Decrease In Melatonin Levels Research Articles

The effect of exogenous melatonin on the dynamics of body weight and the level of Klotho protein in the blood of female rats subjected to prolonged dark deprivation

The study of the effect of exogenous melatonin (0.3 mg/kg, intragastrically in 2% starch mucus, 14-day course) on the dynamics of body weight and the level of Klotho protein in the blood of 4-month-old white mongrel female rats subjected to 30-day dark deprivation (light-dark mode 24/0 h, artificial lighting 300 Lux). It has been shown that prolonged dark deprivation leads to a decrease in the level of Klotho protein, which is a marker of premature aging; a decrease in melatonin levels, fluctuations in the rate of body weight gain in sexually mature female rats. Exogenous melatonin contributed to an increase in the level of Klotho protein and the restoration of melatonin levels in the blood serum of animals, as well as a decrease in body weight, which indicates its protective effect on the condition of animals with accelerated aging caused by dark deprivation.

The Role of Melatonin in the Inflammatory Process in Patients with Hyperglycemia and Leishmania Infection.

Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases.

The Role of Melatonin and Matrix Metalloproteinases in Breast Cancer Pathogenesis: A Comprehensive Review

Background: Breast cancer is a heterogeneous disease with molecular subtypes including Triple Negative Breast Cancer (TNBC), HER2/neu-positive, Luminal Type A, and Luminal Type B, each with unique clinical behaviors and therapeutic responses. This study investigates the role of melatonin, matrix metalloproteinases (MMPs), pro-inflammatory cytokines (IL6 and TNF-alpha), and lactate dehydrogenase (LDH) isoenzymes in breast cancer pathogenesis. Methods: Over three years, 171 breast cancer patients were studied. Blood and urine samples were collected to measure melatonin, MMPs, IL-6, TNF-alpha, LDH-1, and LDH-5 levels. Circulating tumor cells (CTCs) were isolated using density gradient centrifugation and immunomagnetic separation. Melatonin receptor expression on CTCs was analyzed by flow cytometry and immunocytochemistry. Plasma concentrations of melatonin were measured using high-performance liquid chromatography (HPLC), and MMPs, IL-6, TNF-alpha, LDH isoenzymes were quantified using enzyme-linked immunosorbent assays (ELISAs) and electrophoretic methods. Results: The expression of melatonin receptors was lowest in TNBC patients, higher in HER2/neu-positive and ER/PRnegative patients, and highest in Luminal Type A and B patients. TNBC patients exhibited elevated LDH-1 and inflammatory cytokines (IL-6, TNF-alpha), with significantly decreased melatonin levels. HER2/neu-positive patients showed elevated LDH5 and moderate decreases in melatonin. Luminal Type B and A patients had varying degrees of biomarker elevation and melatonin receptor expression. Discussion: The findings suggest a correlation between reduced melatonin signaling and aggressive breast cancer phenotypes, particularly TNBC. Elevated MMPs and pro-inflammatory cytokines underscore the role of inflammation and ECM degradation in cancer progression. Melatonin’s potential inhibitory effects on these pathways highlight its therapeutic promise. The combined assessment of melatonin, MMPs, cytokines, and LDH could guide personalized treatment strategies. Conclusion: This study underscores melatonin’s multifaceted role in breast cancer pathogenesis. Melatonin receptor expression, along with MMP, IL-6, TNF-alpha, and LDH levels, provides a detailed molecular landscape of breast cancer subtypes. Integrating melatonin supplementation into therapeutic regimens holds promise for improving outcomes, particularly inaggressive subtypes like TNBC. Further research and clinical trials are essential to validate these findings and develop effective melatonin-based therapies.

Overcoming poor ovarian response in assisted reproductive technology programs in patients of late reproductive age

Objective: to increase the effectiveness of in vitro fertilization in patients of late reproductive age by optimizing prepregnancy preparation for the IVF program.Materials and methods: The study included 67 patients of late reproductive age with a history of unsuccessful IVF attempts, divided into two groups at the second stage of the study, depending on the volume of prepregnancy preparation: group 1 (33 patients), group 2 (34 patients). The control group (50 patients) were healthy women of reproductive age. Immunohistochemical examination of the endometrium and microbiological examination of the uterine cavity, hormonal status of peripheral blood, study of the concentration of melatonin in peripheral blood and follicular fluid, antioxidant status of follicular fluid, expression of leukemia inhibitory factor (LIF) in the cervical secretion were performed.Results: in patients with age-related dysregulation of the hypothalamic-pituitary-ovarian axis and impaired fertile function, a systemic and local (in follicles) decrease in melatonin levels was revealed. The studied effects of melatonin suggested that its use in patients of late reproductive age with reduced follicular reserve and a "poor" response to ovarian stimulation may increase the effectiveness of in vitro fertilization (IVF).Conclusions: The inclusion in the pre-gravidar preparation of a complex of water-soluble polypeptide fractions of the epiphysis, stimulating the production of endogenous melatonin, made it possible to increase the effectiveness of IVF in patients by an average of 3.1 times according to the criterion of "clinical pregnancy" and 4.1 times according to the criterion of "live birth".

Neuroprotective Potential of Melatonin: Evaluating Therapeutic Efficacy in Alzheimer's and Parkinson's Diseases.

Decreased melatonin levels have been linked to both Alzheimer's disease (AD) and Parkinson's disease (PD), which are the two most prevalent neurodegenerative disorders. The development of sleep disorders is widespread in patients diagnosed with AD or PD. In this regard, calcification of the pineal gland, typically seen in the third decade, has been associated with a reduction in melatonin production. Recent studies have suggested that exogenous melatonin application can be utilized to treat sleep disorders in patients with neurodegenerative diseases. Furthermore, research has shown that deficiencies in melatonin levels in patients with AD or PD begin before a diagnosis of eitherdisease is made. These findings could encourage further research on melatonin as a potential biomarker for the diagnosis or a possible area for the early treatment of these diseases. Many clinical studies have also produced data denoting melatonin treatment as a method to reduce the detrimental neurocognitive effects of these diseases. Further research on the role of melatonin in neurodegenerative diseases could expand symptomatic and prophylactic treatment options for diseases such as AD and PD. This review investigates melatonin's physiological properties, its role in AD and PD, and current findings on its potential therapeutic benefits in AD and PD patients.

SLEEP DISTURBANCE AND DEPRESSIVE SYMPTOMS AMONG OLDER ADULTS: DO GENDER DIFFERENCES EXIST?

Abstract Sleep is a key part of a healthy lifestyle, but aging causes sleep problems by decreased melatonin levels. Sleep disturbance includes problems falling or staying asleep, too much sleep, or obstructive sleep apnea (OSA), the most common sleep-related breathing disorder in older adults. Thus, aging-related changes in sleep should be studied in various aspects of elderly’s health such as physical, mental, and cognitive health. As part of that, this study aims to (1) examine the connection between sleep disturbance and depressive symptoms and (2) investigate whether gender differences exist. Participants were Korean adults aged 65 and older (N=1,316) from the 2020 Korean National Health and Nutrition Examination Survey. The survey measured sleep disturbances (OSA, insomnia, hypersomnia), depressive symptoms, and sociodemographic characteristics. Hierarchical multiple regression analysis was conducted to examine whether sleep disturbances influence depressive symptoms and test the interaction between sleep disturbance and gender. Results revealed that after adjusting for covariates, those with more risk factors for OSA (B=1.056, p=.000) or with insomnia (B=1.527, p=.000) were more likely to have greater depressive symptoms than their counterparts. Additionally, the relative influences of OSA (B=1.295, p=.000) or insomnia (B=.965, p=.023) on depressive symptoms were contingent upon gender. However, no correlation was observed between hypersomnia and depressive symptoms. Although both OSA and insomnia are risk factors for depressive symptoms, older women with OSA or insomnia showed more severe depressive symptoms than older men with OSA or insomnia. Findings suggest the need to make sophisticated approaches considering homogeneity and heterogeneity within older adults.

Influence of different LED wavelengths on retinal melatonin levels - A rodent study

BackgroundRetinal melatonin is crucial for neuroprotection. Exposure to light-emitting diodes (LEDs) affects retinal neurons, possibly influencing retinal melatonin levels. Hence, we aimed to quantify the retinal melatonin level with different LED wavelengths. MethodA total of 24 Sprague Dawley (SD) male rats were divided into four groups (n = 6 in each group) as normal controls (NC), blue light (BL), white light (WL), and yellow light (YL). The rats in the experimental groups were exposed to different wavelengths of LEDs for 28 days (12:12 h light-dark cycle) with uniform illumination of 450–500 lx. Following exposure, the rats were subjected to behavioral tests such as passive avoidance and elevated plus maze tests. Following the behavior tests, the rats were sacrificed, eyes were enucleated, and retinal tissue was stored at −80 °C. The homogenized retina was used for reactive oxygen species (ROS) and melatonin quantification using an enzyme-linked immunosorbent assay (ELISA) kit. ResultsPassive avoidance test revealed a significant difference across the groups (p < 0.0004). The BL exposure group demonstrated increased latency to enter the dark compartment (DC) and impaired motor memory. The elevated plus maze test revealed a significant difference across all the groups (p < 0.012), where the time spent in the closed arm was greater in the BL exposure group. Comparison of ROS levels revealed a significant difference across the groups (p < 0.0001), with increased nitric oxide concentrations in the experimental groups. Melatonin levels were significantly decreased in the light exposure groups (p < 0.0001) compared to the NC group. ConclusionCumulative exposure to different LED wavelengths resulted in increased anxiety with impaired motor activity. This was also complemented by the addition of oxidative stress leading to decreased melatonin levels in the retina, which might trigger retinal neuronal damage.

EFFECT OF MELATONIN ON THE LEVEL OF CYTOKINES IN PREECLAMPSIA

Introduction. The literature reports a decrease in melatonin levels in preeclampsia, when the degree of decrease correlates with the severity of the process, as well as a decrease in the expression of melatonin receptors in the placental tissue in case of fetal growth restriction.Regarding changes in the cytokine profile in PE: there is evidence that the levels of proinflammatory cytokines, namely TNF-α and IL-6, increase in preeclampsia, while the concentrations of anti-inflammatory cytokines, namely IL-4 and IL-10, decrease. Melatonin, on the contrary, reduces the secretion of proinflammatory cytokines, in particular TNF-α, and increases the production of anti-inflammatory cytokines, namely IL-10. Therefore, normalization of melatonin levels may be a promising direction in the treatment of PE in pregnant women.Objective of the study. Assess the pathogenetic mechanisms of complications arising from a decrease in melatonin, and, in particular, find out more about the changes in melatonin, IL-6 and IL-10, determine the correlation between them.Material and research methodsThe study conducted at the Department of Pregnancy Pathology of the Chernivtsi Regional Perinatal Center, involved 32 women whose pregnancy was complicated by preeclampsia. The control group consisted of 33 women with uncomplicated pregnancies observed in the antenatal clinic of the Chernivtsi Regional Perinatal Center.The patient's informed consent form and the patient's examination card were approved by the Biomedical Ethics Committee of Bukovinian State Medical University (BSMU) of the Ministry of Health of Ukraine (Chernivtsi). The work was guided by the general provisions of the Declaration of Helsinki "Recommendations for Physicians for Biomedical Research Involving Human Subjects" (1964), the World Medical Association on Ethical Principles for Scientific Medical Research Involving Human Subjects (1964-2000), considering the requirements of Directive 2001/20/EC of the European Parliament and of the Council, ICH GCP, the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009.Statistical data were calculated using MedCalc software developed by MedCalc Software (Ostend, Belgium). The results were evaluated using the Mann-Whitney U-test for small groups. The P value of &lt;0.05 was considered valid. Correlation and regression statistical evaluations were also performed using the aforementioned software.R&amp;D «Preservation and restoration of reproductive health of women and girls in obstetric and gynecological pathology». State registration number: 0121U110020. Terms of execution: 01.2021–12.2025 yy.Research results. The level of melatonin in venous blood taken from women with diagnosed PE was significantly lower (p=0.029), as well as levels of placental growth factor PlGF (p&lt;0.0001), compared to healthy women. In our study we also found that the concentrations of both proinflammatory IL-6 and anti-inflammatory IL-10 were elevated in women with PE compared to women with uncomplicated pregnancies. We performed a prognostic assessment of the impact of the biochemical parameters we studied on the outcome of pregnancies in the examined patients. Melatonin, if present in the blood of a pregnant woman in a concentration higher than the threshold values we established (6.71 pg/ml), reduces the chances of clinical manifestations of severe preeclampsia with a high degree of reliability (p=0.00173). We assume that placental dysfunction in particular leads to impaired synthesis of the antioxidant melatonin, which causes disorders in the tissues of the mother, placenta and fetus and, as a result, provokes clinical manifestations of preeclampsia. The condition of the placenta also worsens the subclinical inflammatory process, as evidenced by an increase in IL-6 levels in patients with diagnosed preeclampsia; an increase in IL-10 in the study group, in our opinion, is a kind of compensatory reaction that prevents preterm labour. In women with pregnancies complicated by preeclampsia, melatonin is a prognostic criterion for delivery before 38 weeks of gestation, and this delivery is mainly associated with the progression of preeclampsia to its severe stage. In the group of patients with uncomplicated pregnancy, proinflammatory interleukin-6 is predictive of spontaneous onset of labour before 38 weeks of gestation. Placental growth factor PlGF was a predictor of the birth of children with a body weight of less than 3000 g in both study groups.Conclusions. Concentrations of melatonin and of placental growth factor in venous blood in women whose pregnancy was complicated by preeclampsia in the third trimester of pregnancy are significantly lower compared to uncomplicated pregnancies. On the other hand, the levels of proinflammatory IL-6 and anti-inflammatory IL-10 were significantly increased in the group of patients with diagnosed preeclampsia compared with normal pregnancy.

Изменение концентрации мелатонина при прогрессировании катаракты

Purpose. To establish the relationship between melatonin level in the blood serum and the lens in patients with different degrees of cataract progression. Material and methods During the study, the following groups of patients were formed: group 1 – initial cataract, group 2 – immature cataract, group 3 – mature cataract and group 4 – complicated initial cataract with type 2 diabetes mellitus. All patients were surveyed. Considering the fact that melatonin secretion depends on a daily rhythm, the sampling of biomaterial for analysis was carried out at the same time during a planned surgical intervention. Melatonin content was determined by enzyme immunoassay using the commercial Human MT (Melatonin) ELISA Kit. Results. The study did not reveal statistically significant changes in the level of melatonin in the blood serum of patients with different levels of cataract progression. However, there was a trend towards lower melatonin values in the group of patients with immature and mature cataract, relative to patients with initial cataract. When comparing the group of patients with mature cataract relative to patients with initial cataract, there was a decrease in melatonin levels by 45 % (p ≤ 0.05). The level of melatonin in the lens of patients with cataract complicated by diabetes mellitus was lower by 63 % (p ≤ 0.01) compared to patients with uncomplicated initial cataract. Conclusion. It was found that the level of melatonin in the lens significantly depends on the degree of cataract progression. Cataracts complicated by diabetes mellitus were characterized by minimal values of melatonin in the lens. The obtained data show the relevance of further research to assess the role of melatonin in various ophthalmic pathologies. Keywords: melatonin, cataract, eye lens

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review.

The incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved. In this review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023. Prolonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine's ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep-wake rhythm transitions. Our review revealed that the functional and structural abnormalities of sleep-wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.

Multiomics analysis of human peripheral blood reveals marked molecular profiling changes caused by one night of sleep deprivation.

Sleep insufficiency is associated with various disorders; the molecular basis is unknown until now. Here, 14 males and 18 females were subjected to short-term (24h) sleep deprivation, and donated fasting blood samples prior to (day 1) and following (days 2 and 3) short-term sleep deprivation. We used multiple omics techniques to examine changes in volunteers' blood samples that were subjected to integrated, biochemical, transcriptomic, proteomic, and metabolomic analyses. Sleep deprivation caused marked molecular changes (46.4% transcript genes, 59.3% proteins, and 55.6% metabolites) that incompletely reversed by day 3. The immune system in particular neutrophil-mediated processes associated with plasma superoxidase dismutase-1 and S100A8 gene expression was markedly affected. Sleep deprivation decreased melatonin levels and increased immune cells, inflammatory factors and c-reactive protein. By disease enrichment analysis, sleep deprivation induced signaling pathways for schizophrenia and neurodegenerative diseases enriched. In sum, this is the first multiomics approach to show that sleep deprivation causes prominent immune changes in humans, and clearly identified potential immune biomarkers associated with sleep deprivation. This study indicated that the blood profile following sleep disruption, such as may occur among shift workers, may induce immune and central nervous system dysfunction.

Peculiarities of circadian regulation of the thyroid gland

Circadian rhythmicity is an autonomous period of organ cells’ functioning that is controlled by feedback mechanisms and specific genes. The thyroid gland, as a peripheral organ of the endocrine system, is subordinate to the adenohypophysis and pineal gland. Melatonin, as one of the main mediators of circadian influence, is well known for its antitumor and regulatory effects on a number of tissues, but its relationship with the hormone-producing activity of the thyroid gland has not been sufficiently studied. The purpose of the work was to analyze the current data on circadian regulation of the thyroid gland by examining evidence-based scientific publications from open databases over the past five years. Melatonin-producing pineal cells possess the homeotic genes Otx2 and Crx whose deactivation leads to a significant decrease in melatonin production by the pineal gland. In addition to pineal cells, melatonin can be synthesized by adenohypophysis-independent parafollicular cells. The effect of melatonin on thyrocytes is provided by binding to MT1 receptors and affecting the expression of thyroglobulin, RX-8, and TTF-1 (NKX2-1) genes. Under conditions of short photoperiod, melatonin inhibits the production of thyroid-stimulating hormone (TSH) β, which, in turn, acts on hypothalamic tanycytes by regulating the balance of deiodinase (Dio2/Dio3). This leads to a well-regulated seasonal control of the release of the thyroid hormone triiodothyronine. Conclusions. Circadian regulation of thyrocyte activity occurs under the influence of melatonin, which is secreted by pinealocytes and sometimes by parafollicular cells. TSH is secreted with a certain circadian periodicity under the influence of the activation of chronorhythmic genes. Hormone replacement therapy should be aimed not only at restoring the levels of pituitary hormones, but also at restoring the biological rhythm of TSH secretion. Melatonin affects the circadian work of thyrocytes, which is proven by determining the expression of the chronorhythm genes Bmal-1, Dio2, TTF-1. In thyroid pathology, there is a violation of circadian rhythms, a decrease in melatonin levels, and a decrease in the expression of Clock genes.

An array of occupationally exposure to extremely low frequency electromagnetic fields and light at night on melatonin and related oxidative stress in human subjects

During one decade, an increasing percentage of world population has to be attributed to an array of environmental, health and lifestyle factors. The potential effect of extremely low frequency electromagnetic fields (ELF-EMFs) emitted from electrical and various electrical devices in the occupational environment and light at night (LAN) to elicit biological response are a major concern for the public and scientists. Controversial genetic and oxidative stress effects have been reported by these polluted environments. Hence this study was undertaken with a purpose to evaluate melatonin hormone and oxidative stress markers in exposure workers along with cumulative effects of smoking and drinking. The study subjects (n=342) included night shift workers for more than 2 years with age, gender, socioeconomic status matched non-exposure controls (n=150). Self-reported symptoms were sought using questionnaire. Plasma Melatonin was evaluated using radioimmuno assay. Oxidative stress was estimated by measuring plasma malondialdehyde (MDA), serum nitric oxide (NO) and erythrocyte catalase levels. When the data of exposed subjects was analyzed, a significant decrease in melatonin levels was observed. Plasma MDA levels demonstrated a significant increase in one sub-group. The serum NO levels and erythrocyte catalase levels shows a significant increase. The cumulative effect of a chemical agent or environmental pollutant could be a possible contributor in enhancing the adverse effect of extremely low frequency electromagnetic fields. Certain caution is necessary.

Peculiarities of melatonin levels in preterm infants.

Melatonin plays an important role in organism functioning, child growth, and development. Of particular importance is melatonin for preterm infants. The aim of our research was to study the peculiarities of melatonin levels depending on various factors in preterm infants with gestational age (GA) of less than 34weeks. The study involved 104 preterm infants with GA less than 34weeks who were treated in the neonatal intensive care unit (NICU). The level of melatonin in urine samples was determined by an enzyme-linked immunosorbent assay. Melatonin concentration was significantly lower in extremely and very preterm infants compared to moderate preterm (3.57 [2.10; 5.06] ng/ml vs. 4.96 [3.20; 8.42] ng/ml, p = 0.007) and was positively correlated with GA (Spearman r = 0.32; p < 0.001). Positive correlations were revealed between melatonin levels and Apgar scores at the 1st(Spearman r = 0.31; p = 0.001) and 5thminutes after birth (Spearman r = 0.35; p < 0.001). Melatonin levels were lower in newborns with respiratory distress syndrome (p = 0.011). No significant correlations were found between melatonin concentration and birth weight (Spearman r = 0.15; p = 0.130). There were no associations of melatonin concentrations and mode of delivery (p = 0.914), the incidence of early-onset sepsis (p = 0.370) and intraventricular hemorrhages (p = 0.501), and mechanical ventilation (p = 0.090). The results of multiple regression showed that gestational age at birth was the most significant predictor of melatonin level in preterm infants (B = 0.507; p = 0.001). Gestational age and the Apgar score were associated with decreased melatonin levels in preterm infants. The level of melatonin in extremely and very preterm infants was lower compared to moderate preterm infants.

Disruption of regulatory mechanisms as a stress factor for patients with metabolic syndrome

Introduction. Throughout history, humanity has lived and developed in accordance with its biological rhythms, which provided the adaptation of the body to the factors of external and internal environment, ensuring the normal synchronous functioning of all its components.The purpose of this work was to study the stressful influence of circadian rhythms disturbance on patients with metabolic syndrome (MS) under conditions of dark deprivation.Material and methods of investigation. We selected patients with MS and disturbed circadian rhythms – a total of 102 people (all men) from among those who constantly work at night, in whom a decrease in melatonin levels was recorded at the preliminary stage. According to the set objectives, 102 patients (young age according to WHO criteria) were divided into three groups of 33, 37 and 32 persons according to the criterion "duration of influence of dark deprivation and MS history duration": 0–5, 5–10 and over 10 years. In the first group the mean age was 30.1 ± 1.4 years, in the second group – 36.5 ± 1.5 years, in the third group the mean age did not exceed 40.3 ± 0.9 years. Melatonin levels (as confirmation of circadian rhythm disturbances) in blood serum were studied in all study participants using Melatonin ELISA immunoassay kit (IBL, Germany). Results and discussion. Normally, when blood cortisol is measured before 10 a.m., its average value varies in a wide range from138 to 635 nmol/l. The increase up to 700 nmol/l is admitted, which is regarded as a negative influence of external factors during the examination. However, one should keep in mind that during evening measurements, cortisol levels in men may normally decrease to 80 nmol/l.Conclusions. Thus, dark deprivation in patients with metabolic syndrome leads to the formation of a stress response. Maximum changes occur after 10 years of disturbance of regulatory mechanisms and lead to a pronounced imbalance between the sympathetic and parasympathetic nervous system, increased vascular tone and changes in the profile of blood pressure during the day towards the predominance of Non-dippers and Night-peers, which increases the risk of progression of metabolic syndrome symptoms.

Impact of circuit rhythms disturbances on the clinical picture of the disease in patients with metabolic syndrome

The purpose of this study was to evaluatey the effect of dark deprivation of various durations on the course of the metabolic syndrome (MS).Material and research methods. To achieve this aim, based on WHO criteria, we selected patients with MS and disturbed circadian rhythms – a total of 102 people (all men) from among people who constantly work at night, in whom a decrease in melatonin levels was recorded at a preliminary stage. In accordance with the tasks set, 102 patients (all men) of working age (young age according to WHO criteria) were divided into three groups of 33, 37 and 32 people, respectively, according to the criterion "duration of work at night and duration of history of MS": 0–5, 5–10 and over 10 years. In the first group, the mean age was 30.1 ± 1.4 years; in the second group, the mean age was 36.5 ± 1.5 years; in the third group, the mean age did not exceed 40.3 ± 0.9 years. As a control group, 45 patients with MS were examined, comparable with the main groups in terms of background pathology and age and different duration of MS history.Results. It was found that the main symptom of MS - abdominal type of obesity (waist circumference more than 80 cm for men) was detected in 100% of patients of the main and control groups of observation. At the same time, it was found that the severity of abdominal obesity is combined with an increase in body mass index (BMI) and tends to increase in patients in the main groups, compared with patients from the control group. In the control group, 35.5% of the examined patients had grade 1-2 hypertension, and another 15.6% had elevated normal blood pressure.Conclusions: In patients with MS, against the background of violations of regulatory mechanisms, the disease is more severe than in patients with a similar history of MS, but without violations of circadian rhythms. The severity of the course of MS against the background of a decrease in the level of melatonin increases with the duration of the violation of regulatory mechanisms.

The physiological role of melatonin in oxidative stress during the embryonic period of development

Introduction. Melatonin, being a powerful endogenous antioxidant, provides healthy course of pregnancy and childbirth. Decrease of melatonin levels in blood correlates with severity of preeclampsia. Currently, melatonin is viewed as a perspective antioxidant, able to improve mother’s condition during preeclampsia and protect fetus from unfavorable intrauterine environment.The objective was to study melatonin effects on remodeling of chicken embryo heart tissue under normal conditions and under oxidative stress model.Materials and methods. The study was performed using organotypic culture of heart tissue of 10–12-day-old chicken embryos. Oxidative stress was modeled by adding epinephrine 10–4 М or homocysteine thiolactone 10–3 М to culture medium.Results. The trophotropic effects of melatonin was detected at a concentration of 10–6 M. Drug stimulated heart tissue explants’ growth on 20 %. Epinephrine showed cardiotoxic effects at concentrations of 10–4 and 10–6 М. Melatonin (10–6 М) neutralized cardiotoxic effects of epinephrine (10–4 M). Cardiotoxic effects of homocysteine thiolactone (10–3 М) preserved in presence of melatonin (10–6 М).Conclusion. During embryonic period, melatonin neutralizes cardiotoxic effects of oxidative stress caused by a high concentration of epinephrine, but not by homocysteine thiolactone.

PINEAL GLAND AND PREECLAMPSIA – A MODERN VIEW OF THE PROBLEM (LITERATURE REVIEW)

Preeclampsia is a complex pathological process which development signifi cantly depends on a decrease in melatonin levels of pregnant women as a result of the pineal gland and placenta dysfunction. The most important hormone of the pineal gland is melatonin, which is a derivative of tryptophan – an essential amino acid. Melatonin is a powerful natural antioxidant. When it’s levels are decreased, there is a risk of preeclampsia progression as a pathological condition of pregnant women, accompanied by high blood pressure, systemic multiple- organ failure and even cerebral edema and convulsions.Thus, although preeclampsia is considered a disease of the mother, it should rather be considered as a pathological condition of the placenta that aff ects both mother’s and fetus health. As the key factor of placental diorders is an oxidative stress, many researchers consider melatonin to be a potentially useful option for treating preeclampsia. It is noted that pregnant women with preeclampsia have a decrease in nocturnal concentrations of melatonin in comparison with healthy pregnant women that may indicate about pineal gland dysfunction in preeclampsia. Therefore, the normalization of melatonin levels may be a promising direction in the treatment of pregnant women with preeclampsia.

Constant light exposure and/or pinealectomy increases susceptibility to trichloroethylene-induced hepatotoxicity and liver cancer in male mice

Exposure to light at night, pineal gland impairment, and the environmental pollutant trichloroethylene (TCE) have serious implications for health and contribute to illness, including liver cancer. The adverse effect of the association of continuous exposure to light with decreased melatonin levels and TCE-induced toxicity is not disclosed in target organs. This work explored the role of light and pineal impairment in increasing susceptibility to liver toxicity and cancer upon exposure to TCE. Male albino mice were divided into groups as follows: control group (12-h light/12-h dark cycle), constant light (24-h light), pinealectomized (Pnx) mice, sham surgically treated group, TCE-treated groups subjected to two doses (500 and 1000 mg/kg) at two different light regimens, and combination of Pnx and TCE-treated mice kept at a 12-h light/12-h dark cycle. Melatonin levels were significantly decreased in both Pnx mice and TCE-treated animals at both light regimens. Aspartate transaminase, alanine aminotransferase, activities, and serum bilirubin levels were significantly elevated, whereas albumin levels were markedly decreased in Pnx mice, TCE-treated mice, and the combination group. Histopathological investigations reflected changes in liver function parameters indicating liver injury and induction of cancer. These effects were accompanied by significant increase of the liver cancer biomarker alpha-fetoprotein and the expression of the metastatic markers CD44, TGFβ-1, and VEGF, along with increased oxidative stress indicators and inflammatory cytokines (IL-6, IL-1β, and TNF-α) in both Pnx and TCE-treated mice and the combination group at both light regimens. Taken together, our findings indicated that low melatonin levels, exposure to constant light, and the combination of both factors increases susceptibility to the toxic and carcinogenic effects of TCE on the liver.

Seungmagalgeun-Tang, a Traditional Herbal Formula, Alleviates Skin Inflammation and Depression-Like Behavior in Atopic Dermatitis Mice under Sleep Deprivation Conditions.

Atopic dermatitis (AD) is a common inflammatory skin disease, which can be worsened under sleep deprivation (SD) conditions. This study investigated the efficacy and the mechanism of action of the traditional herbal formula Seungmagalgeun-tang (SMGGT) on the inflammation and behavioral changes in a mouse model of AD exposed to SD. SMGGT decreased levels of IgE, TNF-α, IL-4, IL-13, and mast cell infiltration and reduced the expression of CD3 in the mouse skin. SMGGT also reversed the SD-induced increase in corticosterone and decrease in melatonin level. Furthermore, SMGGT reduced the immobility time in the tail suspension test significantly. HaCaT cells and HMC-1 cells were used to investigate the effects of SMGGT on cell signaling pathways. In TNF-α/IFN-γ (TI) treated HaCaT cells, SMGGT reduced production of TARC/CCL17 and MDC/CCL22 and suppressed the p38 MAPK, STAT1, and NF-κB pathways. In substance P (SP)/CRH-stimulated HMC-1 cells, SMGGT decreased VEGF production and inhibited ERK phosphorylation. Network pharmacology and molecular docking analysis revealed that puerarin and paeoniflorin might contribute to the effects of SMGGT by targeting several AD-related molecules and pathways. Puerarin and paeoniflorin exerted anti-inflammatory effects by decreasing production of MDC/CCL22 and IL-6 in TI-treated HaCaT cells and VEGF production in SP/CRH-stimulated HMC-1 cells. This study suggests that SMGGT with puerarin and paeoniflorin as main bioactive components alleviates skin inflammation and depression-like behavior in a sleep-deprived mouse model of AD.