Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

Reíter, Russel J.; Sharma, Ramaswamy; Rosales-Corral, Sergio; Coto‐Montes, Ana; Boga, José Antonio; Vriend, Jerry

doi:10.1007/978-3-030-32857-3_14

Cited by 3 publications

(2 citation statements)

References 279 publications

(304 reference statements)

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“…In recent decades, a number of systemic functions of melatonin have been established, largely determining the vital functions of the body. These aspects of melatonin are usually well known [25].…”

Section: Results and Their Discussionmentioning

confidence: 99%

Ultrastructural Changes of the Pineal Gland in Epilepsy

Litovchenko,

Dubenko,

Sazonov

et al. 2023

PEP

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Circadian mechanisms modulate neuronal excitability at several levels, and their destruction can cause excessive uncontrolled excitability. Previous studies have shown that epilepsy is associated with melatonin levels. Melatonin is a powerful chronobiotic secreted from the pineal gland; helps to maintain normal circadian rhythms and is used to treat some neurological and psychiatric disorders. Circadian rhythms and sleep/wake mechanisms play role in the epilepsy. Melatonin deficiency can decrease seizure threshold, and hence could increase seizure activity. The aim of the study was to identify ultrastructural changes in the pineal gland in an experimental model of epilepsy. Materials and methods. The experiment was carried out on Wistar rats, 5-6 months of age, weight of about 200 g, 36 experimental and 10 control animals. Electrically provoked experimental epileptic seizures model in rats was reproduced. The rats developed spontaneous generalized seizures after 9-14 stimulations. Material for histological examinations was taken after stable formation (for >1 month) of repeated seizures. Ultrathin sections, after contrast with Reynolds lead citrate, were studied under an electron microscope at an accelerating voltage of 75 kV. The increase was selected adequate to the study and ranged from 20,000 to 60,000 times. Results. Experimental studies have confirmed the presence of stable dystrophic, up to apoptosis of some cells, morphological changes of the pineal gland in the experimental model of epilepsy in rats, which is the reason for the decrease in its functional activity. Conclusions. Our experimental data on the morphological changes of the pineal gland confirm the conclusion about a stable, possibly irreversible, decrease in gland function in epilepsy due to damage and disruption of the structure of its cells. Given the polyfunctionality of melatonin, its deficiency can be one of the causes of changes in neural networks, impaired permeability of synaptic membranes, and as a consequence, increased epileptic activity of neurons.

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Section: Results and Their Discussionmentioning

confidence: 99%

Ultrastructural Changes of the Pineal Gland in Epilepsy

Litovchenko,

Dubenko,

Sazonov

et al. 2023

PEP

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“…In human hexokinase 2 (HK2) cells, an immortalized proximal tubule epithelial cell line, melatonin was found to counteract the lethal effects of cisplatin, by inducing its anti-apoptotic actions. The intermediate events in this process were observed to be mediated through the regulation of expression BAX/Bcl-2 ratio and disruption of mitochondrial membrane potential 31 . Additionally, Shen et al supposed that pathways other than those associated with apoptosis or necrosis inhibited the proliferation of ovarian cancer cell lines (OVCAR-429 and PA-1), as they indicated non-significant increases in the percentage of cells undergoing necrosis, apoptosis or caspase 3 activation after 4 h of melatonin treatment at 400 to 800 μM 28 .…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative effect of melatonin in human hepatoma HepG2 cells occurs mainly through cell cycle arrest and inflammation inhibition

Nabih

Hamed

Yahya

2023

Sci Rep

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Hepatocellular carcinoma (HCC) is the major lethal primary liver malignant worldwide. Although, melatonin has various antitumor bioactivities; there is a requirement for more investigations to elucidate the not discussed effects, and the controversial responses of the treatment with melatonin on targets mediated in HCC. To achieve the aim of the present study, HCC-HepG2 cells were treated with different concentrations of melatonin at various time intervals. The selected minimal proliferation inhibition doses of melatonin were then incubated with cells to examine the arresting effect of melatonin on dividing cells using flow cytometry. Furthermore, the molecular patterns of genes that contributed to apoptosis, drug resistance development, antioxidation, and melatonin crossing were quantified by qRT-PCR. Additionally, the Human inflammation antibody array membrane (40 targets) was used to check the anti-inflammatory effect of melatonin. Our results validated that, melatonin shows anti-proliferative action through preserving cells in G0/G1 phase (P < 0.001) that is associated with a highly significant increase in the expression level of the P53 gene (P < 0.01). On contrary, as a novelty, our data recorded decreases in expression levels of genes involved in the pro-apoptotic pathway; with a significant increase (P < 0.05) in the expression level of an anti-apoptotic gene, Bcl2. Interestingly, we detected observed increases in the expression levels of genes responsible for conferring drug resistance including ABCB1, ABCC1, and ABCC5. Our study proved the anti-inflammatory activity of 1 mM melatonin in HCC-HepG2 cells. Accordingly, we can conclude that melatonin facilitates the anti-proliferation of cells at doses of 1 mM, and 2.5 mM after 24 h. This action is initiated through cell cycle arrest at G0/G1 phase via increasing the expression of P53, but independently on apoptosis. Collectively, melatonin is an effective anti-inflammatory and anti-proliferative promising therapy for the treatment of HCC. However, its consumption should be cautious to avoid the development of drug resistance and provide a better treatment strategy.

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Melatonin Alleviates High Glucose-induced Oxidative Stress and Mitochondrial Dysfunction in Chondrocytes

Mehrzadi,

Hassani,

Hosseinzadeh

2024

CDTH

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Background:: Hyperglycemia triggers mitochondrial dysfunction in chondrocytes, potentially contributing to cell damage and the onset of osteoarthritis. Objective:: This study is undertaken with the objective of examining the protective properties of melatonin against toxicity induced by high glucose in C28I2 human chondrocytes. Methods:: To determine non-cytotoxic concentrations of melatonin, various concentrations (10, 25, 50, 75, 100, 500, and 1000 μM) were assessed over different time periods (24, 48, and 72 hours) for their impact on C28I2 cell viability. Following this, cells underwent a pretreatment with melatonin (10 and 100 μM) for 6 hours. This was followed by subjecting the cells to a high concentration of glucose (75 mM) for 48 hours. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), alongside the enzymatic activities of glutathione peroxidase, superoxide dismutase, and catalase were quantitatively assessed. To assess mitochondrial function, we evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio and measured the mitochondrial membrane potential (MMP). Results:: Elevated glucose levels significantly increased ROS and MDA levels, accompanied by reduced MMP, an elevated ADP/ATP ratio, and altered antioxidant enzyme activity. Pretreatment with melatonin effectively reversed the mitochondrial toxicity induced by high glucose (75 mM). Conclusion:: These results indicate that melatonin exhibits a protective influence against hyperglycemia- induced toxicity in chondrocyte mitochondria.

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Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

Cited by 3 publications

References 279 publications

Ultrastructural Changes of the Pineal Gland in Epilepsy

Ultrastructural Changes of the Pineal Gland in Epilepsy

Anti-proliferative effect of melatonin in human hepatoma HepG2 cells occurs mainly through cell cycle arrest and inflammation inhibition

Melatonin Alleviates High Glucose-induced Oxidative Stress and Mitochondrial Dysfunction in Chondrocytes

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