Antioxidant Properties Of Melatonin Research Articles

Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20g were divided into five groups: control, 5-FU (50mg/kg), 5-FU + MEL (2.5, 5 & 10mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.

Melatonin protects against sarcopenia in middle-aged mice.

Sarcopenia is a common age-related disease. Melatonin (MEL) is an age-related endocrine hormone, which displays a crucial role in resisting oxidative stress during aging. Importantly, the antioxidant properties of MEL can be mediated by mitochondria. Therefore, we wondered whether MEL could mitigate oxidative stress caused by mitochondria in sarcopenia. The middle-aged mice were administered 5 mg/kg/d and 10 mg/kg/d of MEL for 2 months. Young mice were used as the control group. After treatment with MEL, the grip strength of the fore/hind limbs, running time, and distance were elevated, and the weights of the gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) were enhanced in middle-aged mice. Additionally, MEL was observed to alleviate histological damage and increase the cross-sectional area of muscle fibers in GA tissues of middle-aged mice. Furthermore, following MEL treatment, there was an increase in the percentage and size of normal mitochondria as well as mtDNA copy number but a reduction in the levels of malondialdehyde (MDA), protein carbonyl, and reactive oxygen species (ROS) in the GA tissues of middle-aged mice. At the molecular level, MEL repressed the levels of ATROGIN-1, muscle RING-finger protein-1 (MURF-1), and the ratio of p-P38/P38, but elevated the expression of cytochrome c oxidase subunit 4 (COX4), cystatin C (CYTC), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the GA tissues of middle-aged mice. Importantly, 10 mg/kg MEL was more efficacious in the treatment of sarcopenia than 5 mg/kg MEL. MEL attenuates sarcopenia in middle-aged mice, and the mechanism may relate to mitochondria-induced oxidative stress and the PGC-1α/TFAM pathway.

Melatonin alleviates arsenic-induced liver injury by regulating protein RKIP and enhancing antioxidant defencse mechanisms.

Arsenic (As) is a highly toxic metal and one of the main factors in cancer development through oxidative stress and production of reactive oxygen species. Prior research has demonstrated melatonin's potential as a free radical scavenger. Raf kinase inhibitory protein (RKIP) is an important regulator of intracellular signaling pathways that has been linked to various types of cancer. The aim of this research was to explore the influence of melatonin's antioxidant properties on the expression of the protein RKIP and the antioxidant status of liver tissue in rats that were exposed to arsenic. Thirty two male Wistar rats were divided into four groups of eight, including control, melatonin-treated (20 mg/Kg of melatonin), sodium arsenite-treated (5.5 mg/Kg of sodium arsenite), and melatonin + sodium arsenite-treated groups (combination) for 4 weeks. The expression level of protein RKIP was measured by Western blot, and malondialdehyde (MDA) content of the liver as well as the activities of antioxidant enzymes were measured. The data analyzed using one-way ANOVA (significance level of p < 0.05) and GraphPad Prism (9) software. Sodium arsenite treatment led to a significant decrease in RKIP protein expression and antioxidant enzyme activity, and an increase in liver MDA levels (p < 0.001). Conversely, melatonin treatment in the combination group resulted in a significant increase in RKIP protein expression and antioxidant enzyme activity and a decrease in liver MDA levels (p < 0.05). These findings suggest that melatonin can attenuate oxidative damage caused by arsenic in liver cells by enhancing RKIP protein expression and antioxidant enzyme activity.

Exploring the association between melatonin and nicotine dependence (Review).

Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction‑related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine‑seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine‑related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug‑induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin‑nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.

Exploring the neuroprotective role of melatonin against nickel-induced neurotoxicity in the left hippocampus.

Previous studies have demonstrated that the hippocampus, a crucial region for memory and cognitive functions, is particularly vulnerable to adverse effects of exposure to heavy metals. Nickel (Ni) is a neurotoxic agent that, primarily induces oxidative stress, a process known to contribute to cellular damage, which consequently affects neurological functions. The antioxidant properties of melatonin are a promising option for preventing the adverse effects of Ni, especially by protecting cells against oxidative stress and related damage. In our investigation of the potential neuroprotective effects of melatonin against Ni-induced neurotoxicity, we chose to administer melatonin through intraperitoneal injection in rats following an intrahippocampal injection of Ni into the left hippocampus. This approach allows us a targeted investigation into the influence of melatonin on the neurotoxic effects of Ni, particularly within the crucial context of the hippocampus. In the present study, we demonstrated that melatonin efficiency reduced lactate dehydrogenase level, and preserved antioxidant enzyme activities in Ni-exposed hippocampal tissue. It also mitigated the decline in superoxide dismutase and catalase activities. On the other hand, melatonin could act directly by reducing reactive oxygen species Ni-induced overproduction. Taking to gather these two potential mechanisms of action could be responsible for the adverse effect of Ni on the behavioral alteration observed in our study. This study provides significant insights into the potential of melatonin to mitigate the detrimental effects of Ni on the brain, particularly into the hippocampal region, suggesting its possible implications for the treatment of neurological disorders related to Ni exposure.

Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies.

This study reviewed the literature on the antioxidant properties of melatonin in rat models. We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses and used the PubMed, LILACS, and Cochrane databases, Google Scholar, and article references, irrespective of publication time. Ten articles involving 485 rats were selected, and the effects of melatonin on antioxidant markers were investigated. Melatonin increased superoxide dismutase in nine studies, glutathione peroxidase in seven studies, and catalase in five studies. In contrast, melatonin reduced glutathione in three studies and malonaldehyde in seven of eight studies. Our findings suggest that melatonin effectively reduces oxidative stress.

Melatonin in Neurodevelopmental Disorders: A Critical Literature Review.

The article presents a review of the relationships between melatonin and neurodevelopmental disorders. First, the antioxidant properties of melatonin and its physiological effects are considered to understand better the role of melatonin in typical and atypical neurodevelopment. Then, several neurodevelopmental disorders occurring during infancy, such as autism spectrum disorder or neurogenetic disorders associated with autism (including Smith-Magenis syndrome, Angelman syndrome, Rett's syndrome, Tuberous sclerosis, or Williams-Beuren syndrome) and neurodevelopmental disorders occurring later in adulthood like bipolar disorder and schizophrenia, are discussed with regard to impaired melatonin production and circadian rhythms, in particular, sleep-wake rhythms. This article addresses the issue of overlapping symptoms that are commonly observed within these different mental conditions and debates the role of abnormal melatonin production and altered circadian rhythms in the pathophysiology and behavioral expression of these neurodevelopmental disorders.

MODELING OF MELATONIN ANTIOXIDANT ACTIVITY IN ASPECT OF CLINICAL APPLICATION IN COVID-19

The most important function of melatonin according to medical clinical trials is antioxidant activity (along with gerontoprotective, anti-stress, immunomodulatory, anti-inflammatory, etc.), which is found everywhere in the human body, as melatonin penetrates all organs and tissues. Therefore, it is important to study the effectiveness of endogenous antioxidants by modelling the mechanism of their interaction with free radicals by quantum chemistry in combination with experimental methods, including electrochemical that enables not only to justify the positive effect of antioxidants, but also to establish the potential significance of these substances as medicines. Electrochemical studies have confirmed the antioxidant properties of melatonin and at the macroscopic level the fundamental difference in the mechanisms of inhibition of antioxidant molecules of hydroxyl radicals and superoxide anion radicals under predominant antioxidant activity with melatonin has been proven. The antioxidant activity of melatonin in the aspect of its clinical application in COVID-19 was supported by comparing the results of quantum chemical studies obtained at the nano-scale (redistribution of electron density, orders of relations between atoms, energy characteristics) with changes in the macroscopic parameters of the process of electroreduction of reactive oxygen species in the presence of melatonin. The potential of applying quantum chemical calculations in combination with electrochemical studies has been demonstrated to substantiate and establish the characteristics and differences of antioxidant activity of melatonin when interacting with a superoxide anion radical and a hydroxyl radical in order to predict ways to create new medicines based on the pharmacological activity of melatonin for its clinical use in COVID-19.

Effect of low concentration of melatonin on the quality of stored red blood cells &lt;em&gt;in vitro&lt;/em&gt;

Introduction. Oxidative stress is one of the important causes of red blood cells (RBCs) storage lesion. As a hormone, melatonin (MT) is also an effective antioxidant, however the pro- and antioxidative properties of MT depend on the cell type, redox state, as well as experimental conditions.Aim of this study — to investigate the protective effects of low concentration of MT on the stored RBCs in vitro.Materials and methods. Leukofi ltered RBCs were incubated in MAP RBC additive solution with or without 150 pg/mL of MT for 42 days under blood bank conditions. The morphology, aggregation index, methemoglobin (MetHb), m alondialdehyde (MDA), glucose, lactic acid and ATP of RBCs were detected on days 0, 7, 14, 21, 28, 35 and 42 to observe the protective effects of MT during the storage of RBCs.Results. During RBCs s torage, the number of deformed RBCs, relative hemolysis rate, aggregation index, MDA and MetHb were signifi cantly affected by both storage time (p &lt; 0.0001) and melatonin (p &lt; 0.01), and they had interaction only on the number of deformed RBCs (p &lt; 0.0001). The concentration of glucose, lactic acid and ATP were affected by storage time (p &lt; 0.0001), but not by MT concentration (p &gt; 0.05). The number of deformed RBCs, relative hemolysis rate, MDA and MetHb in MT group were signifi cantly lower than that in control group at the end of storage stage (p &lt; 0.05).Conclusion. Our study showed low hypnotic drug concentration of MT is speculated to have protective effects on the quality of stored RBCs through antioxidative mechanism.

Effects of melatonin and N-acetylcysteine on aluminum phosphide poisoning in rats.

Aluminum phosphide (ALP) poisoning is one of the deadliest types of poisoning in the world. The antioxidant properties of melatonin and N-acetylcysteine and their effects on reducing cell death have been identified. The aim of this study was to evaluate the effects of N-acetylcysteine and melatonin in the treatment of aluminum phosphide poisoning in rats. Fifty male Wistar rats weighing 200-250 g were tested in five groups of ten. The first group was the control group; the second group received (10 mg/kg) of ALP, the third group received (10 mg/kg) of ALP and (10 mg/kg) of melatonin, the fourth group received (10 mg/kg) of ALP and (10 mg/kg) of N-acetylcysteine, and the last group received (10 mg/kg) of ALP and (10 mg/kg) of melatonin and N-acetylcysteine. The plasma of samples was isolated, and the activity of antioxidant enzymes (glutathione S-transferase (GST), Superoxide dismutase (SOD), and catalase (CAT)) was analyzed. The concentrations of CAT, GST, Glutathione, GSH were decreased in plasma, liver, and kidneys of mice treated with aluminum phosphide; also, the concentrations of aspartate aminotransferase (AST), ALT, and AlK were increased (P < 0.05), while the activity of SOD did not change significantly (P > 0.05). Treatment with N-acetylcysteine and melatonin led to an increase in the activity of CAT, GST, and GSH in plasma, liver, and kidney. After the administration of N-acetylcysteine and melatonin to mice, the levels of all enzymes were close to normal, and the mice survived for 12-15 hours after administration. The administration of N-acetylcysteine (NAC) and melatonin at a dose of 10 mg/kg improves hepatic manifestations and prevents liver necrosis; also, they are considered potential therapeutic agents in the treatment of this poisoning.

Melatonin as a Reducer of Neuro- and Vasculotoxic Oxidative Stress Induced by Homocysteine.

The antioxidant properties of melatonin can be successfully used to reduce the effects of oxidative stress caused by homocysteine. The beneficial actions of melatonin are mainly due to its ability to inhibit the generation of the hydroxyl radical during the oxidation of homocysteine. Melatonin protects endothelial cells, neurons, and glia against the action of oxygen radicals generated by homocysteine and prevents the structural changes in cells that lead to impaired contractility of blood vessels and neuronal degeneration. It can be, therefore, assumed that the results obtained in experiments performed mainly in the in vitro models and occasionally in animal models may clear the way to clinical applications of melatonin in patients with hyperhomocysteinemia, who exhibit a higher risk of developing neurodegenerative diseases (e.g., Parkinson’s disease or Alzheimer’s disease) and cardiovascular diseases of atherothrombotic etiology. However, the results that have been obtained so far are scarce and have seldom been performed on advanced in vivo models. All findings predominately originate from the use of in vitro models and the scarcity of clinical evidence is huge. Thus, this mini-review should be considered as a summary of the outcomes of the initial research in the field concerning the use of melatonin as a possibly efficient attenuator of oxidative stress induced by homocysteine.

The effects of melatonin treatment on oxidative stress induced by ovariohysterectomy in dogs

BackgroundAs one of the most common surgeries performed in veterinary medicine, ovariohysterectomy (OHE) can induce oxidative stress in dogs. The antioxidant properties of melatonin have been confirmed in various studies. This study aimed to investigate the effects of melatonin administration on oxidative stress in dogs before and after OHE. In this study, 25 mature female intact dogs were selected and randomly divided into five equal groups: Melatonin (melatonin, no surgery), OHE (no melatonin, surgery), OHE + melatonin (melatonin, surgery), anesthesia+melatonin (melatonin, sham surgery), and control (no melatonin, no surgery) groups. Melatonin (0.3 mg/Kg/day, p.o.) was administrated to the dogs in the melatonin, OHE + melatonin, and anesthesia+melatonin groups on days − 1, 0, 1, 2, and 3 (day 0 = OHE). Blood sampling was performed on days − 1, 1, 3, and 5 of the study. Blood samples were immediately transferred to the laboratory and sera were separated and stored at − 20 °C. Superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) concentrations were measured with commercial kits.ResultsThe levels of SOD, GPX and CAT were significantly higher in the melatonin and anesthesia+melatonin groups compared to those of the control group at days 3 and 5. The level of antioxidant enzymes significantly decreased in the OHE group compared to that of other groups at days 3 and 5. The administration of melatonin increased the level of antioxidant enzymes in ovariohysterectomized dogs. Ovariohysterectomy significantly increased the concentration of MDA in comparison to that of other groups at day 3. Melatonin administration significantly decreased the level of MDA in melatonin, anesthetized, and ovariohysterectomized dogs at day 3.ConclusionsAdministration of melatonin on day − 1, 0, 1, 2 and 3 modulate the oxidative stress induced by OHE in dogs by increasing antioxidant enzymes concentration and decreasing MDA levels.

Melatonin Prevents the Development of Age-Related Pathology in Male Rats during Accelerated Aging Caused by Impaired Photoperiodism

The purpose of the work was to study the role of melatonin in the development of age-related pathology and morbidity in male rats under model conditions of accelerated aging caused by impaired photoperiodism. Circadian-rhythm disruption upon exposure to light at night initiates the development of age-related changes in the body and contributes to the formation of age-associated diseases. The article presents the results of an experimental study showing that the use of melatonin in laboratory animals in various light regimes (standard lighting, natural lighting in northwest Russia, and constant lighting) significantly reduces the number of cases of intravital morbidity (rhinitis, conjunctivitis, pneumonia, otitis media, etc.) and postmortem-detected, age-related pathology (tumors, chronic diseases of the respiratory and cardiovascular systems, etc.). Apparently, the immunomodulatory and antioxidant properties of melatonin and its participation in the maintenance of energy homeostasis of the body allows this hormone to perform a universal protective mission in the body—to interfere with pathological processes of any origin.

Melatonin and Selenium Suppress Docetaxel-Induced TRPV1 Activation, Neuropathic Pain andOxidativeNeurotoxicity in Mice.

Docetaxel (DT) has been reported to positive therapeutic actions in the treatment of glioblastoma, breast tumors, and prostate cancers. However, it can also induce peripheral neuropathic pain and neurotoxicity as adverse effects. Expression level of TRPV1 cation channel is high in dorsal root ganglion (DRG), and its activation via capsaicin and reactive oxygen species (ROS) mediates peripheral neuropathic pain in mice. As cancer is known to increase the levels of ROS, the protective roles of melatonin (MT) and selenium (Se) were evaluated on the TRPV1-mediated neurotoxicity and pain in the DT-treated mice. Mice and TRPV1 expressing SH-SY5Y cells were equally divided into control, MT, Se, DT, DT+MT, and DT+Se groups. In the results of pain tests in the mice, we observed a decrease in DT-mediated mechanical and heat neuropathic pain by MT and Se. The results of plate reader assay and laser confocal microscopy image analyses indicated a protective role of MT and Se on the DT-induced increase of mitochondrial ROS, cytosolic ROS, apoptosis, lipid peroxidation, intracellular free Zn2+, Ca2+, and caspase-3 and -9 levels in the DRG and SH-SY5Y cells. MT and Se modulated DT-induced decreases of total antioxidant status, reducedglutathione and glutathione peroxidase in the DRG. However, the effects of DT were not observed in the non-TRPV1 expressing SH-SY5Y cells. Hence, MT and Se mediated protective effects against DT-induced adverse peripheral oxidative neurotoxicity and peripheral pain. These effects may be attributed to potent antioxidant properties of MT and Se.

Melatonin and morphine: potential beneficial effects of co-use.

Morphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other side effects including dependence, addiction, respiratory depression, and constipation, which limit its clinical usage. Therefore, identifying the new analgesics with fewer side effects which could increase the effect of morphine and reduce its side effects is crucial. Melatonin, a multifunctional molecule produced in the body, is known to play an important role in pain regulation. The strong anti-inflammatory effect of melatonin is suggested to be involved in the attenuation of the pain associated with inflammation. Melatonin also increases the anti-nociceptive actions of opioids, such as morphine, and reverses their tolerance through regulating several cellular signaling pathways. In this review, published articles evaluating the effect of the co-consumption of melatonin and morphine in different conditions were investigated. Our results show that melatonin has pain-killing properties when administered alone or in combination with other anti-nociceptive drugs. Melatonin decreases morphine consumption in different pathologies. Furthermore, attenuation of morphine intake can be accompanied by reduction of morphine-associated side-effects, including physical dependence, morphine tolerance, and morphine-related hyperalgesia. Therefore, it is reasonable to believe that the combination of melatonin with morphine could reduce morphine-induced tolerance and hyperalgesia, which may result from anti-inflammatory and antioxidant properties of melatonin. Overall, we underscore that, to further ameliorate patients' life quality and control their pain in various pathological conditions, melatonin deserves to be used with morphine by anesthesiologists in clinical practice.

Radiological Pharmacology Drugs: Therapeutic Potential of Melatonin

The purpose of the article is to draw attention to Melatonin as a means of radiological pharmacology within the framework of drugs’ reprofiling [13] and the “off-label” strategy (application for medical purposes does not correspond to the instructions for the basic medical use of the drug). Melatonin has, to varying degrees, a dose-dependent antistressor, sedative, hypnogenic, neuroprotective, geroprotective (a general consistent pattern for all geroprotectors – earlier initiation of drug use provides a greater effect), antidepressant, antioxidant, antitumor, antiapoptotic (in normal cells), proapoptotic (in cancer cells), oncostatic, antimetastatic, immunomodulatory, radioprotective, radiosensitizing, anti-infectious, analgesic, hepatoprotective geroprotective, antihypertensive, anti-inflammatory, moderate contraceptive (for women) action. Melatonin regulates neuroendocrine functions, respiratory rate, reproductive function, osteogenic differentiation of mesenchymal stem cells, formation and protection of bones; modulates the activity of bone-forming osteoblasts and bone-resorbing osteoclasts; reduces pain sensitivity; affects the intracellular calcium content. The antioxidant properties of Melatonin are closely related to its antitumor effect. Studies have demonstrated that melatonin has a self-sufficient oncostatic effect in cancer of the breast, ovaries, endometrium, pancreas, prostate, lungs; melanoma, hepatocellular carcinoma, colorectal cancer, glioblastoma, and leiomyosarcoma. Key words: pineal gland, melatonin, radioprotector, radiological pharmacology.

Association Between Antiarrhythmic, Electrophysiological, and Antioxidative Effects of Melatonin in Ischemia/Reperfusion.

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and “ischemic” conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) (p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT (p = 0.001), whereas VT/VF incidence was associated with baseline ATs (p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation (p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.

On the benefit of melatonin in protection against ouabain-induced arrhythmia through modulation of oxidative stress factors in isolated rat atria

ABSTRACTConsidering the cardioprotective and antioxidant properties of melatonin, in the present experiment, we investigated the possible involvement of oxidative stress factors in antiarrhythmic effects of melatonin in ouabain-induced arrhythmia in isolated rat atria. Male rats were divided into two groups, receiving either of melatonin (2 mg/kg) or vehicle, orally once daily for three weeks. Rats were anesthetized, and atria were isolated and incubated with ouabain in an organ bath. Time of onset of arrhythmia and asystole as well as atrial beating rate and contractile force were recorded. We also measured the activity of superoxide dismutase (SOD) and levels of thiobarbituric acid reactive substances (TBARS) in atria after injection of ouabain to animals. Pretreatment of animals with melatonin could significantly postpone the onset of arrhythmia and asystole compared with vehicle-treated group (P ≤ 0.001). Incubation of ouabain boosted the atrial beating rate in vehicle-treated group (P ≤ 0.01), while this response in melatonin-treated group was not significant (P > 0.05). Injection of ouabain decreased the activity of SOD and increased the levels of TBARS in atria (P ≤ 0.001, P ≤ 0.01, respectively), while pretreatment of animals with melatonin reversed these effects (P ≤ 0.05). It is concluded that melatonin possesses antiarrhythmic properties, and oxidative stress factors might mediate this response.

The benefit of a supplement with the antioxidant melatonin on redox status and muscle damage in resistance-trained athletes.

Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg·day-1 of melatonin or placebo 30 min before bedtime during 4 weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG·GSH-1 and GPx·GRd-1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells

Background/Aims: Melatonin is a hormone transferring information about duration of darkness to the organism and is known to modulate several signaling pathways in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status of the cells, etc. Melatonin has been shown to exert antiproliferative and cytotoxic effects on various human cancers. We proposed that this hormone can differently affect tumour cells and healthy cells. Methods: We compared the effect of 24 h melatonin treatment on calcium transport (by fluorescent probes FLUO-3AM and Rhod-5N), ER stress (determined as changes in the expression of CHOP, XBP1 and fluorescently, using Thioflavin T), ROS formation (by CellROX® Green/Orange Reagent) and apoptosis induction (by Annexin-V-FLUOS/propidiumiodide) in two tumour cell lines – ovarian cancer cell line A2780 and stable cell line DLD1 derived from colorectal carcinoma, with non-tumour endothelial cell line EA.hy926. Results: Melatonin increased apoptosis in both tumour cell lines more than twice, while in EA.hy926 cells the apoptosis was increased only by 30%. As determined by silencing with appropriate siRNAs, both, type 1 sodium/calcium exchanger and type 1 IP₃ receptor are involved in the apoptosis induction. Antioxidant properties of melatonin were significantly increased in EA.hy926 cells, while in tumour cell lines this effect was much weaker. Conclusion: Taken together, melatonin has different antioxidative effects on tumour cells compared to non-tumour ones; it also differs in the ability to induce apoptosis through the type 1 sodium/calcium exchanger, and type 1 IP₃ receptor. Different targeting of calcium transport systems in tumour and normal, non-tumour cells is suggested as a key mechanism how melatonin can exert its anticancer effects. Therefore, it might have a potential as a novel therapeutic implication in cancer treatment.