PMID: 

J Ren Nutr. 2019 Oct 6. Epub 2019 Oct 6. PMID: 31597622

Abstract Title: 

The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract: 

OBJECTIVE: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients.DESIGN: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI.RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (β = -21.77 mg/dL, 95% CI -33.22 to -10.33, P 

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PMID: 

Int J Mol Sci. 2019 Oct 8 ;20(19). Epub 2019 Oct 8. PMID: 31597233

Abstract Title: 

Protective Effects of Melatonin on the Skin: Future Perspectives.

Abstract: 

When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and pathways. Melatonin, a highly conserved ancient molecule, plays a crucial role in the maintenance of skin. As human skin has functional melatonin receptors and also acts as a complete system that is capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection. Below, we review the studies of new metabolic pathways involved in the protective functions of melatonin in dermal cells. We also discuss the advantages of the topical use of melatonin for therapeutic purposes and skin protection. In our view, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin and its metabolites, represent two of the most potent defense systems against external damage to the skin.

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PMID: 

J Obstet Gynaecol India. 2019 Oct ;69(5):436-443. Epub 2019 Apr 24. PMID: 31598047

Abstract Title: 

Effect of Melatonin on Blood Loss After Cesarean Section: A Prospective Randomized Double-Blind Trial.

Abstract: 

Background and Objectives: The similarities between the melatonin and oxytocin signaling could lead to increased contractility of myometrium. We designed this randomized double-blind, placebo-controlled trial to evaluate the efficacy of melatonin in reduction of blood loss during and after the lower segment cesarean section.Methods: One hundred and twenty patients who had been scheduled for cesarean section under spinal anesthesia were enrolled in the study. We randomly allocated them to one of the three following groups to receive either melatonin 3 mg (M), melatonin 6 mg (M), or placebo (P) sublingually 20 min before the surgery. The hemoglobin levels before and 12 h after surgery, the mean weight of the materials used in the operation time, the need for additional oxytocic therapy, and the incidence of adverse effects were probed and recorded.Results: There was a significant difference between the group Mand both Mand P in the mean weight of the materials ( = .024 and .041, respectively) and between Mand P groups in terms of mean decrease in hemoglobin during 12 h after cesarean section ( = .029).Conclusion: Using 6 mg melatonin, sublingually, as a premedication in patients undergoing cesarean section with spinal anesthesia could statistically reduce the amount of blood loss after the lower segment cesarean section, although it may not be clinically meaningful.: ACTRN12612000117819 and: NCT01572805.

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PMID: 

J Pineal Res. 2020 Jan ;68(1):e12615. Epub 2019 Nov 10. PMID: 31605630

Abstract Title: 

Melatonin attenuates epidermal growth factor-induced cathepsin S expression in ARPE-19 cells: Implications for proliferative vitreoretinopathy.

Abstract: 

Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti-invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)-induced proliferation of human ARPE-19 cells. Furthermore, melatonin reduced EGF-induced motility by suppressing cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV-CTSS) significantly inhibited EGF-induced cell motility when combined with melatonin. Epidermal growth factor induced the phosphorylation of AKT(S473)/mTOR (S2448) and transcription factor (c-Jun/Sp1) signaling pathways. Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.

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PMID: 

Bratisl Lek Listy. 2019 ;120(7):527-531. PMID: 31602989

Abstract Title: 

Melatonin treatment prevents carbon tetrachloride-induced acute lung injury in rats by mitigating tissue antioxidant capacity and inflammatory response.

Abstract: 

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue‑damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats.METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage.RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4.CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).

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PMID: 

Inflammation. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31728743

Abstract Title: 

Piceatannol Inhibits P. acnes-Induced Keratinocyte Proliferation and Migration by Downregulating Oxidative Stress and the Inflammatory Response.

Abstract: 

The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.

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PMID: 

Pak J Pharm Sci. 2019 Jul ;32(4):1453-1459. PMID: 31608862

Abstract Title: 

Antidiabetic and antioxidant effects of tannic acid and melatonin on streptozotocin induced diabetes in rats.

Abstract: 

The present investigation aimed to study the possible antidiabetic and related antioxidant potentials of tannic acid and melatonin in streptozotocin (STZ) induced diabetes in rats. Four groups of rats received intraperitoneal one dose of 50mg/kg body weight STZ for the induction of diabetes. The first group served as diabetic control group and received the vehicle. Four days after induction of diabetes, the remaining three groups received glibenclamide (6mg/kg/day), tannic acid (1 g/kg/day) and melatonin (10 mg/kg/day) for two weeks. A fifth group served as vehicle control group. At the end of the experimental period, blood samples and liver samples were collected for the determination of diabetes correlated biomarkers. Treatment of diabetic rats with tannic acid or melatonin attenuated most of the changes associated with STZ induced diabetes. The present results evidenced the beneficial effects of tannic acid and melatonin in diabetes management.

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PMID: 

EXCLI J. 2019 ;18:653-665. Epub 2019 Aug 21. PMID: 31611748

Abstract Title: 

Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats.

Abstract: 

Being one of the acute clinical problems, peripheral nerve injury can bring about a number of consequences including severe disability, reduced Quality of life (QOL) and immense costs. Currently, melatonin and curcumin are widely applied because of their immunomodulatory, anti-inflammatory, neuro-protective and antioxidant properties. The present study aims to compare the effects of melatonin and curcumin during light and dark periods on sciatic nerve crush injury repair. Accordingly, rats received IP injections of curcumin (100 mg/kg) and melatonin (10 mg/kg) over two periods of light (9:00 a.m.) and dark (9:00 p.m.) for 4 weeks. In order to evaluate rats, functional (walking track analysis and electrophysiological measurements), histomorphometric and gastrocnemius muscle mass investigations were administered. No statistically significant difference was identified between dark and light curcumin groups while curcumin groups displayed better results than did melatonin groups. In addition, dark melatonin group displayed better results than the light melatonin. On the whole, this study found that melatonin and curcumin can be used to quicken neural recovery and help treat nerve injury. It was also found that better neuroregeneration or nerve regeneration was induced when rats were treated by melatonin during the dark period while effects and injection time did not correlate in curcumin application.

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PMID: 

BMC Geriatr. 2019 Oct 16 ;19(1):272. Epub 2019 Oct 16. PMID: 31619178

Abstract Title: 

Melatonin for the prevention of postoperative delirium in older adults: a systematic review and meta-analysis.

Abstract: 

BACKGROUND: Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no pharmacological agents have compelling evidence to decrease the incidence of delirium. The purpose of this study was to assess whether perioperative melatonin decreases the incidence of delirium in older adults undergoing surgical procedures.METHODS: A systematic search using PubMed/Medline, Embase, PsycINFO, CINAHL, and references of identified articles published in English between January 1990 and October 2017 was performed. Two independent reviewers screened titles and abstracts, and then extracted data following a full-text review of included articles with consensus generation and bias assessment. Studies reporting outcomes for melatonin or ramelteon use to prevent delirium in postoperative hospitalized patients (mean age ≥ 50 years) were eligible for inclusion. Data were pooled using a fixed-effects model to generate a forest plot and obtain a summary odds ratio for the outcome of interest (delirium incidence). Cochran's Q and Ivalues were used to investigate heterogeneity.RESULTS: Of 335 records screened, 6 studies were selected for the qualitative analysis and 6 were included in the meta-analysis (n = 1155). The mean age of patients in included studies ranged from 59 to 84 years. Patients in intervention groups typically received melatonin or ramelteon at daily doses of two to eight milligrams around cardiothoracic, orthopedic, or hepatic surgeries for one to nine days, starting on the evening before or the day of surgery. The incidence of delirium ranged from 0 to 30% in the intervention groups versus 4-33% in the comparator groups, and was significantly reduced in the melatonin group, with a summary effect of the meta-analysis yielding an odds ratio of 0.63 (95% CI 0.46 to 0.87;0.006; I = 72.1%). A one study removed analysis reduced overall odds ratio to 0.310 (95% CI 0.19 to 0.50), while reducing heterogeneity (Cochran's Q = 0.798, I = 0.000).CONCLUSION: Perioperative melatonin reduced the incidence of delirium in older adults in the included studies. While optimal dosing remains an unanswered question, the potential benefit of melatonin and melatonin receptor agonists may make them a reasonable option to use for delirium prevention in older adults undergoing surgical procedures.

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PMID: 

Life Sci. 2019 Oct 13:116931. Epub 2019 Oct 13. PMID: 31618610

Abstract Title: 

Melatonin rescued methotrexate-induced spatial deficit and hyperhomocysteinemia and increased asymmetric dimethylarginine in plasma and dorsal hippocampus in developing rats.

Abstract: 

AIMS: With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice.MAIN METHODS: Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin.KEY FINDINGS: Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment.SIGNIFICANCES: Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress.

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