The circadian clock is one of the most important homeostatic systems regulating the majority of physiological functions. Its proper development contributes significantly to the maintenance of health in adulthood. Methadone is recommended for the treatment of opioid use disorders during pregnancy, increasing the number of children prenatally exposed to long-acting opioids. Although early-life opioid exposure has been studied for a number of behavioral and physiological changes observed later in life, information on the relationship between the effects of methadone exposure and circadian system development is lacking. Using a rat model, we investigated the effects of prenatal and early postnatal methadone administration on the maturation of the circadian clockwork in the suprachiasmatic nucleus (SCN) and liver, the rhythm of aralkylamine N-acetyltransferase (AA-NAT) activity in the pineal gland, and gene expression in the livers of 20-day-old rats. Our data show that repeated administration of methadone to pregnant and lactating mothers has significant effect on rhythmic gene expression in the SCN and livers and on the rhythm of AA-NAT in the offspring. Similar to previous studies with morphine, the rhythm amplitudes of the clock genes in the SCN and liver were unchanged or enhanced. However, six of seven specific genes in the liver showed significant downregulation of their expression, compared to the controls in at least one experimental group. Importantly, the amplitude of the AA-NAT rhythm was significantly reduced in all methadone-treated groups. As there is a strong correlation with melatonin levels, this result could be of importance for clinical practice.
- MeSH
- cirkadiánní rytmus fyziologie MeSH
- epifýza mozková * metabolismus MeSH
- krysa rodu rattus MeSH
- laktace MeSH
- melatonin * farmakologie MeSH
- methadon metabolismus farmakologie MeSH
- nucleus suprachiasmaticus fyziologie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Melatonin has been reported to cause myocardial electrophysiological changes and prevent ventricular tachycardia or fibrillation (VT/VF) in ischemia and reperfusion. We sought to identify electrophysiological targets responsible for the melatonin antiarrhythmic action and to explore whether melatonin receptor-dependent pathways or its antioxidative properties are essential for these effects. Ischemia was induced in anesthetized rats given a placebo, melatonin, and/or luzindole (MT1/MT2 melatonin receptor blocker), and epicardial mapping with reperfusion VT/VFs assessment was performed. The oxidative stress assessment and Western blotting analysis were performed in the explanted hearts. Transmembrane potentials and ionic currents were recorded in cardiomyocytes with melatonin and/or luzindole application. Melatonin reduced reperfusion VT/VF incidence associated with local activation time in logistic regression analysis. Melatonin prevented ischemia-related conduction slowing and did not change the total connexin43 (Cx43) level or oxidative stress markers, but it increased the content of a phosphorylated Cx43 variant (P-Cx43368). Luzindole abolished the melatonin antiarrhythmic effect, slowed conduction, decreased total Cx43, protein kinase Cε and P-Cx43368 levels, and the IK1 current, and caused resting membrane potential (RMP) depolarization. Neither melatonin nor luzindole modified INa current. Thus, the antiarrhythmic effect of melatonin was mediated by the receptor-dependent enhancement of impulse conduction, which was associated with Cx43 phosphorylation and maintaining the RMP level.
- MeSH
- antiarytmika farmakologie terapeutické užití MeSH
- kardiomyocyty metabolismus MeSH
- konexin 43 * metabolismus MeSH
- krysa rodu rattus MeSH
- melatonin * farmakologie terapeutické užití MeSH
- melatoninové receptory metabolismus MeSH
- srdeční arytmie farmakoterapie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We aimed to investigate the effects of melatonin and resveratrol on diabetes-related papillary muscle dysfunction and structural heart disorders. The protective effect of resveratrol and melatonin supplementation on cardiac functions was investigated in a diabetic elderly female rat model. 16-month-old rats (n=48) were allocated into 8 groups. Group1: Control, Group2: Resveratrol Control, Group3: Melatonin Control, Group4: Resveratrol and Melatonin Control, Group5: Diabetes, Group6: Diabetes Resveratrol, Group7: Diabetes Melatonin, Group8: Diabetes Resveratrol and Melatonin. Streptozotocin was injected intraperitoneally to the rats for experimental diabetes induction. Thereafter, resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for 4 weeks. Resveratrol and melatonin had a protective effect on the contractile parameters and structural properties of the papillary muscle, which was impaired by diabetes. it has been presented that diabetes impairs the contractile function of the papillary muscle for each stimulus frequency tested and the responses obtained as a result of Ca+2 uptake and release mechanisms from the Sarcoplasmic reticulum, and it has been observed that these effects are improved with resveratrol and melatonin injection. The decrease in myocardial papillary muscle strength in the diabetic elderly female rat can be reversed with the combination of resveratrol, melatonin and resveratrol+melatonin. Melatonin+resveratrol supplementation is no different from melatonin and/or resveratrol supplementation. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in a diabetic elderly female rat model.
- MeSH
- experimentální diabetes mellitus * komplikace farmakoterapie MeSH
- krysa rodu rattus MeSH
- melatonin * farmakologie terapeutické užití MeSH
- nemoci srdce * MeSH
- papilární svaly MeSH
- resveratrol farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in patients with diabetes mellitus (DM). The night's decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM. METHODS: Platelet aggregation was measured in blood samples from healthy individuals (n = 15) and type 2 DM patients (n = 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations. RESULTS: In healthy individuals, melatonin inhibited platelet aggregation in both higher (10-5 M) and lower concentrations (10-9 M) induced by ADP, ASPI, and TRAP (p < 0.001, p = 0.002, p = 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (p = 0.005, p = 0.045 and p = 0.048, respectively). CONCLUSION: Platelet aggregation was inhibited by melatonin in healthy individuals. In-vitro antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.
- MeSH
- adenosindifosfát farmakologie MeSH
- agregace trombocytů fyziologie MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- infarkt myokardu * MeSH
- inhibitory agregace trombocytů farmakologie terapeutické užití MeSH
- lidé MeSH
- melatonin * farmakologie terapeutické užití MeSH
- trombocyty fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Although clinical research is still going on to determine any relationship between vitamin D and sleep regulation, only few studies have identified the role of vitamin D metabolism in sleep disorders. The current study aims to examine the incidence of vitamin D deficiency/insufficiency in the sample group and its effects on sleep quality and melatonin level. METHODS: A cross-sectional study was designed. A total of 79 women aged 18-49 years who applied to the research and training hospital between 1 October and 30 November 2021 participated in the study. Data were collected using a socio-demographic questionnaire prepared by the authors and the Pittsburgh Sleep Quality Index (PSQI). Blood samples were taken from the participants, also, 25-OH-vitamin D3 and melatonin levels in serum samples were measured by ELISA. RESULTS: The participants (n = 79) were aged 29.61 ± 11.14 years. The mean total PSQI scores of the participants were calculated as 5.77 ± 2.70. We determined that 64.6% of the participants had vitamin D deficiency, 21.5% had vitamin D insufficiency, and 13.9% of the participants were vitamin D sufficient. The mean melatonin level was found to be 24.77 ± 27.77 ng/L. We determined that an increase in the melatonin levels decreases the risk of vitamin D deficiency. Besides, our findings showed a good positive correlation between serum melatonin and 25 OH vitamin D3 levels (r = 0.544, p < 0.001). CONCLUSION: Our results indicate that the correction of vitamin D insufficiency can positively affect melatonin levels, therefore, it may positively contribute to the treatment of sleep disorders related to melatonin deficiency.
Poruchy spánku patří k častým problémům ve stáří. Benzodiazepinová i nebenzodiazepinová hypnotika jsou v seniorském věku riziková z důvodu navození závislosti a závažných nežádoucích účinků. Jedním z léků užívaných k léčbě nespavosti je melatonin, endogenní mediátor cirkadiánního rytmu. Je to látka bezpečná a pro seniory vhodnější než běžná hypnotika. Lze jej doporučit u seniorů bez kognitivního deficitu či s lehkým kognitivním deficitem; u lidí s již rozvinutou demencí melatonin významný vliv na zlepšení spánku zřejmě nemá. Případné neuroprotektivní účinky melatoninu na lidech bude ještě nutné prokázat v randomizovaných studiích.
Sleep disorders are common among seniors. Benzodiazepine and nonbenzodiazepine hypnotics are not recommended for seniors because of the risk of addiction and serious adverse effects. Melatonin is an endogenous mediator of circadian rhythm and it can be used as an effective hypnotic. It has no serious adverse effects and therefore it is more suitable for seniors. Melatonin can be recommended to promote sleep by seniors without cognitive impairment and those with mild cognitive impairment; for people with advanced dementia melatonin has not an apparent hypnotic effect. Eventual neuroprotective effects of melatonin should be verified in randomized controlled trials.
Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).
- MeSH
- antidepresiva terapeutické užití MeSH
- benzodiazepiny terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- melatonin * terapeutické užití farmakologie MeSH
- poruchy iniciace a udržování spánku * terapie farmakoterapie MeSH
- spánek MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- MC3T3-E1,
- MeSH
- antihypertenziva škodlivé účinky MeSH
- diabetes mellitus 1. typu komplikace MeSH
- fraktury páteře ekonomika epidemiologie MeSH
- kostní denzita účinky léků MeSH
- krevní tlak účinky léků MeSH
- lidé MeSH
- melatonin fyziologie terapeutické užití MeSH
- menopauza MeSH
- nemoci cév komplikace patofyziologie MeSH
- osteologie * trendy MeSH
- osteoporóza etiologie komplikace patofyziologie prevence a kontrola MeSH
- plošný screening ekonomika MeSH
- riziko MeSH
- stárnutí patologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- souhrny MeSH
- MeSH
- fyziologie kožního systému MeSH
- fyziologie kůže * MeSH
- lidé MeSH
- melatonin fyziologie MeSH
- mikrobiota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Melatonin is a simple compound called N-acetyl-5-methoxy tryptamine and is known as a hormone controlling the circadian rhythm. Melatonin is produced by the human body naturally. The production of melatonin increases in the evening, causing a state of sleep at night and wakefulness during the day. Melatonin interacts with melatonin receptors MT1 and MT2, but it was revealed that melatonin is a strong antioxidant and it also has a role in the regulation of the cell cycle. Melatonin is now used as a medicine to treat some types of sleep disorders. Moreover, recent research suggests that it can also be utilized for other purposes, such as prevention from chemical exposure and treatment of various diseases, including cancer, neurodegenerative disorders, etc. This review summarizes the basic facts and direction of the current research on melatonin. The existing literature was scrutinized for this review.
