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Role of Natural Antioxidants in Free Radical Biology and Human Health

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 54710

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Dr. Kavindra K. Kesari

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Department of Applied Physics, Aalto University, Espoo 00076, Finland
Interests: testicular cancer; infertility; Alzheimer’s disease; cancer therapeutic; neurotoxicity; brain cancer; nanoparticle research; radiation research; bioinformatics; cell and structural biology
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Prof. Dr. Dhruv Kumar

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Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sec-125, Noida 201313, India
Interests: autophagy; bioinformatics; cancer prevention; cancer therapeutics; cancer genomics; cancer proteomics; cancer stem cell; cancer metabolism; drug discovery; tumor-microenvironment; translational cancer research
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Dr. Niraj Kumar Jha

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Department of Biotechnology, Sharda University, Greater Noida, India
Interests: natural products; neurodegenerative disorders; neuro oncology; signalling and neurotherapeutics
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Prof. Dr. Janne Ruokolainen

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Department of Applied Physics, School of Science, Aalto University, Espoo, Finland
Interests: transmission electron microscopy; scanning electron microscopy; genotoxicity; cancer therapeutic; neurotoxicity; nanoparticle research; cell and structural biology; molecular materials; nanocellulose; biocomputation
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Special Issue Information

Dear Colleagues,

In last few decades, the development of global industrialization has led to the generation of huge amounts of air and water pollutants as well as radiation through different sources, which directly affects human life. Day after day, individuals are being exposed to chemicals, pollutants, and radiation that react with their genetic material, causing countless numbers of health-related issues through the generation of free radicals as well as reactive oxygen and nitrogen species. Considering the effect of mutagenic factors—i.e., radiation (ionizing and non-ionizing), chemicals, toxic metals, lifestyle factors (junk food and viral infections), climate change, etc.—on free radical generation in human body is of great interest for the subsequent exploration of protective measures by developing experimental setups. Briefly, research focused on molecular and integrative toxicology could be helpful in understanding the mechanisms of toxicity associated with free radical generation. This represents a key approach for uncovering the molecular mechanisms of antioxidants in preclinical safety assessments, assisting in toxicological research and drug discovery. The broad applications of molecular toxicology provide examples of the thriving application of gene expression markers in several categories of clinically relevant toxicity. Moreover, this field is specifically associated with the effects of a variety of chemical components on living organisms. There are several mechanisms underlying toxicity in which various pathways are triggered to damage components of cells and further lead to clinical manifestations of various ailments, including cancer and neurological abnormalities.

Investigating the crucial interplay between such events is relevant to improving the actual treatment of these impairments and will eventually lead to the development of effective therapeutic approaches for treating the diseases associated with free radicals.

The aim of this Special Issue is to present a series of research articles and reviews from a diverse group of the scientific community, sharing their research work on the role of natural antioxidants in free radical research and environmental toxicity associated with human health. This Special Issue will present various aspects of the recent progress in the field of plant-derived bioactive compounds, and their role as antioxidants and the clinical manifestations of various disorders. This issue will include cell signaling, various risk factors, mechanistic insights into metal and nanoparticle toxicity, neural toxicity, nongenotoxic carcinogenicity, immune and idiosyncratic toxicity, prevention, and biomarkers associated with free radical and antioxidant biology and their use in therapeutic strategies. In particular, this issue will provide valuable insights for researchers and clinicians with an interest in toxicological research and cellular impairments, with a special emphasis on therapeutic advancement through natural antioxidants.

Special attention will be given to exploring natural bioactive compounds extracted from plants for the treatment of critical diseases—more specifically, the utilization and transformation of these bioactive compounds into nanoparticles and the direct targeting of affected cells and tissues of the organs associated with disease.

Dr. Kavindra Kumar Kesari

Prof. Dr. Dhruv Kumar
Dr. Niraj Kumar Jha
Prof. Dr. Janne Ruokolainen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (8 papers)

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Research

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14 pages, 2139 KiB

Open AccessArticle

Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats

by Seenipandi Arunachalam, M. F. Nagoor Meeran, Sheikh Azimullah, Charu Sharma, Sameer N. Goyal and Shreesh Ojha

Antioxidants 2021, 10(6), 984; https://doi.org/10.3390/antiox10060984 - 21 Jun 2021

Cited by 38 | Viewed by 3750

Abstract

The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is often limited by its cardiotoxic effects. Thus, for improving usage of DOX, the aim of this study was to assess the cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced acute cardiotoxicity and examine underlying molecular mechanisms that contribute to these effects. To induce acute cardiotoxicity male albino Wistar rats were injected with single dose intraperitoneal DOX (12.5 mg/kg). The rats were treated with NERO (50 mg/kg, orally) for five days. DOX-injected rats showed elevated levels of cardiac marker enzymes and enhanced oxidative stress markers along with altered Nrf2/Keap1/HO-1 signaling pathways. DOX administration also induced the activation of NF-κB/MAPK signaling and increased the levels and expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) as well as expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX also triggered DNA damage and apoptotic cell death in the myocardium. Additionally, histological studies revealed structural alterations of the myocardium. NERO treatment exhibited protection against the deleterious results of DOX on myocardium, as evidenced by the restoration of altered biochemical parameters, mitigated oxidative stress, inflammation, and apoptosis. The findings of the present study demonstrate that NERO provides cardioprotective effects against DOX-induced acute cardiotoxicity attributed to its potent antioxidant, anti-inflammatory, and antiapoptotic activities through modulating cellular signaling pathways. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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13 pages, 3485 KiB

Open AccessArticle

RedEfish: Generation of the Polycistronic mScarlet: GSG-T2A: Ttpa Zebrafish Line

by Brian Head, Jane La Du, Carrie Barton, Jie Zhang, Carmen Wong, Emily Ho, Robyn L. Tanguay and Maret G. Traber

Antioxidants 2021, 10(6), 965; https://doi.org/10.3390/antiox10060965 - 16 Jun 2021

Cited by 1 | Viewed by 3688

Abstract

The vitamin E regulatory protein, the alpha-tocopherol transfer protein (Ttpa), is necessary for zebrafish embryo development. To evaluate zebrafish embryo Ttpa function, we generated a fluorescent-tagged zebrafish transgenic line using CRISPR-Cas9 technology. One-cell stage embryos (from Casper (colorless) zebrafish adults) were injected the mScarlet coding sequence in combination with cas9 protein complexed to single guide RNA molecule targeting 5′ of the ttpa genomic region. Embryos were genotyped for proper insertion of the mScarlet coding sequence, raised to adulthood and successively in-crossed to produce the homozygote RedEfish (mScarlet: GSG-T2A: Ttpa). RedEfish were characterized by in vivo fluorescence detection at 1, 7 and 14 days post-fertilization (dpf). Fluorescent color was detectable in RedEfish embryos at 1 dpf; it was distributed throughout the developing brain, posterior tailbud and yolk sac. At 7 dpf, the RedEfish was identifiable by fluorescence in olfactory pits, gill arches, pectoral fins, posterior tail region and residual yolk sac. Subsequently (14 dpf), the mScarlet protein was found in olfactory pits, distributed throughout the digestive tract, along the lateral line and especially in caudal vertebrae. No adverse morphological outcomes or developmental delays were observed. The RedEfish will be a powerful model to study Ttpa function during embryo development. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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16 pages, 1222 KiB

Open AccessArticle

Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats

by Margarita R. Ramis, Fiorella Sarubbo, David Moranta, Silvia Tejada, Jerònia Lladó, Antoni Miralles and Susana Esteban

Antioxidants 2021, 10(4), 621; https://doi.org/10.3390/antiox10040621 - 19 Apr 2021

Cited by 5 | Viewed by 2496

Abstract

A healthy aging process is a requirement for good life quality. A relationship between physical activity, the consumption of antioxidants and brain health has been stablished via the activation of pathways that reduce the harmful effects of oxidative stress, by inducing enzymes such as SIRT1, which is a protector of brain function. We analyzed the cognitive and neurochemical effects of applying physical exercise in elderly rats, alone or in combination with the antioxidant catechin. Several tests of spatial and episodic memory and motor coordination were evaluated. In addition, brain monoaminergic neurotransmitters and SIRT1 protein levels were assessed in the brains of the same rats. The results show that physical activity by itself improved age-related memory and learning deficits, correlating with the restoration of brain monoaminergic neurotransmitters and SIRT1 protein levels in the hippocampus. The administration of the antioxidant catechin along with the exercise program enhanced further the monoaminergic pathways, but not the other parameters studied. These results agree with previous reports revealing a neuroprotective effect of physical activity, probably based on its ability to improve the redox status of the brain, demonstrating that exercise at an advanced age, combined with the consumption of antioxidants, could produce favorable effects in terms of brain health. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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17 pages, 3629 KiB

Open AccessArticle

Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes

by Jiahui Zhang, Fnu Anshul, Deepak K. Malhotra, Juan Jaume, Lance D. Dworkin and Rujun Gong

Antioxidants 2021, 10(1), 138; https://doi.org/10.3390/antiox10010138 - 19 Jan 2021

Cited by 15 | Viewed by 5053

Abstract

Psychiatric use of lithium has been associated with hypoglycemic effects, but its effect on type 1 diabetes mellitus (T1D) is unknown. In streptozotocin (STZ) induced murine models of T1D, microdose lithium therapy improved hyperglycemia, attenuated body weight loss and prevented early signs of diabetic kidney injury. This beneficial effect was associated with preservation of pancreatic islet histology and β-cell production of insulin as well as mitigated oxidative damage of islets. Mechanistically, lithium in islets cells induced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), the major molecular target of lithium that has been recently implicated in non-canonical regulation of Nrf2 activity. In turn, Nrf2 antioxidant response was potentiated in islets, marked by nuclear translocation of Nrf2 and augmented expression of its target antioxidant enzyme heme oxygenase 1 (HO-1). Conversely, cotreatment with trigonelline, a selective blockade of Nrf2, offset the lithium enhanced Nrf2 antioxidant response in islets, blunted the protective effect of lithium on pancreatic islets and β-cells, and abolished the hypoglycemic activity of lithium in STZ-injured mice. Collectively, our findings suggest that microdose lithium confers a protective effect on islet β-cells via targeting the GSK3β-regulated Nrf2 antioxidant response and thereby ameliorates T1D and its related kidney impairment. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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Review

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18 pages, 2031 KiB

Open AccessReview

Antioxidant Role of Kaempferol in Prevention of Hepatocellular Carcinoma

by Nidhi Sharma, Subhrajit Biswas, Noura Al-Dayan, Alaa Saud Alhegaili and Maryam Sarwat

Antioxidants 2021, 10(9), 1419; https://doi.org/10.3390/antiox10091419 - 05 Sep 2021

Cited by 50 | Viewed by 4318

Abstract

Reactive oxygen species (ROS) are noxious to cells because their increased level interacts with the body’s defense mechanism. These species also cause mutations and uncontrolled cell division, resulting in oxidative stress (OS). Prolonged oxidative stress is responsible for incorrect protein folding in the endoplasmic reticulum (ER), causing a stressful condition, ER stress. These cellular stresses (oxidative stress and ER stress) are well-recognized biological factors that play a prominent role in the progression of hepatocellular carcinoma (HCC). HCC is a critical global health problem and the third leading cause of cancer-related mortality. The application of anti-oxidants from herbal sources significantly reduces oxidative stress. Kaempferol (KP) is a naturally occurring, aglycone dietary flavonoid that is present in various plants (Crocus sativus, Coccinia grandis, Euphorbia pekinensis, varieties of Aloe vera, etc.) It is capable of interacting with pleiotropic proteins of the human body. Efforts are in progress to develop KP as a potential candidate to prevent HCC with no adverse effects. This review emphasizes the molecular mechanism of KP for treating HCC, targeting oxidative stress. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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10 pages, 1296 KiB

Open AccessReview

Oxidative-Stress-Induced Cellular Toxicity and Glycoxidation of Biomolecules by Cosmetic Products under Sunlight Exposure

by Syed Faiz Mujtaba, Agha Parvez Masih, Ibrahim Alqasmi, Ahmad Alsulimani, Faizan Haider Khan and Shafiul Haque

Antioxidants 2021, 10(7), 1008; https://doi.org/10.3390/antiox10071008 - 23 Jun 2021

Cited by 12 | Viewed by 3611

Abstract

Cosmetics, commonly known as ‘makeup’ are products that can enhance the appearance of the human body. Cosmetic products include hair dyes, shampoos, skincare, sunscreens, kajal, and other makeup products. Cosmetics are generally applied throughout the face and over the neck region. Sunlight has different wavelengths of light, which include UV-A, UV-B, UV-C, and other radiations. Most cosmetic products have absorption maxima (λmax) in the range of visible light and UV-R. The effect of light-induced photosensitization of cosmetic products, which results in the production of free radicals through type-I and type-II photosensitization mechanisms. Free-radicals-mediated DNA damage and oxidative stress are common consequences of cosmetic phototoxicity. Cosmetic phototoxicity may include percutaneous absorption, skin irritation, eye irritation, photosensitization, mutagenicity, and genotoxicity. Oxidative stress induces membrane lipid peroxidation, glycoxidation, and protein covalent modifications, resulting in their dysfunction. Natural antioxidants inhibit oxidative-stress-induced cosmetic toxicity. Sunlight-induced photodegradation and accumulation of cosmetic photoproducts are also a matter of serious concern. India has tropical weather conditions throughout the year and generally, a majority of human activities such as commerce, agriculture, sports, etc. are performed under bright sunlight conditions. Thus, more focused and dedicated research is warranted to explore the effects of cosmetics on oxidative stress, glycoxidation of biomolecules, and photoproducts accumulation for its total human safety. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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20 pages, 963 KiB

Open AccessReview

Salvadora persica: Nature’s Gift for Periodontal Health

by Mohamed Mekhemar, Mathias Geib, Manoj Kumar, Radha, Yasmine Hassan and Christof Dörfer

Antioxidants 2021, 10(5), 712; https://doi.org/10.3390/antiox10050712 - 30 Apr 2021

Cited by 19 | Viewed by 5058

Abstract

Salvadora persica (SP) extract, displays very valuable biotherapeutic capacities such as antimicrobial, antioxidant, antiparasitic and anti-inflammatory effects. Numerous investigations have studied the pharmacologic actions of SP in oral disease therapies but its promising outcomes in periodontal health and treatment are not yet entirely described. The current study has been planned to analyze the reported effects of SP as a support to periodontal therapy to indorse regeneration and healing. In consort with clinical trials, in vitro investigations show the advantageous outcomes of SP adjunctive to periodontal treatment. Yet, comprehensive supplementary preclinical and clinical investigations at molecular and cellular levels are indispensable to reveal the exact therapeutic mechanisms of SP and its elements for periodontal health and therapy. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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28 pages, 3622 KiB

Open AccessReview

Oxidative Stress in Cancer Cell Metabolism

by Saniya Arfin, Niraj Kumar Jha, Saurabh Kumar Jha, Kavindra Kumar Kesari, Janne Ruokolainen, Shubhadeep Roychoudhury, Brijesh Rathi and Dhruv Kumar

Antioxidants 2021, 10(5), 642; https://doi.org/10.3390/antiox10050642 - 22 Apr 2021

Cited by 231 | Viewed by 25136

Abstract

Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro- and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)

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