced EMS had significantly higher survival rates than those farmed in normal conditions (80.67% vs 61.33%). In conclusion, considering all measured parameters, 8-h light can be suggested as an optimum photoperiod for this fish species. Under 24L0D (no EMS) conditions, there were many negative effects apparent. In addition, a positive effect of EMS was evident in terms of survival after AC stress. AC stress decreased some health parameters under 24-h light treatment, while these results were not observed in EMS-exposed fish. Therefore, the EMS schedule can be a useful tool in preventing the negative effects of stress.
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Affiliation(s)
- Mahyar Zare
- Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, University of South Bohemia in České Budějovice, Na Sádkách, České Budějovice, Czech Republic
| | - Mohammad Kazempour
- Department of Microbiology, Pathobiology & Basic Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
| | | | - Sobhan R Akhavan
- Nelson Marlborough Institute of Technology, 322 Hardy Street, Private Bag 19, Nelson, New Zealand
| | - Michael Salini
- Nutrition and Seafood Laboratory (NuSea.Lab), School of Life and Environmental Sciences, Deakin University, Geelong, VIC, 3225, Australia
| | - Artur Rombenso
- CSIRO, Agriculture and Food, Livestock & Aquaculture Program, Bribie Island Research Centre, Bribie Island, QLD, Australia
| | - Noah Esmaeili
- Institute for Marine and Antarctic Studies, University of Tasmania, 15-21 Nubeena Cres, Hobart, Taroona, TAS, 7053, Australia.
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Rafiyian M, Gouyandeh F, Saati M, Davoodvandi A, Rasooli Manesh SM, Asemi R, Sharifi M, Asemi Z. Melatonin affects the expression of microRNA-21: A mini-review of current evidence. Pathol Res Pract 2024; 254:155160. [PMID: 38277748 DOI: 10.1016/j.prp.2024.155160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/18/2024] [Accepted: 01/18/2024] [Indexed: 01/28/2024]
Abstract
Melatonin (MLT) is an endogenous hormone produced by pineal gland which possess promising anti-tumor effects. Anti-inflammatory and anti-oxidant properties of MLT, along with its immunomodulatory, proapoptotic, and anti-angiogenic properties, are often referred to the main mechanisms of its anti-tumor effects. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of MLT. Among these MLT-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs(miRNAs). MiRNAs are among the most promising and potential therapeutic and diagnostic tools in different diseases and enhanced the development of better therapeutic drugs. Suppression of oncomicroRNAs such as microRNA-21, - 20a, and - 27a as well as, up-regulation of microRNA-34 a/c are among the most important effects of MLT on microRNAs homeostasis. Recently, miR-21 has attracted the attention of scientists due to the its wide range of effects on different cancers and diseases. Regulation of this RNA may be a key to the development of better therapeutic targets. The present review will summarize the findings of in vitro and experimental studies of MLT-induced impacts on the expression of microRNAs which are involved in different models and numerous stages of tumor initiation, growth, metastasis, and chemo-resistance.
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Affiliation(s)
- Mahdi Rafiyian
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Farzaneh Gouyandeh
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Saati
- Department of Nursing, Semnan Branch, Islamic Azad University, Semnan, Islamic Republic of Iran
| | - Amirhossein Davoodvandi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | | | - Reza Asemi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Häusler S, Robertson NJ, Golhen K, van den Anker J, Tucker K, Felder TK. Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence? Antioxidants (Basel) 2023; 12:1630. [PMID: 37627625 PMCID: PMC10451719 DOI: 10.3390/antiox12081630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/28/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Despite significant improvements in survival following preterm birth in recent years, the neurodevelopmental burden of prematurity, with its long-term cognitive and behavioral consequences, remains a significant challenge in neonatology. Neuroprotective treatment options to improve neurodevelopmental outcomes in preterm infants are therefore urgently needed. Alleviating inflammatory and oxidative stress (OS), melatonin might modify important triggers of preterm brain injury, a complex combination of destructive and developmental abnormalities termed encephalopathy of prematurity (EoP). Preliminary data also suggests that melatonin has a direct neurotrophic impact, emphasizing its therapeutic potential with a favorable safety profile in the preterm setting. The current review outlines the most important pathomechanisms underlying preterm brain injury and correlates them with melatonin's neuroprotective potential, while underlining significant pharmacokinetic/pharmacodynamic uncertainties that need to be addressed in future studies.
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Affiliation(s)
- Silke Häusler
- Division of Neonatology, Department of Pediatrics, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
| | - Nicola J. Robertson
- EGA Institute for Women’s Health, University College London, London WC1E 6HX, UK; (N.J.R.); (K.T.)
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK
| | - Klervi Golhen
- Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4001 Basel, Switzerland; (K.G.); (J.v.d.A.)
| | - John van den Anker
- Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4001 Basel, Switzerland; (K.G.); (J.v.d.A.)
- Division of Clinical Pharmacology, Children’s National Hospital, Washington, DC 20001, USA
| | - Katie Tucker
- EGA Institute for Women’s Health, University College London, London WC1E 6HX, UK; (N.J.R.); (K.T.)
| | - Thomas K. Felder
- Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
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Contreras-Correa ZE, Messman RD, Swanson RM, Lemley CO. Melatonin in Health and Disease: A Perspective for Livestock Production. Biomolecules 2023; 13:biom13030490. [PMID: 36979425 PMCID: PMC10046399 DOI: 10.3390/biom13030490] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/21/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin’s antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.
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10
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Smajdor J, Paczosa-Bator B, Piech R. Advances on Hormones and Steroids Determination: A Review of Voltammetric Methods since 2000. MEMBRANES 2022; 12:1225. [PMID: 36557132 PMCID: PMC9782681 DOI: 10.3390/membranes12121225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/18/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
This article presents advances in the electrochemical determination of hormones and steroids since 2000. A wide spectrum of techniques and working electrodes have been involved in the reported measurements in order to obtain the lowest possible limits of detection. The voltammetric and polarographic techniques, due to their sensitivity and easiness, could be used as alternatives to other, more complicated, analytical assays. Still, growing interest in designing a new construction of the working electrodes enables us to prepare new measurement procedures and obtain lower limits of detection. A brief description of the measured compounds has been presented, along with a comparison of the obtained results.
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11
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SUZEN M, DİLAVER E, UÇKAN S. Evaluation of prevalence and dimension of Pineal Gland Calcification by cone-beam computed tomography (CBCT). CUMHURIYET DENTAL JOURNAL 2022. [DOI: 10.7126/cumudj.1111722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Abstract
Objective: This study aimed to investigate the prevalence and dimensions of pineal gland calcification using cone-beam computed tomography (CBCT) in patients undergoing dental treatment.
Materials and Methods: CBCTs that localized pineal gland in the fov range was selected in this retrospective study. The presence of pineal gland calcification (PGC) was noted. Vertical, horizontal and areal measurements were made by a single observer (M.S). Variables such as age, gender for each patient were recorded using previous clinical examination data.
Results: The prevalence of pineal gland calcification was 33.64% (female to male ratio 3:2). The difference between males and females was not significant (p>0.05). PGC was highly seen in older patients when compared with younger patients (p:000). The average vertical and horizontal dimension of PGC was 2,56±0,98mm and 3,39±1,29 mm respectively. The average total calcified area was 5,45±3,75 mm2.
Conclusion: This study did not find any correlation between age, gender, and linear measurements. However, the average calcified are in men was found to be significantly higher than in women.
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Affiliation(s)
- Muazzez SUZEN
- Istanbul Medipol University, Faculty of Dentistry, Department of Oral And Maxillofacial surgery
| | - Emrah DİLAVER
- İstanbul Medipol University,School of dentistry,Deparment of Oral and Maxillofacial Surgery
| | - Sina UÇKAN
- Istanbul Medipol University,School of dentistry,Deparment of Oral and Maxillofacial Surgery
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12
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Heidarizadi S, Rashidi Z, Jalili C, Gholami M. Overview of biological effects of melatonin on testis: A review. Andrologia 2022; 54:e14597. [PMID: 36168927 DOI: 10.1111/and.14597] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 11/29/2022] Open
Abstract
Infertility is a major global health issue and male factors account for half of all infertility cases. One of the causes of male infertility is the loss of spermatogonial stem cells, which may occur because of chemotherapy, radiotherapy or genetic defects. In numerous animal species, the evidence suggests the pineal gland and melatonin secretion in their reproductive activities are involved. Recently, considerable attention has pointed to the usage of melatonin in the treatment of diseases. Melatonin is associated with the regulation of circadian and seasonal rhythmic functions, immune system functions, retinal physiology, spermatogenesis and inhibition of tumour growth in different species. Several studies demonstrated that melatonin acts as an anti-apoptotic, anti-inflammatory, anticancer and antioxidant agent. Melatonin can also protect testicles and spermatogonia against oxidative damage, chemotherapy drugs, environmental radiation, toxic substances, hyperthermia, ischemia/reperfusion, diabetes-induced testicular damage, metal-induced testicular toxicity, improve sperm quality and it affects the testosterone secretion pathway by affecting Leydig cells. Therefore, the objective of this study is to investigate the biological effects of melatonin as a natural antioxidant on testicles and their disorders.
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Affiliation(s)
- Somayeh Heidarizadi
- Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Rashidi
- Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Cyrus Jalili
- Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammadreza Gholami
- Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Effects of Piper guineense (African Black Pepper) Seeds on Lipid Profile, Renal Function Parameters, and Antioxidant Status of Cavia porcellus. MEDICAL LABORATORY JOURNAL 2022. [DOI: 10.52547/mlj.16.5.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023] Open
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14
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Intranasally administered melatonin core-shell polymeric nanocapsules: A promising treatment modality for cerebral ischemia. Life Sci 2022; 306:120797. [PMID: 35841976 DOI: 10.1016/j.lfs.2022.120797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 11/22/2022]
Abstract
AIMS The neurohormone melatonin (MEL) has been reported as a promising neuroprotective molecule, however it suffers pharmaceutical limitations such as poor solubility and low bioavailability, which hinder its pharmacological and clinical potential. In the current work, MEL was loaded in core-shell nanocarrier system; polymeric nanocapsules (PNCs), and assessed for its potential in cerebral ischemia reperfusion injury rat model when administered intranasally. KEY FINDINGS Adopting a D-optimal factorial design, MEL-PNCs were successfully formulated using the nanoprecipitation technique. MEL-PNCs exhibited a particle size ranging from 143.5 to 444 nm, negative zeta potential values ranging from -24.2 to -38.7 mV, cumulative release % for MEL ranging from 36.79 to 41.31 % over 8 h period, with overall good storage properties. The selected MEL-PNCs formulation displayed 8-fold higher permeation than the drug solution across sheep nasal mucosa. MEL-PNCs administered intranasally decreased oxidative stress and hippocampal inflammation, and the histological examination revealed the significant restoration of hippocampal neurons. SIGNIFICANCE MEL-PNCs administered intranasally could be a promising treatment modality in brain ischemia.
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15
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Salanitro M, Wrigley T, Ghabra H, de Haan E, Hill CM, Solmi M, Cortese S. Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev 2022; 139:104723. [PMID: 35691474 DOI: 10.1016/j.neubiorev.2022.104723] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 05/20/2022] [Accepted: 06/01/2022] [Indexed: 10/18/2022]
Abstract
We conducted the first systematic review and series of meta-analyses to assess the efficacy and tolerability of melatonin in children/adolescents or adults with sleep or mental health disorders, using the same set of criteria across disorders and ages. Based on a pre-registered protocol (PROPSPERO: CRD42021289827), we searched a broad range of electronic databases up to 02.02.2021 for randomized control trials (RCTs) of melatonin. We assessed study quality using the Risk of Bias tool, v2. We included a total of 34 RCTs (21 in children/adolescents: N = 984; 13 in adults: N = 1014). We found evidence that melatonin significantly improved sleep onset latency and total sleep time, but not sleep awaking, in children and adolescents with a variety of neurodevelopmental disorders, and sleep onset latency (measured by diary) as well as total sleep time (measured with polysomnography) in adults with delayed sleep phase disorder. No evidence of significant differences between melatonin and placebo was found in terms of tolerability. We discuss clinical and research implications of our findings.
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Affiliation(s)
| | | | | | - Edward de Haan
- Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Brain & Cognition (ABC) Center, University of Amsterdam, Amsterdam, the Netherland
| | - Catherine M Hill
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Sleep Medicine, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Marco Solmi
- Department of Psychiatry, University of Ottawa, Ontario, Canada; Department of Mental Health, The Ottawa Hospital, Ontario, Canada; Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program University of Ottawa, Ottawa, Ontario; Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
| | - Samuele Cortese
- Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
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16
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Melatonin Prescribing in Assisted Living. J Am Med Dir Assoc 2022; 23:1031-1037. [PMID: 34762846 PMCID: PMC9097337 DOI: 10.1016/j.jamda.2021.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 10/11/2021] [Accepted: 10/11/2021] [Indexed: 01/25/2023]
Abstract
OBJECTIVES Aging is associated with sleep problems, which are common among assisted living (AL) residents. More than 40% of residents have insomnia, and almost 70% have a sleep disturbance of some kind. Melatonin to treat sleep disorders has become common among older adults, but its use in AL is unknown, which is concerning because melatonin may have side effects and interfere with other medications. The purpose of this study was to determine the prevalence and correlates of melatonin prescribing in AL, to inform whether changes in care may be indicated. DESIGN Cross-sectional chart abstracts and interviews. SETTINGS AND PARTICIPANTS Data were collected in 250 randomly selected AL communities among 5777 residents across 7 states in the United States and weighted to an estimated 4043 communities and 152,719 residents. METHODS Charts of residents were abstracted, and AL administrators and health care supervisors were interviewed to obtain information related to case-mix, staffing, and attitudes regarding psychoactive medications. Weighted analyses primarily examined the association of melatonin prescribing with community- and resident-level characteristics. RESULTS Melatonin was prescribed in 82% of communities, more commonly in those that had a registered nurse or licensed practical nurse on site (+7%, P = .027), and whose health care supervisor was more favorable toward nonpharmacologic practices (+18%, P = .010). On average, 9% of residents were prescribed melatonin, with prescriptions being more common among those diagnosed with dementia (+24%, P = .004); a psychiatric disorder, especially an anxiety disorder (+43%, P = .007); having behavioral expressions; and taking other psychotropics. Coprescribing was common, especially with antidepressants (OR 2.64, 95% CI 1.99, 3.48; P < .001). CONCLUSIONS AND IMPLICATIONS This study is the first to examine melatonin prescribing in AL, and finds it to be common. Such use may be appropriate if it is as a more suitable replacement for hypnotics. The fact that use varies by organizational characteristics suggests practices may be modifiable. Research examining benefits and side effects of melatonin, overall and in relation to other medications, is indicated to promote better care for AL residents.
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Liu PH, Chuang GT, Hsiung CN, Yang WS, Ku HC, Lin YC, Chen YS, Huang YY, Lin CH, Li WY, Lin JW, Hsu CN, Hwang JJ, Liao KCW, Hsieh ML, Lee HL, Shen CY, Chang YC. A genome-wide association study for melatonin secretion. Sci Rep 2022; 12:8025. [PMID: 35577822 PMCID: PMC9110427 DOI: 10.1038/s41598-022-12084-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 05/04/2022] [Indexed: 11/09/2022] Open
Abstract
AbstractMelatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.
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18
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Artificial Light at Night, Higher Brain Functions and Associated Neuronal Changes: An Avian Perspective. BIRDS 2022. [DOI: 10.3390/birds3010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In recent times, there has been an unprecedented increase in usage of electrical lightning. This has led to increase in artificial light at night (ALAN), and it has been suggested as a source of environmental pollution. ALAN exposure has been reported to be associated with disruption of daily rhythms and serious health consequences, such as immune, metabolic, and cognitive dysfunctions in both birds and mammals. Given the worldwide pervasiveness of ALAN, this research topic is also important from an ecological perspective. In birds, daily timings and appropriate temporal niches are important for fitness and survival. Daily rhythms in a wide array of functions are regulated by the circadian clock(s) and endogenous oscillators present in the body. There is accumulating evidence that exposure to ALAN disrupts clock-regulated daily rhythms and suppresses melatonin and sleep in birds. Circadian clock, melatonin, and sleep regulate avian cognitive performance. However, there is limited research on this topic, and most of the insights on the adverse effects of ALAN on cognitive functions are from behavioural studies. Nevertheless, these results raise an intriguing question about the molecular underpinning of the ALAN-induced negative consequences on brain functions. Further research should be focused on the molecular links between ALAN and cognitive performance, including the role of melatonin, which could shed light on the mechanism by which ALAN exposures lead to negative consequences.
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De Gregorio D, Comai S. Acute and Chronic Pain Preclinical Models to Study the Analgesic Properties of Melatonergic Compounds. Methods Mol Biol 2022; 2550:453-461. [PMID: 36180713 DOI: 10.1007/978-1-0716-2593-4_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G protein-coupled receptors, MT1 and MT2. MLT displays analgesic properties in several animal paradigms of acute, inflammatory, and neuropathic pain. Although the analgesic mechanism of action of MLT is not yet completely elucidated, there is strong preclinical evidence suggesting the pharmacological potential of melatonergic compounds for treating pain. Importantly, MLT and melatonergic compounds seem to have a favorable toxicological profile than currently approved analgesic drugs. These compounds may thus deserve to be further developed as novel analgesic drugs, but this process relies on the use of appropriate and standardized experimental procedures. Therefore, in this chapter, we present the methodology to study the analgesic properties of MLT and melatonergic drugs in a preclinical model of chronic and acute pain. In addition to technical details of the surgical technique, details of anesthesia and perioperative care are also included.
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Affiliation(s)
- Danilo De Gregorio
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Comai
- Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
- Department of Biomedical Sciences, University of Padua, Padua, Italy.
- Department of Psychiatry, McGill University, Montreal, Canada.
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20
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Won E, Na KS, Kim YK. Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression. Int J Mol Sci 2021; 23:ijms23010305. [PMID: 35008730 PMCID: PMC8745430 DOI: 10.3390/ijms23010305] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/21/2021] [Accepted: 12/26/2021] [Indexed: 12/14/2022] Open
Abstract
Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.
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Affiliation(s)
- Eunsoo Won
- Department of Psychiatry, Chaum, Seoul 06062, Korea;
- Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea
| | - Kyoung-Sae Na
- Department of Psychiatry, Gachon University Gil Medical Center, Incheon 21565, Korea;
| | - Yong-Ku Kim
- Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Korea
- Correspondence:
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21
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Empowering Melatonin Therapeutics with Drosophila Models. Diseases 2021; 9:diseases9040067. [PMID: 34698120 PMCID: PMC8544433 DOI: 10.3390/diseases9040067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/14/2021] [Accepted: 09/22/2021] [Indexed: 12/15/2022] Open
Abstract
Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.
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22
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Ragothaman M, Kannan Villalan A, Dhanasekaran A, Palanisamy T. Bio-hybrid hydrogel comprising collagen-capped silver nanoparticles and melatonin for accelerated tissue regeneration in skin defects. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 128:112328. [PMID: 34474879 DOI: 10.1016/j.msec.2021.112328] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/29/2021] [Accepted: 07/18/2021] [Indexed: 01/22/2023]
Abstract
Hydrogel-based drug delivery systems have emerged as a promising platform for chronic tissue defects owing to their inherent ability to inhibit pathogenic infection and accelerate rapid tissue regeneration. Here, we fabricated a stable bio-hybrid hydrogel system comprising collagen, aminated xanthan gum, bio-capped silver nanoparticles and melatonin with antimicrobial, antioxidant and anti-inflammatory properties. Highly colloidal bio-capped silver nanoparticles were synthesized using collagen as a reducing cum stabilizing agent for the first time while aminated xanthan gum was synthesized using ethylenediamine treatment on xanthan gum. The synthesized bio-hybrid hydrogel exhibits better gelation, surface morphology, rheology and degelation properties. In vitro assessment of bio-hybrid hydrogel demonstrates excellent bactericidal efficiency against both common wound and multidrug-resistant pathogens and biocompatibility properties. In vivo animal studies demonstrate rapid tissue regeneration, collagen deposition and angiogenesis at the wound site predominantly due to the synergistic effect of silver nanoparticles and melatonin in the hydrogel. This study paves the way for developing biologically functional bio-nano hydrogel systems for promoting effective care for various ailments, including infected chronic wounds.
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Affiliation(s)
- Murali Ragothaman
- Centre for Biotechnology, Anna University, Chennai 600025, India; Advanced Materials Laboratory, Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020, India
| | - Arivizhivendhan Kannan Villalan
- Advanced Materials Laboratory, Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020, India
| | | | - Thanikaivelan Palanisamy
- Advanced Materials Laboratory, Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020, India.
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23
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Ramos E, López-Muñoz F, Gil-Martín E, Egea J, Álvarez-Merz I, Painuli S, Semwal P, Martins N, Hernández-Guijo JM, Romero A. The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy. Antioxidants (Basel) 2021; 10:1152. [PMID: 34356384 PMCID: PMC8301107 DOI: 10.3390/antiox10071152] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.
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Affiliation(s)
- Eva Ramos
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Francisco López-Muñoz
- Faculty of Health Sciences, University Camilo José Cela, C/Castillo de Alarcón 49, Villanueva de la Cañada, 28692 Madrid, Spain;
- Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute (i + 12), Avda. Córdoba, s/n, 28041 Madrid, Spain
- Portucalense Institute of Neuropsychology and Cognitive and Behavioural Neurosciences (INPP), Portucalense University, R. Dr. António Bernardino de Almeida 541, 4200-072 Porto, Portugal
- Thematic Network for Cooperative Health Research (RETICS), Addictive Disorders Network, Health Institute Carlos III, MICINN and FEDER, 28029 Madrid, Spain
| | - Emilio Gil-Martín
- Nutrition, Food & Plant Science Group NF1, Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, 36310 Vigo, Spain;
| | - Javier Egea
- Health Research Institute, Hospital Universitario de la Princesa, 28006 Madrid, Spain;
- Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28006 Madrid, Spain
| | - Iris Álvarez-Merz
- Department of Pharmacology and Therapeutic, Teófilo Hernando Institute, Faculty of Medicine, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029 Madrid, Spain; (I.Á.-M.); (J.M.H.-G.)
- Ramón y Cajal Institute for Health Research (IRYCIS), Hospital Ramón y Cajal, Carretera de Colmenar Viejo, Km. 9100, 28029 Madrid, Spain
| | - Sakshi Painuli
- Department of Biotechnology, Graphic Era University, Dehradun, Uttarakhand 248002, India; (S.P.); (P.S.)
| | - Prabhakar Semwal
- Department of Biotechnology, Graphic Era University, Dehradun, Uttarakhand 248002, India; (S.P.); (P.S.)
- Uttarakhand State Council for Science and Technology, Dehradun, Uttarakhand 248007, India
| | - Natália Martins
- Faculty of Medicine, Institute for Research and Innovation in Health (i3S), University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
- Institute for Research and Advanced Training in Health Sciences and Technologies, Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
| | - Jesús M. Hernández-Guijo
- Department of Pharmacology and Therapeutic, Teófilo Hernando Institute, Faculty of Medicine, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029 Madrid, Spain; (I.Á.-M.); (J.M.H.-G.)
- Ramón y Cajal Institute for Health Research (IRYCIS), Hospital Ramón y Cajal, Carretera de Colmenar Viejo, Km. 9100, 28029 Madrid, Spain
| | - Alejandro Romero
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;
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Kısadere İ, Aydın MF, Ündağ İ. Partial protective effects of melatonin on cadmium-induced changes in hematological characteristics in rats. Biotech Histochem 2021; 97:192-198. [PMID: 33998938 DOI: 10.1080/10520295.2021.1925965] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
We investigated the effects of melatonin (Mlt) on hematological characteristics to determine the percentage of alpha-naphthyl acetate esterase (ANAE) positive lymphocytes in rats chronically exposed to cadmium (Cd). We used four groups of male rats: control (C), melatonin (Mlt), cadmium (Cd) and Cd + Mlt (CdMlt). Blood samples were obtained to assess the erythrocytes (RBC), leukocytes (WBC), platelets (PLT), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) as well as alpha-naphthyl acetate esterase (ANAE) positive lymphocytes. We found that the number of WBC increased in the Cd group compared to the other three experimental groups. Low MCV and MCHC values caused by Cd were ameliorated by Mlt treatment in the CdMlt group. We found no significant change in the RBC, HGB, MCH, PLT and HCT values among the experimental groups. Mlt treatment also increased the percentage of ANAE positive lymphocytes. Mlt partially protects some hematological characteristics in cases of chronic Cd toxicity.
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Affiliation(s)
- İhsan Kısadere
- Department of Physiology, Faculty of Veterinary, University of Balıkesir, Balıkesir, Turkey
| | - Mehmet Faruk Aydın
- Department of Histology and Embryology, Faculty of Veterinary, University of Balıkesir, Balıkesir, Turkey
| | - İlknur Ündağ
- Department of Histology and Embryology, Faculty of Veterinary, University of Selcuk, Konya, Turkey
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Baudhuin H, Cousaert J, Vanwolleghem P, Raes G, Caveliers V, Keyaerts M, Lahoutte T, Xavier C. 68Ga-Labeling: Laying the Foundation for an Anti-Radiolytic Formulation for NOTA-sdAb PET Tracers. Pharmaceuticals (Basel) 2021; 14:ph14050448. [PMID: 34068666 PMCID: PMC8151064 DOI: 10.3390/ph14050448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/04/2021] [Accepted: 05/07/2021] [Indexed: 01/15/2023] Open
Abstract
During the preparation of [68Ga]Ga-NOTA-sdAb at high activity, degradation of the tracers was observed, impacting the radiochemical purity (RCP). Increasing starting activities in radiolabelings is often paired with increased degradation of the tracer due to the formation of free radical species, a process known as radiolysis. Radical scavengers and antioxidants can act as radioprotectant due to their fast interaction with formed radicals and can therefore reduce the degree of radiolysis. This study aims to optimize a formulation to prevent radiolysis during the labeling of NOTA derivatized single domain antibody (sdAbs) with 68Ga. Gentisic acid, ascorbic acid, ethanol and polyvinylpyrrolidone were tested individually or in combination to find an optimal mix able to prevent radiolysis without adversely influencing the radiochemical purity (RCP) or the functionality of the tracer. RCP and degree of radiolysis were assessed via thin layer chromatography and size exclusion chromatography for up to three hours after radiolabeling. Individually, the radioprotectants showed insufficient efficacy in reducing radiolysis when using high activities of 68Ga, while being limited in amount due to negative impact on radiolabeling of the tracer. A combination of 20% ethanol (VEtOH/VBuffer%) and 5 mg ascorbic acid proved successful in preventing radiolysis during labeling with starting activities up to 1-1.2 GBq of 68Ga, and is able to keep the tracer stable for up to at least 3 h after labeling at room temperature. The prevention of radiolysis by the combination of ethanol and ascorbic acid potentially allows radiolabeling compatibility of NOTA-sdAbs with all currently available 68Ge/68Ga generators. Additionally, a design is proposed to allow the incorporation of the radioprotectant in an ongoing diagnostic kit development for 68Ga labeling of NOTA-sdAbs.
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Affiliation(s)
- Henri Baudhuin
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
- Correspondence: ; Tel.: +32-2-477-4991
| | - Julie Cousaert
- Nuclear Medicine Department (NUCG), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, B-1090 Brussels, Belgium;
| | - Philippe Vanwolleghem
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
| | - Geert Raes
- Unit of Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium;
- Myeloid Cell Immunology Laboratory (MCI), VIB Center for Inflammation Research, Pleinlaan 2, B-1050 Brussels, Belgium
| | - Vicky Caveliers
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
- Nuclear Medicine Department (NUCG), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, B-1090 Brussels, Belgium;
| | - Marleen Keyaerts
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
- Nuclear Medicine Department (NUCG), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, B-1090 Brussels, Belgium;
| | - Tony Lahoutte
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
- Nuclear Medicine Department (NUCG), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, B-1090 Brussels, Belgium;
| | - Catarina Xavier
- Department of Medical Imaging (MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; (P.V.); (V.C.); (M.K.); (T.L.); (C.X.)
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Singh A, Dubey AK. Improved antibacterial and cellular response of electrets and piezobioceramics. J Biomater Appl 2021; 36:441-459. [PMID: 33599133 DOI: 10.1177/0885328221991965] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The bacterial contamination in implants has been recognized as one of the key issues in orthopedics. In this article, a new technique of electrical polarization of various non-piezoelectric and piezoelectric biocompatible ceramics has been explored to develop antibacterial implants. Optimally processed hydroxyapatite (HA), BaTiO3 (BT), CaTiO3 (CT), Na0.5K0.5NbO3 (NKN) and their composites have been used as model biomaterials to verify the concept. The phase evolution analyses and microstructural characterizations were performed for sintered samples. The samples were polarized at polarizing voltage and temperature of 20 kV and 500°C, respectively, for 30 min. The hydrophilicity of polarized surfaces was examined using deionized water and culture media. The polarization induced in-vitro antibacterial study was performed for both, gram positive and gram negative bacteria. The viability of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria reduces significantly on the polarized surfaces. In addition, the influence of polarization on antibacterial response has been explored via various mechanisms such as development of reactive oxygen species (ROS), catalase activity and lipoperoxidation. Furthermore, the cellular response of polarized surfaces was also examined using SaOS2 and MG-63 cells. The viability of SaOS2 and MG-63 cells was observed to increase significantly on negatively polarized surfaces. Overall, the surface treatment enhances the antibacterial response of HA, NKN, BT, CT and their composites surfaces with positive influence on cellular response.
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Affiliation(s)
- Angaraj Singh
- Department of Ceramic Engineering, Indian Institute of Technology (BHU), Varanasi, India
| | - Ashutosh Kumar Dubey
- Department of Ceramic Engineering, Indian Institute of Technology (BHU), Varanasi, India
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Yap CK, Wong KW, Al-Shami SA, Nulit R, Cheng WH, Aris AZ, Sharifinia M, Bakhtiari AR, Okamura H, Saleem M, Chew W, Ismail MS, Al-Mutairi KA. Human Health Risk Assessments of Trace Metals on the Clam Corbicula javanica in a Tropical River in Peninsular Malaysia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 18:ijerph18010195. [PMID: 33383875 PMCID: PMC7794960 DOI: 10.3390/ijerph18010195] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/23/2020] [Accepted: 12/24/2020] [Indexed: 12/21/2022]
Abstract
This study aimed to analyse ten trace metal concentrations in the edible part of the freshwater clam Corbicula javanica and to provide a critical assessment of the potential risks to human health through consumption of this clam as food based on well-established indices and food safety guidelines. The clams were captured from a pristine original site and transplanted to other sites with different environmental qualities. The trace metal levels in the edible total soft tissue (TST) of the clam were below those of the food safety guidelines referred to except for Pb, which exceeded the permissible limit set by the European Commission (2006) and the US Food and Drug Administration/ Center for Food Safety and Applied Nutrition); Interstate Shellfish Sanitation Conference. (USFDA/CFSAN; ISSC) (2007). The estimated daily intake (EDI) values of the clam were found to be lower than the oral reference dose and the calculated target hazard quotient (THQ) and total THQ were found to be less than 1. Therefore, in conclusion, the human health risk for consumption of TST of C. javanica at both average and high-level were insignificant regardless of the environment it was exposed to.
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Affiliation(s)
- Chee Kong Yap
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Selangor 43400, Malaysia; (K.W.W.); (R.N.)
- Correspondence: or
| | - Koe Wei Wong
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Selangor 43400, Malaysia; (K.W.W.); (R.N.)
| | - Salman Abdo Al-Shami
- Indian River Research and Education Center, IFAS, University of Florida, Fort Pierce, FL 34945, USA;
| | - Rosimah Nulit
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Selangor 43400, Malaysia; (K.W.W.); (R.N.)
| | - Wan Hee Cheng
- Faculty of Health and Life Sciences, Inti International University, Sembilan 71800, Malaysia;
| | - Ahmad Zaharin Aris
- Department of Environmental Sciences, Faculty of Environmental Studies, Universiti Putra Malaysia, Selangor 43400, Malaysia;
| | - Moslem Sharifinia
- Shrimp Research Center, Iranian Fisheries Science Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Bushehr 7516989177, Iran;
| | - Alireza Riyahi Bakhtiari
- Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Mazandaran 46417-76489, Iran;
| | - Hideo Okamura
- Faculty of Maritime Sciences, Graduate School of Maritime Sciences, Kobe University, Kobe 658-0022, Japan;
| | - Muhammad Saleem
- Department of Chemistry, Government Post Graduate College, Mirpur University of Science and Technology, Mirpur 10250, Pakistan;
| | - Weiyun Chew
- Centre for Pre-University Study, MAHSA University, Selangor 42610, Malaysia;
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Kose O, Kurt Bayrakdar S, Unver B, Altin A, Akyildiz K, Mercantepe T, Bostan SA, Arabaci T, Turker Sener L, Emre Kose T, Tumkaya L, Yilmaz A, Kuluslu G. Melatonin improves periodontitis-induced kidney damage by decreasing inflammatory stress and apoptosis in rats. J Periodontol 2020; 92:22-34. [PMID: 33251634 DOI: 10.1002/jper.20-0434] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/14/2020] [Accepted: 10/14/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin. METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1β, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine. RESULTS Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1β), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05). CONCLUSION Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.
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Affiliation(s)
- Oğuz Kose
- Department of Periodontology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey
| | - Sevda Kurt Bayrakdar
- Department of Periodontology, School of Dentistry, Eskişehir Osmangazi University, Eskisehir, Turkey
| | - Büsra Unver
- Department of Periodontology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey
| | - Ahmet Altin
- Department of Periodontology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey
| | - Kerimali Akyildiz
- Department of Medical Services and Techniques, School of Healh Care Services Vocational, Recep Tayyip Erdogan University, Rize, Turkey
| | - Tolga Mercantepe
- Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Semih Alperen Bostan
- Department of Periodontology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey
| | - Taner Arabaci
- Department of Periodontology, School of Dentistry, Ataturk University, Erzurum, Turkey
| | - Leyla Turker Sener
- Department of Biophysics School of Medicine, Istanbul University, Istanbul, Turkey
| | - Taha Emre Kose
- Department of Dentomaxillofacial Radiology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey
| | - Levent Tumkaya
- Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Adnan Yilmaz
- Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Göker Kuluslu
- 3D Medical and Industrial Design Laboratory, Istanbul University, Istanbul, Turkey
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Brazão V, Santello FH, Colato RP, Duarte A, Goulart A, Sampaio PA, Nardini V, Sorgi CA, Faccioli LH, do Prado JC. Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165914. [PMID: 32768678 PMCID: PMC7406476 DOI: 10.1016/j.bbadis.2020.165914] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 07/19/2020] [Accepted: 08/03/2020] [Indexed: 01/16/2023]
Abstract
Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and β (IL-1α and β), IL-6 and transforming growth factor beta (TGF-β) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 α and β concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-β. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.
Melatonin acts on the regulation of steroid hormones, apoptosis and cytokine signaling during acute T. cruzi infection; Middle-aged control rats have higher production of corticosterone, cortisone, cortisol and aldosterone; Melatonin treated middle-aged infected rats displayed reduced concentrations of IL-1 α and β; Melatonin levels were significantly higher in all middle-aged rats treated animals; Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats.
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Affiliation(s)
- Vânia Brazão
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
| | - Fabricia Helena Santello
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Rafaela Pravato Colato
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Andressa Duarte
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Amanda Goulart
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Pedro Alexandre Sampaio
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Viviani Nardini
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Carlos Arterio Sorgi
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Lúcia Helena Faccioli
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - José Clóvis do Prado
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
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Comai S, De Gregorio D, Posa L, Ochoa-Sanchez R, Bedini A, Gobbi G. Dysfunction of serotonergic activity and emotional responses across the light-dark cycle in mice lacking melatonin MT 2 receptors. J Pineal Res 2020; 69:e12653. [PMID: 32239546 DOI: 10.1111/jpi.12653] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 12/21/2022]
Abstract
Melatonin (MLT) levels fluctuate according to the external light/dark cycle in both diurnal and nocturnal mammals. We previously demonstrated that melatonin MT2 receptor knockout (MT2 -/- ) mice show a decreased nonrapid eye movement sleep over 24 hours and increased wakefulness during the inactive (light) phase. Here, we investigated the role of MT2 receptors in physiological light/dark cycle fluctuations in the activity of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons and anxiety- and depression-like behavior. We found that the 5-HT burst-firing activity was tonically reduced across the whole 24 hours in MT2 -/- mice compared with MT2 +/+ mice. Importantly, the physiological changes in the spontaneous firing activity of DRN 5-HT neurons during the light/dark cycle were nullified in MT2 -/- mice, with a higher DRN 5-HT neural firing activity during the light phase in MT2 -/- than in MT2 +/+ mice. The role of MT2 receptors over DRN 5-HT neurons was confirmed by acute pharmacological studies in which the selective MT2 receptors agonist UCM1014 dose dependently inhibited DRN 5-HT activity, mostly during the dark phase. Compared with MT2 +/+ , MT2 -/- mice displayed an anxiety-like phenotype in the novelty-suppressed feeding and in the light/dark box tests; while anxiety levels in the light/dark box test were lower during the dark than during the light phase in MT2 +/+ mice, the opposite was seen in MT2 -/- mice. No differences between MT2 +/+ and MT2 -/- mice were observed for depression-like behavior in the forced swim and in the sucrose preference tests. These results suggest that MT2 receptor genetic inactivation impacts 5-HT neurotransmission and interferes with anxiety levels by perturbing the physiologic light/dark pattern.
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Affiliation(s)
- Stefano Comai
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada
- Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy
| | - Danilo De Gregorio
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada
| | - Luca Posa
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada
| | - Rafael Ochoa-Sanchez
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada
| | - Annalida Bedini
- Department of Biomolecular Sciences, University Carlo Bo, Urbino, Italy
| | - Gabriella Gobbi
- Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada
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Gurunathan S, Kang MH, Kim JH. Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers. Cancers (Basel) 2020; 12:cancers12061567. [PMID: 32545820 PMCID: PMC7352348 DOI: 10.3390/cancers12061567] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 06/04/2020] [Accepted: 06/11/2020] [Indexed: 02/06/2023] Open
Abstract
Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.
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Bulbul F, Koca I, Savas E, Dokuyucu R. The Comparison of the Biological Rhythms of Patients with Fibromyalgia Syndrome with Biological Rhythms of Healthy Controls. Med Sci Monit 2020; 26:e920462. [PMID: 32094321 PMCID: PMC7059434 DOI: 10.12659/msm.920462] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Background Fibromyalgia syndrome (FMS) is a rheumatic disease characterized by diffuse body pain and decreased muscle function. The aim of the present study was to compare the biological rhythms of patients with fibromyalgia syndrome with the biological rhythms of healthy controls. Material/Methods This was a cross-sectional, single blind, and single center case-control study. The patients with fibromyalgia were evaluated using a Fibromyalgia Impact Questionnaire (FIQ), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) Scale, Visual Analog Scale (VAS), Pittsburg Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI). Results The study included 77 female patients with FMS, and 32 healthy female individuals as the control group. We found that the patients in the FMS group achieved higher scores in VAS, BDI, PSQI, and the BRIAN scale than the patients in the control group (P<0.001). An evaluation of the relationship between FMS evaluation parameters and biological rhythm scores in patients with FMS revealed a significant positive correlation between total BRAIN and VAS, FIQ, BDI, and PSQI scores. When the relationship between FMS evaluation parameters and biological rhythm scores was evaluated in patients with FMS, a significant positive correlation was found between total BRAIN and VAS, FIQ, BDI, and PSQI scores (r=0.555, P<0.001; r=0.461, P<0.001; r=0.630, P<0.001; and r=0.551, P<0.001 respectively). Conclusions We consider that an evaluation of the biological rhythm of female patients with FMS, and appropriate treatment when required, would contribute significantly to the treatment and follow-up process of the patients.
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Affiliation(s)
- Feridun Bulbul
- Department of Psychiatry, School of Medicine, Cukurova University, Adana, Turkey
| | - Irfan Koca
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Esen Savas
- Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Recep Dokuyucu
- Department of Physiology, Medical Specialty Training Center (TUSMER), Ankara, Turkey
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Olanrewaju H, Miller W, Maslin W, Collier S, Purswell J, Branton S. Interactive effects of light-sources, photoperiod, and strains on growth performance, carcass characteristics, and health indices of broilers grown to heavy weights1. Poult Sci 2019; 98:6232-6240. [PMID: 31420665 PMCID: PMC8913770 DOI: 10.3382/ps/pez476] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/30/2019] [Indexed: 11/20/2022] Open
Abstract
Effects of light sources, photoperiods, and strains on growth performance, carcass characteristics, and health indices of broilers grown to heavy weights (>3 kg) were evaluated. The experimental design was a 4 × 2 × 2 factorial treatments consisting of 4 light sources [incandescent (ICD, standard), compact fluorescent light, neutral light emitting diode (Neutral-LED), and cool poultry specific LED (Cool-poultry specific (PS)-LED)], 2 photoperiods (regular/intermittent [2L:2D], and short [8L:16D]), and 2 strains (A, B). In each trial, chicks of 2 different strains from different commercial hatcheries were equally and randomly distributed into 16 environmentally controlled rooms at 1 D of age. Each room was randomly assigned one of 16 treatments from day 1 to 56 D of age. Feed and water were provided ad libitum. Birds were provided a 4 phase-feeding program (starter, grower, finisher, withdrawal). Birds and feed were weighed on 1, 14, 28, 42, and 56 D of age for growth performance. On day 56, a total of 20 (10 males and 10 females) birds from each room were processed to determine weights and yields. The BW, BW gain, live weight, and carcass weight of birds reared under PS-LED were higher (P < 0.05) in comparison with birds reared under ICD, but feed intake, feed conversion ratio, mortality, and carcass characteristics were not affected by treatments. Also, broilers subjected to the short/non-intermittent photoperiod had the lowest (P < 0.05) growth performance and carcass characteristics compared with values obtained for regular/intermittent photoperiods. In addition, strain was significant (P < 0.05) for most of the examined variables. Feed conversion, fat, tender, and yield were not affected by treatments. There was no effect of photoperiod, light sources, or their interactions on mortality. This study shows positive impacts on alternative light sources when compared to ICD along with regular/intermittent photoperiod in commercial poultry facilities rearing the 2 strains used in this study, thereby reducing energy costs and optimizing production efficiency without compromising the welfare of broilers grown to heavy weights.
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Affiliation(s)
- H.A. Olanrewaju
- USDA, Agricultural Research Service, Poultry Research Unit, Mississippi State University, Starkville, MS 39762-5367
| | - W.W. Miller
- Advanced Animal Eye Care, Starkville, MS 39759
| | - W.R. Maslin
- College of Veterinary Medicine, Wise Center, Mississippi State University, Starkville, MS 39762
| | - S.D. Collier
- USDA, Agricultural Research Service, Poultry Research Unit, Mississippi State University, Starkville, MS 39762-5367
| | - J.L. Purswell
- USDA, Agricultural Research Service, Poultry Research Unit, Mississippi State University, Starkville, MS 39762-5367
| | - S.L. Branton
- USDA, Agricultural Research Service, Poultry Research Unit, Mississippi State University, Starkville, MS 39762-5367
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Zhu H, Chen Y, Bai LC, Cao XR, Xu R. Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner. Dose Response 2019; 17:1559325819877271. [PMID: 31579126 PMCID: PMC6759722 DOI: 10.1177/1559325819877271] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 08/18/2018] [Accepted: 08/20/2019] [Indexed: 11/17/2022] Open
Abstract
The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was measured by MTT assay at various concentrations. Ten micrometer melatonin promoted the cell-killing effects of IR, while 1000-µM melatonin prevented IR-induced cellular inactivation. Further analysis revealed that 1000-µM melatonin protected the cells from IR-induced reactive oxygen species damage, as the oxidative stress measured by fluorescent microscopy and fluorescence-activated cell sorting using 2,7-dichlorofluorescein diacetate staining. This is further confirmed by melatonin receptor agonist, which has no antioxidant capacity. A 10-µM melatonin, on the contrary, enhanced the cell-killing effects of IR by activating c-Jun NH2-terminal kinase (JNK) signaling. c-Jun NH2-terminal kinase signaling activation was indicated by Western blot of phosphorylated JNK. We used JNK inhibitor to further confirm the involvement of JNK signaling in the cell-killing enhancement of 10-µM melatonin administration. Our results suggest the importance of dose-dependent effects in melatonin application for radiotherapy.
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Affiliation(s)
- Hao Zhu
- Radiology Department, Lanzhou University Second Hospital, Lanzhou, China
| | - Yong Chen
- MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Liang-Cai Bai
- Radiology Department, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiang-Rong Cao
- Radiology Department, Lanzhou University Second Hospital, Lanzhou, China
| | - Rui Xu
- Radiology Department, Lanzhou University Second Hospital, Lanzhou, China
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Tchekalarova J, Angelova VT, Todorova N, Andreeva-Gateva P, Rangelov M. Evaluation of the anticonvulsant effect of novel melatonin derivatives in the intravenous pentylenetetrazol seizure test in mice. Eur J Pharmacol 2019; 863:172684. [PMID: 31545983 DOI: 10.1016/j.ejphar.2019.172684] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/06/2019] [Accepted: 09/19/2019] [Indexed: 02/06/2023]
Abstract
The design of new pharmacologically active compounds with affinity to melatonin receptors has become an area of great interest during the last decade. Recently, we reported that newly synthesized melatonin derivatives, containing aroylhydrazone moiety in the indole scaffold, with the highest affinity to the elaborated pharmacophore model, possess an anticonvulsant activity in the maximal electroshock (MES) and 6Hz test in mice. We aimed further to explore the effect of these melatonin derivatives and the role of melatonin receptors on seizure threshold measured by the timed intravenous pentylenetetrazole (iv PTZ) infusion test in mice. Carbamazepine (CBZ) and melatonin were used as positive controls. Three out of six compounds, 3c, 3f, and 3e, respectively, dose-dependently increased the PTZ-induced seizure thresholds for myoclonic twitch, clonic, and tonic seizures comparable to the effect of CBZ and melatonin. The anticonvulsant effect of 3c, 3f, and 3e was blocked by the non-selective melatonin receptor antagonist luzindol suggesting the involvement of melatonin receptors in the activity of these compounds. Also docking study of 3c, 3f and 3e in the melatonin-binding site of melatonin receptor confirm the possible mechanism of action of these compounds involving melatonin receptors. Our previous and present results suggest that 3c, 3f, and 3e can be considered promising agents with anticonvulsant activity on melatonin receptors in the brain.
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Affiliation(s)
- Jana Tchekalarova
- Institute of Neurobiology, Bulgarian Academy of Sciences (BAS), Bulgaria.
| | | | | | | | - Miroslav Rangelov
- Institute of Organic Chemistry with a Center of Phytochemistry, BAS, Bulgaria
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Oleshchuk O, Ivankiv Y, Falfushynska H, Mudra A, Lisnychuk N. Hepatoprotective Effect of Melatonin in Toxic Liver Injury in Rats. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E304. [PMID: 31238587 PMCID: PMC6631928 DOI: 10.3390/medicina55060304] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 06/17/2019] [Accepted: 06/18/2019] [Indexed: 02/07/2023]
Abstract
Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group) or the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but concentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were less severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl4-induced hepatitis.
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Affiliation(s)
- Oleksandra Oleshchuk
- Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil State Medical University, Maidan Voli sq. 1, 46001 Ternopil, Ukraine.
| | - Yana Ivankiv
- Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil State Medical University, Maidan Voli sq. 1, 46001 Ternopil, Ukraine.
| | - Halina Falfushynska
- Department of orthopedagogy and physical therapy, Ternopil V. Hnatiuk National Pedagogical University, Maxym Kryvonis str. 2, 46027 Ternopil, Ukraine.
| | - Alla Mudra
- Department of Medical Biochemistry, I. Horbachevsky Ternopil State Medical University, Maidan Voli sq 1., 46001 Ternopil, Ukraine.
| | - Nataliya Lisnychuk
- Central Scientific Research Laboratory, I. Horbachevsky Ternopil State Medical University, Maidan Voli sq. 1, 46001 Ternopil, Ukraine.
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Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives. Pharmacol Res 2019; 144:343-356. [DOI: 10.1016/j.phrs.2019.04.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 03/06/2019] [Accepted: 04/11/2019] [Indexed: 12/15/2022]
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Gupta J, Fatima MT, Islam Z, Khan RH, Uversky VN, Salahuddin P. Nanoparticle formulations in the diagnosis and therapy of Alzheimer's disease. Int J Biol Macromol 2019; 130:515-526. [DOI: 10.1016/j.ijbiomac.2019.02.156] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 02/27/2019] [Accepted: 02/27/2019] [Indexed: 12/11/2022]
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Li Y, Cui X, Li Z, Jia Q, Jiang L, Zhang Z, Lu Q, Wang J, Jiang L. High melatonin levels are related to spinal ossification in patients with ankylosing spondylitis. Mod Rheumatol 2019; 30:373-378. [PMID: 30922195 DOI: 10.1080/14397595.2019.1601854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Objectives: To investigate associations of serum melatonin with spinal ossification and cytokines in ankylosing spondylitis (AS).Methods: Serum was obtained from 52 AS patients and 25 healthy controls. Melatonin was measured by ELISA kit; bone morphogenetic protein (BMP)-2, dickkopf-related protein (Dkk)-1, IL-1β, IL-6, IL-17 and TNF-α concentrations were assayed using Luminex multiplex bead system. Osteocalcin and β isomer of C-terminal telopeptide of type I collagen (β-CTX) were measured using electrochemiluminescence immunoassay. Spinal damages were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) on radiographs.Results: Serum melatonin was significantly increased in AS patients. Serum melatonin correlated positively with mSASSS after multivariate adjustment for age and disease duration (r = 0.70, p < .01). Patients with spinal bone bridge have higher levels of melatonin than those without spinal bone bridge [16.69 (4.65, 41.10) pg/ml vs. 7.43 (3.29, 15.30) pg/ml, p = .03]. The multiple linear regression analysis found that melatonin was a risk factor for spinal bone formation (β = 0.35, p < .05). Additionally, melatonin correlated positively with osteocalcin (r = 0.34, p = .04) and IL-1β (r = 0.39, p = .04) in AS.Conclusion: Melatonin is increased in AS patients, especially in patients with spinal bone bridge. It suggests that melatonin may play an important role in the pathological osteogenesis of AS.
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Affiliation(s)
- Yanshan Li
- Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.,Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Xiaomeng Cui
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zunzhong Li
- Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Qian Jia
- Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Li Jiang
- Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Zhenchun Zhang
- Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Qing Lu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jibo Wang
- Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Lindi Jiang
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
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Gil-Martín E, Egea J, Reiter RJ, Romero A. The emergence of melatonin in oncology: Focus on colorectal cancer. Med Res Rev 2019; 39:2239-2285. [PMID: 30950095 DOI: 10.1002/med.21582] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/04/2019] [Accepted: 03/16/2019] [Indexed: 12/17/2022]
Abstract
Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti-CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.
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Affiliation(s)
- Emilio Gil-Martín
- Department of Biochemistry, Genetics and Immunology, Biomedical Research Center (CINBIO, 'Centro Singular de Investigación de Galicia'), University of Vigo, Vigo, Spain
| | - Javier Egea
- Molecular Neuroinflammation and Neuronal Plasticity Laboratory, Research Unit, Hospital Universitario Santa Cristina, Madrid, Spain.,Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Madrid, Spain.,Departamento de Farmacología y Terapéutica, Instituto-Fundación Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain
| | - Russel J Reiter
- Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, Texas, USA
| | - Alejandro Romero
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
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Genario R, Giacomini AC, Demin KA, dos Santos BE, Marchiori NI, Volgin AD, Bashirzade A, Amstislavskaya TG, de Abreu MS, Kalueff AV. The evolutionarily conserved role of melatonin in CNS disorders and behavioral regulation: Translational lessons from zebrafish. Neurosci Biobehav Rev 2019; 99:117-127. [DOI: 10.1016/j.neubiorev.2018.12.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 12/12/2018] [Accepted: 12/20/2018] [Indexed: 12/14/2022]
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Scarpelli PH, Tessarin‐Almeida G, Viçoso KL, Lima WR, Borges‐Pereira L, Meissner KA, Wrenger C, Rafaello A, Rizzuto R, Pozzan T, Garcia CRS. Melatonin activates FIS1, DYN1, and DYN2 Plasmodium falciparum related-genes for mitochondria fission: Mitoemerald-GFP as a tool to visualize mitochondria structure. J Pineal Res 2019; 66:e12484. [PMID: 29480948 PMCID: PMC6585791 DOI: 10.1111/jpi.12484] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 02/01/2018] [Indexed: 02/06/2023]
Abstract
Malaria causes millions of deaths worldwide and is considered a huge burden to underdeveloped countries. The number of cases with resistance to all antimalarials is continuously increasing, making the identification of novel drugs a very urgent necessity. A potentially very interesting target for novel therapeutic intervention is the parasite mitochondrion. In this work, we studied in Plasmodium falciparum 3 genes coding for proteins homologues of the mammalian FIS1 (Mitochondrial Fission Protein 1) and DRP1 (Dynamin Related Protein 1) involved in mitochondrial fission. We studied the expression of P. falciparum genes that show ample sequence and structural homologies with the mammalian counterparts, namely FIS1, DYN1, and DYN2. The encoded proteins are characterized by a distinct pattern of expression throughout the erythrocytic cycle of P. falciparum, and their mRNAs are modulated by treating the parasite with the host hormone melatonin. We have previously reported that the knockout of the Plasmodium gene that codes for protein kinase 7 is essential for melatonin sensing. We here show that PfPk7 knockout results in major alterations of mitochondrial fission genes expression when compared to wild-type parasites, and no change in fission proteins expression upon treatment with the host hormone. Finally, we have compared the morphological characteristics (using MitoTracker Red CMX Ros) and oxygen consumption properties of P. falciparum mitochondria in wild-type parasites and PfPk7 Knockout strains. A novel GFP construct targeted to the mitochondrial matrix to wild-type parasites was also developed to visualize P. falciparum mitochondria. We here show that, the functional characteristics of P. falciparum are profoundly altered in cells lacking protein kinase 7, suggesting that this enzyme plays a major role in the control of mitochondrial morphogenesis and maturation during the intra-erythrocyte cell cycle progression.
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Affiliation(s)
- Pedro H. Scarpelli
- Departamento de ParasitologiaInstituto de Ciências BiomédicasUniversidade de São PauloSão PauloBrazil
- Departamento de FisiologiaInstituto de BiociênciasUniversidade de São PauloSão PauloBrazil
| | | | - Kênia Lopes Viçoso
- Departamento de FisiologiaInstituto de BiociênciasUniversidade de São PauloSão PauloBrazil
| | - Wania Rezende Lima
- Instituto de Ciências Exatas e Naturais‐MedicinaUniversidade Federal de Mato Grosso‐Campus RondonópolisMato GrossoBrazil
| | - Lucas Borges‐Pereira
- Departamento de FisiologiaInstituto de BiociênciasUniversidade de São PauloSão PauloBrazil
| | - Kamila Anna Meissner
- Departamento de ParasitologiaInstituto de Ciências BiomédicasUniversidade de São PauloSão PauloBrazil
| | - Carsten Wrenger
- Departamento de ParasitologiaInstituto de Ciências BiomédicasUniversidade de São PauloSão PauloBrazil
| | - Anna Rafaello
- CNR Neurosciences InstituteUniversity of PadovaPadovaItaly
| | | | - Tullio Pozzan
- CNR Neurosciences InstituteUniversity of PadovaPadovaItaly
| | - Celia R. S. Garcia
- Departamento de FisiologiaInstituto de BiociênciasUniversidade de São PauloSão PauloBrazil
- Departamento de Fisiologia, Instituto de BiociênciasUniversidade de São PauloSão PauloBrazil
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Castaño MY, Garrido M, Rodríguez AB, Gómez MÁ. Melatonin Improves Mood Status and Quality of Life and Decreases Cortisol Levels in Fibromyalgia. Biol Res Nurs 2018; 21:22-29. [DOI: 10.1177/1099800418811634] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Background: Mood disturbances are implicated in the pathogenesis of fibromyalgia. The aim of this study was to assess the effect of different doses of melatonin on quality of life, mood status, pain, anxiety, and urinary cortisol levels in patients with fibromyalgia. Methods: After a 10-day baseline period for the collection of data about participants’ initial status, participants took different doses of melatonin for 10 consecutive days each, with placebo given during the 10 days either before or between melatonin doses. Participants’ moods, quality of life, and pain levels were assessed using the Fibromyalgia Impact Questionnaire (FIQ), a Numerical Pain Scale (NPS), the State-Trait Anxiety Test (STAI), a Visual Analog Scale (VAS), and the Short Form-36 Health Survey (SF-36). Urinary cortisol levels were measured using enzyme-linked immunoassay. Results: Doses of 9, 12, and 15 mg of melatonin were associated with decreases in the total score of the FIQ, NPS scores, and urinary cortisol levels. The State-Anxiety subscale of the STAI improved after the 12 mg dose. The scores on the VAS improved after the 9 mg dose. The dimensions evaluated in the SF-36 questionnaire improved after the 9 mg dose. Conclusion: Melatonin improved mood, anxiety levels, and quality of life while decreasing cortisol levels in patients with fibromyalgia.
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Affiliation(s)
- M. Yolanda Castaño
- Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain
| | - Maria Garrido
- Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain
| | - Ana Beatriz Rodríguez
- Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain
| | - M. Ángeles Gómez
- Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain
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Kanwar MK, Yu J, Zhou J. Phytomelatonin: Recent advances and future prospects. J Pineal Res 2018; 65:e12526. [PMID: 30256447 DOI: 10.1111/jpi.12526] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 09/16/2018] [Accepted: 09/18/2018] [Indexed: 12/13/2022]
Abstract
Melatonin (MEL) has been revealed as a phylogenetically conserved molecule with a ubiquitous distribution from primitive photosynthetic bacteria to higher plants, including algae and fungi. Since MEL is implicated in numerous plant developmental processes and stress responses, the exploration of its functions in plant has become a rapidly progressing field with the new paradigm of involvement in plants growth and development. The pleiotropic involvement of MEL in regulating the transcripts of numerous genes confirms its vital involvement as a multi-regulatory molecule that architects many aspects of plant development. However, the cumulative research in plants is still preliminary and fragmentary in terms of its established functions compared to what is known about MEL physiology in animals. This supports the need for a comprehensive review that summarizes the new aspects pertaining to its functional role in photosynthesis, phytohormonal interactions under stress, cellular redox signaling, along with other regulatory roles in plant immunity, phytoremediation, and plant microbial interactions. The present review covers the latest advances on the mechanistic roles of phytomelatonin. While phytomelatonin is a sovereign plant growth regulator that can interact with the functions of other plant growth regulators or hormones, its qualifications as a complete phytohormone are still to be established. This review also showcases the yet to be identified potentials of phytomelatonin that will surely encourage the plant scientists to uncover new functional aspects of phytomelatonin in plant growth and development, subsequently improving its status as a potential new phytohormone.
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Affiliation(s)
- Mukesh Kumar Kanwar
- Department of Horticulture, Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zijingang Campus, Zhejiang University, Hangzhou, China
| | - Jingquan Yu
- Department of Horticulture, Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zijingang Campus, Zhejiang University, Hangzhou, China
- Key Laboratory of Horticultural Plants Growth, Development and Quality Improvement, Agricultural Ministry of China, Hangzhou, China
| | - Jie Zhou
- Department of Horticulture, Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zijingang Campus, Zhejiang University, Hangzhou, China
- Key Laboratory of Horticultural Plants Growth, Development and Quality Improvement, Agricultural Ministry of China, Hangzhou, China
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Drzeżdżon J, Jacewicz D, Chmurzyński L. The impact of environmental contamination on the generation of reactive oxygen and nitrogen species - Consequences for plants and humans. ENVIRONMENT INTERNATIONAL 2018; 119:133-151. [PMID: 29957355 DOI: 10.1016/j.envint.2018.06.019] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 06/15/2018] [Accepted: 06/16/2018] [Indexed: 05/23/2023]
Abstract
Environmental contaminants, such as heavy metals, nanomaterials, and pesticides, induce the formation of reactive oxygen and nitrogen species (RONS). Plants interact closely with the atmosphere, water, and soil, and consequently RONS intensely affect their biochemistry. For the past 30 years researchers have thoroughly examined the role of RONS in plant organisms and oxidative modifications to cellular components. Hydrogen peroxide, superoxide anion, nitrogen(II) oxide, and hydroxyl radicals have been found to take part in many metabolic pathways. In this review the various aspects of the oxidative stress induced by environmental contamination are described based on an analysis of literature. The review reinforces the contention that RONS play a dual role, that is, both a deleterious and a beneficial one, in plants. Environmental contamination affects human health, also, and so we have additionally described the impact of RONS on the coupled human - environment system.
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Affiliation(s)
- Joanna Drzeżdżon
- Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland
| | - Dagmara Jacewicz
- Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
| | - Lech Chmurzyński
- Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland
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Brazão V, Colato RP, Santello FH, Vale GTD, Gonzaga NDA, Tirapelli CR, Prado JCD. Effects of melatonin on thymic and oxidative stress dysfunctions during Trypanosoma cruzi infection. J Pineal Res 2018; 65:e12510. [PMID: 29781553 DOI: 10.1111/jpi.12510] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 04/09/2018] [Indexed: 12/11/2022]
Abstract
Although the exact etiology of Chagas disease is not completely elucidated, thymic atrophy and oxidative stress are believed to be important contributors to the pathogenesis during acute Trypanosoma cruzi (T. cruzi) infection. We hypothesized that exogenous melatonin, administered by gavage (5 mg/kg, p.o., gavage) to young (5 weeks old) and middle-aged (18 months old) male Wistar rats, would modulate thymic oxidative damage and reverse the age-related thymus regression during T. cruzi acute infection. Increased levels of superoxide anion (O2- ) were detected in the thymus of infected animals, and treatment with melatonin reverted this response. We found reduced TBARS levels as well as a significant increase in superoxide dismutase (SOD) activity in the thymus of all middle-aged melatonin-treated animals, infected or not with T. cruzi. Furthermore, melatonin increased the thymic expression of SOD1 and SOD2 in middle-aged control animals. Nox2 expression was not affected by melatonin treatment in young or middle-aged animals. Melatonin reverted the age-related thymic regression as revealed by the increase in thymus weight, total number of thymocytes, and reduction in age-related accumulation of double-negative thymocytes. This is the first report to directly examine the effects of melatonin treatment on the thymic antioxidant/oxidant status and thymic changes during T. cruzi infection. Our results revealed new antioxidant features that turn melatonin a potentially useful compound for the treatment of Chagas disease, a condition in which an excessive oxidative damage occurs.
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Affiliation(s)
- Vânia Brazão
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Rafaela Pravato Colato
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Fabricia Helena Santello
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Gabriel Tavares do Vale
- Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil
| | - Natália de Almeida Gonzaga
- Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil
| | - Carlos Renato Tirapelli
- Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil
| | - José Clóvis do Prado
- College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil
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Zhao X, Wang D, Wu Z, Pan B, Yang H, Zeng C, Zhang M, Liu G, Han H, Zhou G. Female Reproductive Performance in the Mouse: Effect of Oral Melatonin. Molecules 2018; 23:molecules23081845. [PMID: 30044372 PMCID: PMC6222631 DOI: 10.3390/molecules23081845] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/20/2018] [Accepted: 07/23/2018] [Indexed: 12/20/2022] Open
Abstract
Although melatonin has some of the broadest ranges of actions on the physiology of vertebrates, especially on their reproductive processes, the mechanism by which melatonin regulates animal reproduction is still incompletely understood. This study was designed to determine the effect of oral melatonin on the reproductive performance of female mice. Female ICR mice (7 weeks old) were given melatonin-containing water (3, 30 and 300 μg/mL; melatonin) or water only (control) until 10 weeks of age. Then, some of the mice were successfully mated (confirmed by vaginal plugs), and the number of live births and their weights were recorded. Some mice were used for a histological analysis of the number of follicles in the ovaries. Others were used for oocyte collection after superovulation, and in vitro fertilization (IVF) was performed. The mRNA expression of the apopotosis-related genes (BAX, BCL2) in the IVF embryos were analyzed. After melatonin administration, the mice showed similar serum melatonin levels to that of the control. The number of antral follicles per mm² unit area in the 30 μg/mL melatonin-treated group (14.60) was significantly higher than that of the control (7.78), which was lower than that of the 3 μg/mL melatonin-treated group (12.29). The litter size was significantly higher in the 3 μg/mL melatonin-treated group (15.5) than in the control (14.3). After IVF, the hatched blastocyst formation rate in the 30 μg/mL melatonin-treated group (85.70%) was significantly higher than that of the control (72.10%), and it was the same for the BCL2/BAX expression ratio. Although oral melatonin did not appear to have an effect on the serum melatonin rhythm in the mouse, melatonin did increase litter size at the 3 μg/mL dose level, and improved the developmental competency of IVF embryos at the 30 μg/mL level.
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Affiliation(s)
- Xiaoxue Zhao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Dian Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Zhenzheng Wu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Bo Pan
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Haoxuan Yang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Changjun Zeng
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Ming Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
| | - Guoshi Liu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
| | - Hongbing Han
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
| | - Guangbin Zhou
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
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Onaolapo OJ, Onaolapo AY. Melatonin in drug addiction and addiction management: Exploring an evolving multidimensional relationship. World J Psychiatry 2018; 8:64-74. [PMID: 29988891 PMCID: PMC6033744 DOI: 10.5498/wjp.v8.i2.64] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 05/06/2018] [Accepted: 05/10/2018] [Indexed: 02/05/2023] Open
Abstract
Melatonin is a pleiotropic signalling molecule that regulates several physiological functions, and synchronises biological rhythms. Recent evidences are beginning to reveal that a dysregulation of endogenous melatonin rhythm or action may play a larger role in the aetiology and behavioural expression of drug addiction, than was previously considered. Also, the findings from a number of animal studies suggest that exogenous melatonin supplementation and therapeutic manipulation of melatonin/melatonin receptor interactions may be beneficial in the management of behavioural manifestations of drug addiction. However, repeated exogenous melatonin administration may cause a disruption of its endogenous rhythm and be associated with potential drawbacks that might limit its usefulness. In this review, we examine the roles of melatonin and its receptors in addictive behaviours; discussing how our understanding of melatonin’s modulatory effects on the brain rewards system and crucial neurotransmitters such as dopamine has evolved over the years. Possible indications(s) for melatonergic agents in addiction management, and how manipulations of the endogenous melatonin system may be of benefit are also discussed. Finally, the potential impediments to application of melatonin in the management of addictive behaviours are considered.
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Affiliation(s)
- Olakunle J Onaolapo
- Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Osogbo 230263, Osun State, Nigeria
| | - Adejoke Y Onaolapo
- Behavioural Neuroscience/Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho 210211, Oyo State, Nigeria
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Lewis SR, Pritchard MW, Schofield‐Robinson OJ, Alderson P, Smith AF, Cochrane Emergency and Critical Care Group. Melatonin for the promotion of sleep in adults in the intensive care unit. Cochrane Database Syst Rev 2018; 5:CD012455. [PMID: 29746721 PMCID: PMC6353085 DOI: 10.1002/14651858.cd012455.pub2] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and patients perceive the quality of their sleep to be poor whilst in the ICU. Artificial lighting during night-time hours in the ICU may contribute to reduced production of melatonin in critically ill patients. Melatonin is known to have a direct effect on the circadian rhythm, and it appears to reset a natural rhythm, thus promoting sleep. OBJECTIVES To assess whether the quantity and quality of sleep may be improved by administration of melatonin to adults in the intensive care unit. To assess whether melatonin given for sleep promotion improves both physical and psychological patient outcomes. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE (1946 to September 2017), Embase (1974 to September 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to September 2017), and PsycINFO (1806 to September 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA We included randomized and quasi-randomized controlled trials with adult participants (over the age of 16) admitted to the ICU with any diagnoses given melatonin versus a comparator to promote overnight sleep. We included participants who were mechanically ventilated and those who were not mechanically ventilated. We planned to include studies that compared the use of melatonin, given at an appropriate clinical dose with the intention of promoting night-time sleep, against no agent; or against another agent administered specifically to promote sleep. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings. We assessed the quality of evidence with GRADE. MAIN RESULTS We included four studies with 151 randomized participants. Two studies included participants who were mechanically ventilated, one study included a mix of ventilated and non-ventilated participants and in one study participants were being weaned from mechanical ventilation. Three studies reported admission diagnoses, which varied: these included sepsis, pneumonia and cardiac or cardiorespiratory arrest. All studies compared melatonin against no agent; three were placebo-controlled trials; and one compared melatonin with usual care. All studies administered melatonin in the evening.All studies reported adequate methods for randomization and placebo-controlled trials were blinded at the participant and personnel level. We noted high risk of attrition bias in one study and were unclear about potential bias introduced in two studies with differences between participants at baseline.It was not appropriate to combine data owing to differences in measurement tools, or methods used to report data.The effects of melatonin on subjectively rated quantity and quality of sleep are uncertain (very low certainty evidence). Three studies (139 participants) reported quantity and quality of sleep as measured through reports of participants or family members or by personnel assessments. Study authors in one study reported no difference in sleep efficiency index scores between groups for participant assessment (using Richards-Campbell Sleep Questionnaire) and nurse assessment. Two studies reported no difference in duration of sleep observed by nurses.The effects of melatonin on objectively measured quantity and quality of sleep are uncertain (very low certainty evidence). Two studies (37 participants) reported quantity and quality of sleep as measured by polysomnography (PSG), actigraphy, bispectral index (BIS) or electroencephalogram (EEG). Study authors in one study reported no difference in sleep efficiency index scores between groups using BIS and actigraphy. These authors also reported longer sleep in participants given melatonin which was not statistically significant, and improved sleep (described as "better sleep") in participants given melatonin from analysis of area under the curve (AUC) of BIS data. One study used PSG but authors were unable to report data because of a large loss of participant data.One study (82 participants) reported no evidence of a difference in anxiety scores (very low certainty evidence). Two studies (94 participants) reported data for mortality: one study reported that overall one-third of participants died; and one study reported no evidence of difference between groups in hospital mortality (very low certainty). One study (82 participants) reported no evidence of a difference in length of ICU stay (very low certainty evidence). Effects of melatonin on adverse events were reported in two studies (107 participants), and are uncertain (very low certainty evidence): one study reported headache in one participant given melatonin, and one study reported excessive sleepiness in one participant given melatonin and two events in the control group (skin reaction in one participant, and excessive sleepiness in another participant).The certainty of the evidence for each outcome was limited by sparse data with few participants. We noted study limitations in some studies due to high attrition and differences between groups in baseline data; and doses of melatonin varied between studies. Methods used to measure data were not consistent for outcomes, and use of some measurement tools may not be effective for use on the ICU patient. All studies included participants in the ICU but we noted differences in ICU protocols, and one included study used a non-standard sedation protocol with participants which introduced indirectness to the evidence. AUTHORS' CONCLUSIONS We found insufficient evidence to determine whether administration of melatonin would improve the quality and quantity of sleep in ICU patients. We identified sparse data, and noted differences in study methodology, in ICU sedation protocols, and in methods used to measure and report sleep. We identified five ongoing studies from database and clinical trial register searches. Inclusion of data from these studies in future review updates would provide more certainty for the review outcomes.
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Affiliation(s)
- Sharon R Lewis
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Michael W Pritchard
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Oliver J Schofield‐Robinson
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Phil Alderson
- National Institute for Health and Care ExcellenceLevel 1A, City Tower,Piccadilly PlazaManchesterUKM1 4BD
| | - Andrew F Smith
- Royal Lancaster InfirmaryDepartment of AnaesthesiaAshton RoadLancasterLancashireUKLA1 4RP
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