Antioxidants

Editorial

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6 pages, 220 KiB

Open AccessEditorial

Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions

by Maria Bantounou, Josip Plascevic and Helen F. Galley

Antioxidants 2022, 11(3), 532; https://doi.org/10.3390/antiox11030532 - 10 Mar 2022

Cited by 38 | Viewed by 4101

Abstract

Melatonin, an indoleamine derived from tryptophan and produced in the pineal gland and other tissues [...] Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

Research

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17 pages, 2965 KiB

Open AccessArticle

Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

by Alejandro Gonzaléz-Candia, Pamela V. Arias, Simón A. Aguilar, Esteban G. Figueroa, Roberto V. Reyes, Germán Ebensperger, Aníbal J. Llanos and Emilio A. Herrera

Antioxidants 2021, 10(11), 1658; https://doi.org/10.3390/antiox10111658 - 22 Oct 2021

Cited by 18 | Viewed by 3658

Abstract

Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 [...] Read more.

Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg⁻¹·d⁻¹) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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18 pages, 5452 KiB

Open AccessArticle

Crosstalk between Peroxisomal Activities and Nrf2 Signaling in Porcine Embryos

by Eui-Hyun Kim, Muhammad-Rosyid Ridlo, Byeong-Chun Lee and Geon A. Kim

Antioxidants 2021, 10(5), 771; https://doi.org/10.3390/antiox10050771 - 13 May 2021

Cited by 8 | Viewed by 2467

Abstract

Melatonin and phytanic acid (PA) are known to be involved in lipid metabolism and β-oxidation, in which peroxisomal activities also significantly participate. In addition, other studies have reported that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway mediates lipid metabolism and [...] Read more.

Melatonin and phytanic acid (PA) are known to be involved in lipid metabolism and β-oxidation, in which peroxisomal activities also significantly participate. In addition, other studies have reported that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway mediates lipid metabolism and its subsequent cascades. As these mechanisms are partially involved in porcine oocytes or embryonic development, we hypothesized that the factors governing these mechanisms could be interconnected. Therefore, we aimed to investigate possible crosstalk between peroxisomal activities and Nrf2 signaling in porcine embryos following melatonin and PA treatment. Porcine embryos were cultured for seven days after parthenogenetic activation, and subsequently treated with melatonin and PA, or injected with Pex19-targeted siRNAs. Real-time PCR, immunocytochemistry, and BODIPY staining were used to evaluate peroxisomal activities, Nrf2 signaling, and subsequent lipid metabolism. We found that melatonin/PA treatment enhanced embryonic development, whereas injection with Pex19-targeted siRNAs had the opposite effect. Moreover, melatonin/PA treatment upregulated peroxisomal activities, Nrf2 signaling, lipid metabolism, and mitochondrial membrane potentials, whereas most of these mechanisms were downregulated by Pex19-targeted siRNAs. Therefore, we suggest that there is a connection between the action of melatonin and PA and the Nrf2 signaling pathway and peroxisomal activities, which positively influences porcine embryonic development. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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20 pages, 3928 KiB

Open AccessArticle

Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

by Ana Guerra-Librero, Beatriz I. Fernandez-Gil, Javier Florido, Laura Martinez-Ruiz, César Rodríguez-Santana, Ying-Qiang Shen, José M. García-Verdugo, Alba López-Rodríguez, Iryna Rusanova, Alfredo Quiñones-Hinojosa, Darío Acuña-Castroviejo, Jordi Marruecos, Tomás De Haro and Germaine Escames

Antioxidants 2021, 10(4), 603; https://doi.org/10.3390/antiox10040603 - 14 Apr 2021

Cited by 27 | Viewed by 6302

Abstract

Metabolic reprogramming, which is characteristic of cancer cells that rapidly adapt to the hypoxic microenvironment and is crucial for tumor growth and metastasis, is recognized as one of the major mechanisms underlying therapeutic resistance. Mitochondria, which are directly involved in metabolic reprogramming, are [...] Read more.

Metabolic reprogramming, which is characteristic of cancer cells that rapidly adapt to the hypoxic microenvironment and is crucial for tumor growth and metastasis, is recognized as one of the major mechanisms underlying therapeutic resistance. Mitochondria, which are directly involved in metabolic reprogramming, are used to design novel mitochondria-targeted anticancer agents. Despite being targeted by melatonin, the functional role of mitochondria in melatonin’s oncostatic activity remains unclear. In this study, we aim to investigate the role of melatonin in mitochondrial metabolism and its functional consequences in head and neck cancer. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 100, 500, and 1500 µM of melatonin for 1, 3, and 5 days, and found a connection between a change of metabolism following melatonin treatment and its effects on mitochondria. Our results demonstrate that melatonin induces a shift to an aerobic mitochondrial metabolism that is associated with changes in mitochondrial morphology, function, fusion, and fission in HNSCC. We found that melatonin increases oxidative phosphorylation (OXPHOS) and inhibits glycolysis in HNSCC, resulting in increased ROS production, apoptosis, and mitophagy, and decreased cell proliferation. Our findings highlight new molecular pathways involved in melatonin’s oncostatic activity, suggesting that it could act as an adjuvant agent in a potential therapy for cancer patients. We also found that high doses of melatonin, such as those used in this study for its cytotoxic impact on HNSCC cells, might lead to additional effects through melatonin receptors. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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22 pages, 4634 KiB

Open AccessArticle

Melatonin Modulates the Antioxidant Defenses and the Expression of Proinflammatory Mediators in Pancreatic Stellate Cells Subjected to Hypoxia

by Matias Estaras, Manuel R. Gonzalez-Portillo, Remigio Martinez, Alfredo Garcia, Mario Estevez, Miguel Fernandez-Bermejo, Jose M. Mateos, Daniel Vara, Gerardo Blanco-Fernández, Diego Lopez-Guerra, Vicente Roncero, Gines M. Salido and Antonio Gonzalez

Antioxidants 2021, 10(4), 577; https://doi.org/10.3390/antiox10040577 - 8 Apr 2021

Cited by 9 | Viewed by 3852

Abstract

Pancreatic stellate cells (PSC) play a major role in the formation of fibrotic tissue in pancreatic tumors. On its side, melatonin is a putative therapeutic agent for pancreatic cancer and inflammation. In this work, the actions of melatonin on PSC subjected to hypoxia [...] Read more.

Pancreatic stellate cells (PSC) play a major role in the formation of fibrotic tissue in pancreatic tumors. On its side, melatonin is a putative therapeutic agent for pancreatic cancer and inflammation. In this work, the actions of melatonin on PSC subjected to hypoxia were evaluated. Reactive oxygen species (ROS) generation reduced (GSH) and oxidized (GSSG) levels of glutathione, and protein and lipid oxidation were analyzed. The phosphorylation of nuclear factor erythroid 2-related factor (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and the regulatory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα) was studied. The expression of Nrf2-regulated antioxidant enzymes, superoxide dismutase (SOD) enzymes, cyclooxygenase 2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also studied. Total antioxidant capacity (TAC) was assayed. Finally, cell viability was studied. Under hypoxia and in the presence of melatonin generation of ROS was observed. No increases in the oxidation of proteins or lipids were detected. The phosphorylation of Nrf2 and the expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1, heme oxygenase-1, SOD1, and of SOD2 were augmented. The TAC was increased. Protein kinase C was involved in the effects of melatonin. Melatonin decreased the GSH/GSSG ratio at the highest concentration tested. Cell viability dropped in the presence of melatonin. Finally, melatonin diminished the phosphorylation of NF-kB and the expression of COX-2, IL-6, and TNF-α. Our results indicate that melatonin, at pharmacological concentrations, modulates the red-ox state, viability, and the expression of proinflammatory mediators in PSC subjected to hypoxia. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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19 pages, 3652 KiB

Open AccessArticle

The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle

by Ramy KA Sayed, Marisol Fernández-Ortiz, José Fernández-Martínez, Paula Aranda Martínez, Ana Guerra-Librero, César Rodríguez-Santana, Tomás de Haro, Germaine Escames, Darío Acuña-Castroviejo and Iryna Rusanova

Antioxidants 2021, 10(4), 524; https://doi.org/10.3390/antiox10040524 - 27 Mar 2021

Cited by 19 | Viewed by 3960

Abstract

Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) [...] Read more.

Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3⁻) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (p < 0.01), miR-146a, and miR-223 (p < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (p < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3⁻ mice (p < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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15 pages, 3321 KiB

Open AccessArticle

Melatonin Regulates Chloroplast Protein Quality Control via a Mitogen-Activated Protein Kinase Signaling Pathway

by Hyoung Yool Lee and Kyoungwhan Back

Antioxidants 2021, 10(4), 511; https://doi.org/10.3390/antiox10040511 - 25 Mar 2021

Cited by 36 | Viewed by 3565

Abstract

Serotonin N-acetyltransferase 1 (SNAT1), the penultimate enzyme for melatonin biosynthesis has shown N-acetyltransferase activity toward multiple substrates, including histones, serotonin, and plastid proteins. Under two different light conditions such as 50 or 100 μmol m⁻² s⁻¹, a SNAT1 [...] Read more.

Serotonin N-acetyltransferase 1 (SNAT1), the penultimate enzyme for melatonin biosynthesis has shown N-acetyltransferase activity toward multiple substrates, including histones, serotonin, and plastid proteins. Under two different light conditions such as 50 or 100 μmol m⁻² s⁻¹, a SNAT1-knockout (snat1) mutant of Arabidopsis thaliana ecotype Columbia (Col-0) exhibited small size phenotypes relative over wild-type (WT) Arabidopsis Col-0. Of note, the small phenotype is stronger when growing at the 50 μmol m⁻² s⁻¹, exhibiting a dwarfism phenotype and delayed flowering. The snat1 Arabidopsis Col-0 accumulated less starch than the WT Col-0. Moreover, snat1 exhibited lower Lhcb1, Lhcb4, and RBCL protein levels, compared with the WT Col-0, but no changes in the corresponding transcripts, suggesting the involvement of melatonin in chloroplast protein quality control (CPQC). Accordingly, caseinolytic protease (Clp) and chloroplast heat shock proteins (CpHSPs), two key proteins involved in CPQC, as well as ROS defense were suppressed in snat1. In contrast, exogenous melatonin treatment induced expression of Clp, CpHSP, APX1, and GST, but not other growth-related genes such as DWF4, KS, and IAA1. Finally, the induction of ClpR1, APX1, and GST1 in response to melatonin was inhibited in the mitogen-activated protein kinase (MAPK) knockdown Arabidopsis (mpk3/6), suggesting that melatonin-mediated CPQC was mediated, in part, by the MAPK signaling cascade. These results suggest that melatonin is involved in CPQC, which plays a pivotal role in starch synthesis in plants. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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18 pages, 2533 KiB

Open AccessArticle

Melatonin Reduces NLRP3 Inflammasome Activation by Increasing α7 nAChR-Mediated Autophagic Flux

by Víctor Farré-Alins, Paloma Narros-Fernández, Alejandra Palomino-Antolín, Céline Decouty-Pérez, Ana Belen Lopez-Rodriguez, Esther Parada, Alicia Muñoz-Montero, Vanessa Gómez-Rangel, Francisco López-Muñoz, Eva Ramos, Águeda González-Rodríguez, Luis Gandía, Alejandro Romero and Javier Egea

Antioxidants 2020, 9(12), 1299; https://doi.org/10.3390/antiox9121299 - 18 Dec 2020

Cited by 36 | Viewed by 4436

Abstract

Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of [...] Read more.

Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of melatonin on the regulation of the NLRP3 inflammasome through α7 nicotinic receptor (nAChR) and its relationship with autophagy. For this purpose, we have used pharmacological and genetic approaches in lipopolysaccharide (LPS)-induced inflammation models in both in vitro and in vivo models. In the BV2 cell line, LPS inhibited autophagy, which increased NLRP3 protein levels. However, melatonin promoted an increase in the autophagic flux. Treatment of glial cultures from wild-type (WT) mice with LPS followed by extracellular adenosine triphosphate (ATP) produced the release of IL-1β, which was reversed by melatonin pretreatment. In cultures from α7 nAChR knock-out (KO) mice, melatonin did not reduce IL-1β release. Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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17 pages, 4641 KiB

Open AccessArticle

Melatonin Ameliorates Inflammation and Oxidative Stress by Suppressing the p38MAPK Signaling Pathway in LPS-Induced Sheep Orchitis

by Shou-Long Deng, Bao-Lu Zhang, Russel J. Reiter and Yi-Xun Liu

Antioxidants 2020, 9(12), 1277; https://doi.org/10.3390/antiox9121277 - 14 Dec 2020

Cited by 37 | Viewed by 3918

Abstract

Gram-negative bacterial infections of the testis can lead to infectious orchitis, which negatively influences steroid hormone synthesis and spermatogenesis. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall, acts via toll like receptors 4 (TLR4) to trigger innate immune responses and [...] Read more.

Gram-negative bacterial infections of the testis can lead to infectious orchitis, which negatively influences steroid hormone synthesis and spermatogenesis. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall, acts via toll like receptors 4 (TLR4) to trigger innate immune responses and activate nuclear factor kappa B signaling. The protective mechanisms of melatonin on LPS-induced infectious orchitis have not been reported. Herein, we developed an LPS-induced sheep infectious orchitis model. In this model, the phagocytic activity of testicular macrophages (TM) was enhanced after melatonin treatment. Moreover, we found that melatonin suppressed secretion of TM pro-inflammatory factors by suppressing the p38MAPK pathway and promoting Leydig cell testosterone secretion. Expressions of GTP cyclohydrolase-I and NADPH oxidase-2 were reduced by melatonin while heme oxygenase-1 expression was up-regulated. Thus, melatonin reduced the severity of LPS-induced orchitis by stimulating antioxidant activity. The results of this study provide a reference for the treatment of acute infectious orchitis. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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Review

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29 pages, 496 KiB

Open AccessReview

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

by Eva Ramos, Francisco López-Muñoz, Emilio Gil-Martín, Javier Egea, Iris Álvarez-Merz, Sakshi Painuli, Prabhakar Semwal, Natália Martins, Jesús M. Hernández-Guijo and Alejandro Romero

Antioxidants 2021, 10(7), 1152; https://doi.org/10.3390/antiox10071152 - 20 Jul 2021

Cited by 22 | Viewed by 8299

Abstract

Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune [...] Read more.

Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

16 pages, 590 KiB

Open AccessReview

The Role of Melatonin on NLRP3 Inflammasome Activation in Diseases

by Burak Ibrahim Arioz, Emre Tarakcioglu, Melis Olcum and Sermin Genc

Antioxidants 2021, 10(7), 1020; https://doi.org/10.3390/antiox10071020 - 24 Jun 2021

Cited by 34 | Viewed by 5458

Abstract

NLRP3 inflammasome is a part of the innate immune system and responsible for the rapid identification and eradication of pathogenic microbes, metabolic stress products, reactive oxygen species, and other exogenous agents. NLRP3 inflammasome is overactivated in several neurodegenerative, cardiac, pulmonary, and metabolic diseases. [...] Read more.

NLRP3 inflammasome is a part of the innate immune system and responsible for the rapid identification and eradication of pathogenic microbes, metabolic stress products, reactive oxygen species, and other exogenous agents. NLRP3 inflammasome is overactivated in several neurodegenerative, cardiac, pulmonary, and metabolic diseases. Therefore, suppression of inflammasome activation is of utmost clinical importance. Melatonin is a ubiquitous hormone mainly produced in the pineal gland with circadian rhythm regulatory, antioxidant, and immunomodulatory functions. Melatonin is a natural product and safer than most chemicals to use for medicinal purposes. Many in vitro and in vivo studies have proved that melatonin alleviates NLRP3 inflammasome activity via various intracellular signaling pathways. In this review, the effect of melatonin on the NLRP3 inflammasome in the context of diseases will be discussed. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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27 pages, 2036 KiB

Open AccessReview

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

by Paula Fernández-Palanca, Carolina Méndez-Blanco, Flavia Fondevila, María J. Tuñón, Russel J. Reiter, José L. Mauriz and Javier González-Gallego

Antioxidants 2021, 10(1), 103; https://doi.org/10.3390/antiox10010103 - 12 Jan 2021

Cited by 37 | Viewed by 6099

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with antioxidant, chronobiotic and anti-inflammatory properties; reduced levels of this hormone are associated with higher risk of cancer. Several beneficial effects of melatonin have been described in a broad number of tumors, including liver cancers. In [...] Read more.

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with antioxidant, chronobiotic and anti-inflammatory properties; reduced levels of this hormone are associated with higher risk of cancer. Several beneficial effects of melatonin have been described in a broad number of tumors, including liver cancers. In this work we systematically reviewed the publications of the last 15 years that assessed the underlying mechanisms of melatonin activities against liver cancers, and its role as coadjuvant in the treatment of these tumors. Literature research was performed employing PubMed, Scopus and Web of Science (WOS) databases and, after screening, 51 articles were included. Results from the selected studies denoted the useful actions of melatonin in preventing carcinogenesis and as a promising treatment option for the primary liver tumors hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), either alone or in combination with other compounds. Different processes were modulated by the indole, such as inhibition of oxidative stress, proliferation, angiogenesis and invasion, promotion of immune system response, cell cycle arrest and apoptosis, as well as recovery of circadian rhythms and autophagy modulation. Taken together, the present systematic review highlights the evidence that document the potential role of melatonin in improving the landscape of liver tumor treatment. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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31 pages, 353 KiB

Open AccessReview

Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection

by Prapimpun Wongchitrat, Mayuri Shukla, Ramaswamy Sharma, Piyarat Govitrapong and Russel J. Reiter

Antioxidants 2021, 10(1), 47; https://doi.org/10.3390/antiox10010047 - 2 Jan 2021

Cited by 28 | Viewed by 10828

Abstract

Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and [...] Read more.

Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common. Recently, extensive research-based studies have revealed and acknowledged the clinical and preventive roles of melatonin in some viral diseases. Melatonin has been shown to have antiviral properties against several viral infections which are accompanied by neurological symptoms. The beneficial properties of melatonin relate to its properties as a potent antioxidant, anti-inflammatory, and immunoregulatory molecule and its neuroprotective effects. In this review, what is known about the therapeutic role of melatonin in virus-induced neuropathogenesis is summarized and discussed. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

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