Antioxidants

Editorial

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4 pages, 205 KiB

Open AccessEditorial

How We Can Change Clinical Practice Using Antioxidant Molecules?

by Gaia Favero and Rita Rezzani

Antioxidants 2022, 11(6), 1116; https://doi.org/10.3390/antiox11061116 - 4 Jun 2022

Viewed by 1486

Abstract

The collection of studies in this Special Issue, “The Role of Antioxidant Molecules and Melatonin in Cellular Protection”, published in Antioxidants (accessed on 30 April 2021; https://www [...] Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

Research

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16 pages, 3767 KiB

Open AccessArticle

Combined Melatonin and Extracorporeal Shock Wave Therapy Enhances Podocyte Protection and Ameliorates Kidney Function in a Diabetic Nephropathy Rat Model

by Chang-Chun Hsiao, You-Syuan Hou, Yu-Hsuan Liu, Jih-Yang Ko and Chien-Te Lee

Antioxidants 2021, 10(5), 733; https://doi.org/10.3390/antiox10050733 - 6 May 2021

Cited by 4 | Viewed by 2631

Abstract

(1) Background: Diabetic nephropathy (DN) is common complication of diabetes. Current therapy for DN does not include promotion of podocyte protection. Therefore, we investigated the therapeutic effect of melatonin (Mel) combined extracorporeal shock wave (SW) therapy on a DN rat model. (2) Methods: [...] Read more.

(1) Background: Diabetic nephropathy (DN) is common complication of diabetes. Current therapy for DN does not include promotion of podocyte protection. Therefore, we investigated the therapeutic effect of melatonin (Mel) combined extracorporeal shock wave (SW) therapy on a DN rat model. (2) Methods: The DN rats were treated with Mel (5 mg/kg) twice a week for 6 weeks and SW treatment once a week (0.13 mJ/mm²) for 6 weeks. We assessed urine microalbumin, albumin to creatinine ratio (ACR), glomerular hypertrophy, glomerular fibrosis, podocyte markers (Wilm’s tumor protein-1, synaptopodin and nephrin), cell proliferation, cell survival, cell apoptosis, renal inflammation and renal oxidative stress. (3) Results: The Mel combined SW therapy regimen significantly reduced urine microalbumin excretion (3.3 ± 0.5 mg/dL, p < 0.001), ACR (65.2 ± 8.3 mg/g, p < 0.001), glomerular hypertrophy (3.1 ± 0.1 × 10⁶ μm³, p < 0.01) and glomerular fibrosis (0.9 ± 0.4 relative mRNA fold, p < 0.05). Moreover, the Mel combined SW therapy regimen significantly increased podocyte number (44.1 ± 5.0% area of synaptopodin, p < 0.001) in the Mel combined SW group. This is likely primarily because Mel combined with SW therapy significantly reduced renal inflammation (753 ± 46 pg/mg, p < 0.01), renal oxidative stress (0.6 ± 0.04 relative density, p < 0.05), and apoptosis (0.3 ± 0.03 relative density, p < 0.001), and also significantly increased cell proliferation (2.0 ± 0.2% area proliferating cell nuclear antigen (PCNA), p < 0.01), cell survival, and nephrin level (4.2 ± 0.4 ng/mL, p < 0.001). (4) Conclusions: Mel combined SW therapy enhances podocyte protection and ameliorates kidney function in a DN rat model. Mel combined SW therapy may serve as a novel noninvasive and effective treatment of DN. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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24 pages, 7984 KiB

Open AccessArticle

Melatonin Mitigates the Infection of Colletotrichum gloeosporioides via Modulation of the Chitinase Gene and Antioxidant Activity in Capsicum annuum L.

by Muhammad Ali, Anthony Tumbeh Lamin-Samu, Izhar Muhammad, Mohamed Farghal, Abdul Mateen Khattak, Ibadullah Jan, Saeed ul Haq, Abid Khan, Zhen-Hui Gong and Gang Lu

Antioxidants 2021, 10(1), 7; https://doi.org/10.3390/antiox10010007 - 23 Dec 2020

Cited by 27 | Viewed by 4734

Abstract

Anthracnose, caused by Colletotrichum gloeosporioides, is one of the most damaging pepper (Capsicum annum L.) disease. Melatonin induces transcription of defense-related genes that enhance resistance to pathogens and mediate physiological activities in plants. To study whether the melatonin-mediated pathogen resistance is [...] Read more.

Anthracnose, caused by Colletotrichum gloeosporioides, is one of the most damaging pepper (Capsicum annum L.) disease. Melatonin induces transcription of defense-related genes that enhance resistance to pathogens and mediate physiological activities in plants. To study whether the melatonin-mediated pathogen resistance is associated with chitinase gene (CaChiIII2), pepper plants and Arabidopsis seeds were treated with melatonin, then CaChiIII2 activation, hydrogen peroxide (H₂O₂) levels, and antioxidant enzymes activity during plant–pathogen interactions were investigated. Melatonin pretreatment uncoupled the knockdown of CaChiIII2 and transiently activated its expression level in both control and CaChiIII2-silenced pepper plants and enhanced plant resistance. Suppression of CaChiIII2 in pepper plants showed a significant decreased in the induction of defense-related genes and resistance to pathogens compared with control plants. Moreover, melatonin efficiently enabled plants to maintain intracellular H₂O₂ concentrations at steady-state levels and enhanced the activities of antioxidant enzymes, which possibly improved disease resistance. The activation of the chitinase gene CaChiIII2 in transgenic Arabidopsis lines was elevated under C. gloeosporioides infection and exhibited resistance through decreasing H₂O₂ biosynthesis and maintaining H₂O₂ at a steady-state level. Whereas melatonin primed CaChiIII2-overexpressed (OE) and wild-type (WT) Arabidopsis seedlings displayed a remarkable increase in root-length compared to the unprimed WT plants. Using an array of CaChiIII2 knockdown and OE, we found that melatonin efficiently induced CaChiIII2 and other pathogenesis-related genes expressions, responsible for the innate immunity response of pepper against anthracnose disease. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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14 pages, 1920 KiB

Open AccessArticle

Melatonin Can Modulate the Effect of Navitoclax (ABT-737) in HL-60 Cells

by Alexey Lomovsky, Yulia Baburina, Irina Odinokova, Margarita Kobyakova, Yana Evstratova, Linda Sotnikova, Roman Krestinin and Olga Krestinina

Antioxidants 2020, 9(11), 1143; https://doi.org/10.3390/antiox9111143 - 18 Nov 2020

Cited by 17 | Viewed by 2981

Abstract

Melatonin (N-acetyl-5-methoxytryptamine MEL) is an indolamine that has antioxidant, anti-inflammatory and anti-tumor properties. Moreover, MEL is capable of exhibiting both anti-apoptotic and pro-apoptotic effects. In the normal cells, MEL possesses antioxidant property and has an anti-apoptotic effect, while in the cancer [...] Read more.

Melatonin (N-acetyl-5-methoxytryptamine MEL) is an indolamine that has antioxidant, anti-inflammatory and anti-tumor properties. Moreover, MEL is capable of exhibiting both anti-apoptotic and pro-apoptotic effects. In the normal cells, MEL possesses antioxidant property and has an anti-apoptotic effect, while in the cancer cells it has pro-apoptotic action. We investigated the combined effect of MEL and navitoclax (ABT-737), which promotes cell death, on the activation of proliferation in acute promyelocytic leukemia on a cell model HL-60. The combined effect of these compounds leads to a reduction of the index of mitotic activity. The alterations in the level of anti- and pro-apoptotic proteins such as BclxL, Bclw, Mcl-1, and BAX, membrane potential, Ca²⁺ retention capacity, and ROS production under the combined action of MEL and ABT-737 were performed. We obtained that MEL in combination with ABT-737 decreased Ca²⁺ capacity, dropped membrane potential, increased ROS production, suppressed the expression of anti-apoptotic proteins such as BclxL, Bclw, and Mcl-1, and enhanced the expression of pro-apoptotic BAX. Since, MEL modulates autophagy and endoplasmic reticulum (ER) stress in cancer cells, the combined effect of MEL and ABT-737 on the expression of ER stress and autophagy markers was checked. The combined effect of MEL and ABT-737 (0.2 μM) increased the expression of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), leading to a decrease in the level of binding immunoglobulin protein (BIP) followed by an increase in the level of C/EBP homologous protein (CHOP). In this condition, the expression of ERO1 decreased, which could lead to a decrease in the level of protein disulfide isomerase (PDI). The obtained data suggested that melatonin has potential usefulness in the treatment of cancer, where it is able to modulate ER stress, autophagy and apoptosis. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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26 pages, 4698 KiB

Open AccessArticle

Transcriptomic Insights into the Effect of Melatonin in Saccharomyces cerevisiae in the Presence and Absence of Oxidative Stress

by Mercè Sunyer-Figueres, Jennifer Vázquez, Albert Mas, María-Jesús Torija and Gemma Beltran

Antioxidants 2020, 9(10), 947; https://doi.org/10.3390/antiox9100947 - 1 Oct 2020

Cited by 18 | Viewed by 3896

Abstract

Melatonin is a ubiquitous indolamine that plays important roles in various aspects of biological processes in mammals. In Saccharomyces cerevisiae, melatonin has been reported to exhibit antioxidant properties and to modulate the expression of some genes involved in endogenous defense systems. The [...] Read more.

Melatonin is a ubiquitous indolamine that plays important roles in various aspects of biological processes in mammals. In Saccharomyces cerevisiae, melatonin has been reported to exhibit antioxidant properties and to modulate the expression of some genes involved in endogenous defense systems. The aim of this study was to elucidate the role of supplemented melatonin at the transcriptional level in S. cerevisiae in the presence and absence of oxidative stress. This was achieved by exposing yeast cells pretreated with different melatonin concentrations to hydrogen peroxide and assessing the entry of melatonin into the cell and the yeast response at the transcriptional level (by microarray and qPCR analyses) and the physiological level (by analyzing changes in the lipid composition and mitochondrial activity). We found that exogenous melatonin crossed cellular membranes at nanomolar concentrations and modulated the expression of many genes, mainly downregulating the expression of mitochondrial genes in the absence of oxidative stress, triggering a hypoxia-like response, and upregulating them under stress, mainly the cytochrome complex and electron transport chain. Other categories that were enriched by the effect of melatonin were related to transport, antioxidant activity, signaling, and carbohydrate and lipid metabolism. The overall results suggest that melatonin is able to reprogram the cellular machinery to achieve tolerance to oxidative stress. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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19 pages, 12178 KiB

Open AccessArticle

Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

by Barbara Szeiffova Bacova, Csilla Viczenczova, Katarina Andelova, Matus Sykora, Kiranj Chaudagar, Miroslav Barancik, Michaela Adamcova, Vladimir Knezl, Tamara Egan Benova, Peter Weismann, Jan Slezak and Narcisa Tribulova

Antioxidants 2020, 9(6), 546; https://doi.org/10.3390/antiox9060546 - 22 Jun 2020

Cited by 30 | Viewed by 3589

Abstract

Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and [...] Read more.

Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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Review

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16 pages, 714 KiB

Open AccessReview

Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis—A New Look on an Old Story: A Review

by Andrzej Kazimierz Jaworek, Jacek Cezary Szepietowski, Przemysław Hałubiec, Anna Wojas-Pelc and Jolanta Jaworek

Antioxidants 2021, 10(8), 1179; https://doi.org/10.3390/antiox10081179 - 24 Jul 2021

Cited by 28 | Viewed by 4883

Abstract

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in patients with AD, and are routinely included during assessment of disease severity. Therefore, [...] Read more.

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possesses strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with a focus on the antioxidant and immunomodulatory effects of MT. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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19 pages, 2057 KiB

Open AccessReview

ROS and NO Phytomelatonin-Induced Signaling Mechanisms under Metal Toxicity in Plants: A Review

by Miriam Pardo-Hernández, María López-Delacalle, José Manuel Martí-Guillen, Sara E. Martínez-Lorente and Rosa M. Rivero

Antioxidants 2021, 10(5), 775; https://doi.org/10.3390/antiox10050775 - 13 May 2021

Cited by 39 | Viewed by 4229

Abstract

Metal toxicity in soils, along with water runoff, are increasing environmental problems that affect agriculture directly and, in turn, human health. In light of finding a suitable and urgent solution, research on plant treatments with specific compounds that can help mitigate these effects [...] Read more.

Metal toxicity in soils, along with water runoff, are increasing environmental problems that affect agriculture directly and, in turn, human health. In light of finding a suitable and urgent solution, research on plant treatments with specific compounds that can help mitigate these effects has increased, and thus the exogenous application of melatonin (MET) and its role in alleviating the negative effects of metal toxicity in plants, have become more important in the last few years. MET is an important plant-related response molecule involved in growth, development, and reproduction, and in the induction of different stress-related key factors in plants. It has been shown that MET plays a protective role against the toxic effects induced by different metals (Pb, Cd, Cu, Zn, B, Al, V, Ni, La, As, and Cr) by regulating both the enzymatic and non-enzymatic antioxidant plant defense systems. In addition, MET interacts with many other signaling molecules, such as reactive oxygen species (ROS) and nitric oxide (NO) and participates in a wide variety of physiological reactions. Furthermore, MET treatment enhances osmoregulation and photosynthetic efficiency, and increases the concentration of other important antioxidants such as phenolic compounds, flavonoids, polyamines (PAs), and carotenoid compounds. Some recent studies have shown that MET appeared to be involved in the regulation of metal transport in plants, and lastly, various studies have confirmed that MET significantly upregulated stress tolerance-related genes. Despite all the knowledge acquired over the years, there is still more to know about how MET is involved in the metal toxicity tolerance of plants. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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17 pages, 646 KiB

Open AccessReview

Melatonin for the Management of Preeclampsia: A Review

by Annie Langston-Cox, Sarah A. Marshall, Daisy Lu, Kirsten R. Palmer and Euan M. Wallace

Antioxidants 2021, 10(3), 376; https://doi.org/10.3390/antiox10030376 - 3 Mar 2021

Cited by 26 | Viewed by 4655

Abstract

Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and [...] Read more.

Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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17 pages, 1197 KiB

Open AccessReview

Evidence of Polyphenols Efficacy against Dry Eye Disease

by Gaia Favero, Enrico Moretti, Kristína Krajčíková, Vladimíra Tomečková and Rita Rezzani

Antioxidants 2021, 10(2), 190; https://doi.org/10.3390/antiox10020190 - 28 Jan 2021

Cited by 19 | Viewed by 5279

Abstract

Dry eye disease is a multifactorial pathology compromising the quality of life of patients, resulting in significant damage of the ocular surface and discomfort. The current therapeutical strategies are not able to definitively resolve the underlying causes and stop the symptoms. Polyphenols are [...] Read more.

Dry eye disease is a multifactorial pathology compromising the quality of life of patients, resulting in significant damage of the ocular surface and discomfort. The current therapeutical strategies are not able to definitively resolve the underlying causes and stop the symptoms. Polyphenols are promising natural molecules that are receiving increasing attention for their activity/effects in counteracting the main pathologic mechanisms of dry eye disease and reducing its symptoms. In the present review, a deep literature search focusing on the main polyphenols tested against dry eye disease was conducted, analyzing related in vitro, in vivo, and clinical studies to provide a comprehensive and current review on the state of the art. Polyphenols present multiple effects against dry eye diseases-related ocular surface injury. In particular, the observed beneficial effects of polyphenols on corneal cells are the reduction of the pathological processes of inflammation, oxidative stress, and apoptosis and modulation of the tear film. Due to numerous studies reporting that polyphenols are effective and safe for treating the pathological mechanisms of this ocular surface disease, we believe that future studies should confirm and extend the evidence of polyphenols efficacy in clinical practice against dry eye disease and help to develop new ophthalmic drug(s). Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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29 pages, 1263 KiB

Open AccessReview

Antioxidants in Fish Sperm and the Potential Role of Melatonin

by Francisca Félix, Catarina C. V. Oliveira and Elsa Cabrita

Antioxidants 2021, 10(1), 36; https://doi.org/10.3390/antiox10010036 - 31 Dec 2020

Cited by 41 | Viewed by 7276

Abstract

In recent years, the effects of novel antioxidants have played an important role in the research focusing on fish cell protection. As food demand grows, aquaculture production becomes more intensive, and fish are more exposed to oxidative stress conditions, like high densities, temperature [...] Read more.

In recent years, the effects of novel antioxidants have played an important role in the research focusing on fish cell protection. As food demand grows, aquaculture production becomes more intensive, and fish are more exposed to oxidative stress conditions, like high densities, temperature shifting, frequent fish handling and samplings, and prophylactic or disease treatments, which expose fish to a different environment. Particularly in reproduction, germ cells lose antioxidant capacity with spermatogenesis, as spermatozoa are more prone to oxidative stress. Antioxidants have been used in a variety of fish physiological problems including in reproduction and in the establishment of cryopreservation protocols. From the most used antioxidants to natural plant food and herbs, and endogenously produced antioxidants, like melatonin, a review of the literature available in terms of their effects on the protection of fish spermatozoa is presented here in a classified structure. Several direct and indirect approaches to improve gamete quality using antioxidants administration are mentioned (through feed supplementation or by adding in cryopreservation media), as well as factors affecting the efficiency of these molecules and their mechanisms of action. Special attention is given to the unclear melatonin pathway and its potential scavenger activity to prevent and counteract oxidative stress damage on fish spermatozoa. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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21 pages, 3141 KiB

Open AccessReview

Protective Effects of Melatonin against Severe Burn-Induced Distant Organ Injury: A Systematic Review and Meta-Analysis of Experimental Studies

by Dewan Md. Sumsuzzman, Jeonghyun Choi, Zeeshan Ahmad Khan and Yonggeun Hong

Antioxidants 2020, 9(12), 1196; https://doi.org/10.3390/antiox9121196 - 27 Nov 2020

Cited by 12 | Viewed by 4290

Abstract

Extensive burns result in a local wound response and distant-organ injury (DOI) caused by oxidative-stress and inflammation. Melatonin (MT) shows promise in alleviating oxidative-stress and inflammation, but its role in thermal injury is largely unexplored. The present systematic review and meta-analysis were designed [...] Read more.

Extensive burns result in a local wound response and distant-organ injury (DOI) caused by oxidative-stress and inflammation. Melatonin (MT) shows promise in alleviating oxidative-stress and inflammation, but its role in thermal injury is largely unexplored. The present systematic review and meta-analysis were designed to assess the effects of MT on oxidative-stress and inflammatory markers against severe burn-induced DOI. Mean difference (MD)/standard mean difference (SMD) with 95% confidence interval (CI) were estimated using fixed-effect/random-effects models. Eighteen experimental studies met the inclusion criteria. Compared with the control group, MT significantly decreased the levels of malondialdehyde (SMD, −1.03; 95% CI, −1.30, −0.76, p < 0.00001) and 4-hydroxynonenal (MD, −1.06; 95% CI, −1.57, −0.56, p < 0.0001). Additionally, MT increased the levels of glutathione (SMD, 1.94; 95% CI, 1.27, 2.61, p < 0.00001) and superoxide-dismutase (SMD, 0.76; 95% CI, 0.08, 1.45, p = 0.03). Finally, MT significantly decreased the levels of tumor necrosis factor-α (SMD, −1.34; 95% CI, −1.92 to −0.77; p < 0.00001) and C-reactive protein (MD, −12.67; 95% CI, −16.72 to −8.62; p < 0.00001). Meta-analysis indicates that severe burn followed by immediate MT (10 mg/kg) intervention shows significant beneficial effects after 24-h against DOI by regulating oxidative-stress and the inflammatory response. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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29 pages, 1034 KiB

Open AccessReview

Is Melatonin the Cornucopia of the 21st Century?

by Nadia Ferlazzo, Giulia Andolina, Attilio Cannata, Maria Giovanna Costanzo, Valentina Rizzo, Monica Currò, Riccardo Ientile and Daniela Caccamo

Antioxidants 2020, 9(11), 1088; https://doi.org/10.3390/antiox9111088 - 5 Nov 2020

Cited by 126 | Viewed by 35203

Abstract

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because [...] Read more.

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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21 pages, 3571 KiB

Open AccessReview

Antioxidant and Neuroprotective Effects of Caffeine against Alzheimer’s and Parkinson’s Disease: Insight into the Role of Nrf-2 and A2AR Signaling

by Muhammad Ikram, Tae Ju Park, Tahir Ali and Myeong Ok Kim

Antioxidants 2020, 9(9), 902; https://doi.org/10.3390/antiox9090902 - 22 Sep 2020

Cited by 78 | Viewed by 11585

Abstract

This paper reviews the results of studies conducted on the role of caffeine in the management of different neurological disorders, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). To highlight the potential role of caffeine in managing different neurodegenerative diseases, we identified [...] Read more.

This paper reviews the results of studies conducted on the role of caffeine in the management of different neurological disorders, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). To highlight the potential role of caffeine in managing different neurodegenerative diseases, we identified studies by searching PubMed, Web of Science, and Google Scholar by scrutinizing the lists of pertinent publications. According to the collected overall findings, caffeine may reduce the elevated oxidative stress; inhibit the activation of adenosine A2A, thereby regulating the accumulation of Aβ; reduce the hyperphosphorylation of tau; and reduce the accumulation of misfolded proteins, such as α-synuclein, in Alzheimer’s and Parkinson’s diseases. The studies have suggested that caffeine has promising protective effects against different neurodegenerative diseases and that these effects may be used to tackle the neurological diseases and/or their consequences. Here, we review the ongoing research on the role of caffeine in the management of different neurodegenerative disorders, focusing on AD and PD. The current findings suggest that caffeine produces potent antioxidant, inflammatory, and anti-apoptotic effects against different models of neurodegenerative disease, including AD, PD, and other neurodegenerative disorders. Caffeine has shown strong antagonistic effects against the adenosine A2A receptor, which is a microglial receptor, and strong agonistic effects against nuclear-related factor-2 (Nrf-2), thereby regulating the cellular homeostasis at the brain by reducing oxidative stress, neuroinflammation, regulating the accumulation of α-synuclein in PD and tau hyperphosphorylation, amyloidogenesis, and synaptic deficits in AD, which are the cardinal features of these neurodegenerative diseases. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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15 pages, 787 KiB

Open AccessReview

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

by Nadia Sadanandan, Blaise Cozene, Justin Cho, You Jeong Park, Madeline Saft, Bella Gonzales-Portillo and Cesar V. Borlongan

Antioxidants 2020, 9(8), 672; https://doi.org/10.3390/antiox9080672 - 28 Jul 2020

Cited by 24 | Viewed by 6099

Abstract

Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke [...] Read more.

Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke. Full article

(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)

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