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Redox Modulation: Restoring Homeostasis with Antioxidants

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 27577

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Special Issue Editors

Prof. Dr. Guido R.M.M. Haenen

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Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
Interests: molecular biology; cell biology; biochemistry; analytical chemistry; pharmacy; medical chemistry; clinical pharmacology; toxicology; reactive oxygen species; free radicals; antioxidants; oxidative stress; redox modulation; nutrition; flavonoids; thiols; glutathione; reactive intermediates; lipid peroxidation; kinetics; structure activity relationship; biomarkers
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Dr. Mohamed Moalin

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Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands
Interests: redox modulation; antioxidants; flavonoids; synthesis of antioxidants; quantum molecular calculations; structure activity relationship
Special Issues, Collections and Topics in MDPI journals

Dr. Ming Zhang

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Guest Editor

Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
Interests: redox modulation; antioxidants; flavonoids; structure activity relationship; free radicals; reactive oxygen species; traditional Chinese medicine

Special Issue Information

Dear Colleagues,

Redox generates energy that flows through networks, which fuels life. In a healthy body, the redox energy is high and kept within very strict limits. A disturbance of this homeostasis is key in the etiology of many diseases. Antioxidants can interact with molecules in the redox network to regain homeostasis. This Special Issue is dedicated to unraveling the molecular mechanism of redox modulation by antioxidants. Of special interest is the relationship between the molecular characteristics of antioxidants and their redox modulating activity. This knowledge will help us to differentiate between antioxidants and to select the appropriate antioxidant for a specific disorder.

Prof. Dr. Guido Haenen
Ms. Ming Zhang
Dr. Mohamed Moalin
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

antioxidants
adaptation
flavonoids
homeostasis
free radical scavenging
antioxidant network
redox modulation
structure–activity relationship

Published Papers (5 papers)

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Research

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16 pages, 4062 KiB

Open AccessArticle

GPx8 Expression in Rat Oocytes, Embryos, and Female Genital Organs During Preimplantation Period of Pregnancy

by Jozef Mihalik, Andrea Kreheľová, Veronika Kovaříková, Peter Solár, Iveta Domoráková, Andriana Pavliuk-Karachevtseva, Alena Hladová, Silvia Rybárová and Ingrid Hodorová

Int. J. Mol. Sci. 2020, 21(17), 6313; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176313 - 31 Aug 2020

Cited by 5 | Viewed by 2197

Abstract

This study aimed to detect the presence of glutathione peroxidase 8 (GPx8) in rat during preimplantation period of pregnancy. Females were killed on first (D1), third (D3), and fifth (D5) day of pregnancy. The presence of GPx8 in embryos was detected under the confocal microscope, the presence of GPx8 in genital organs was confirmed immunohistochemically, and the amount of GPx8 was determined using densitometry. We found that GPx8 is dispersed in the cytoplasm of oocytes, while after fertilization, it is concentrated in granules. From 4-cell stage till blastocyst, GPx8 reaction was found in the perinuclear region. In the ovary, GPx8 was seen in granulosa-lutein cells, in plasma of blood vessels, and inside Graafian follicles. In oviduct, GPx8 was detected in the plasma and in the extracellular matrix (ECM). Moreover, epithelial cells of isthmus were positive. In uterus, GPx8 was observed in the uterine glands, in the plasma, and in ECM. On D5, the enzyme disappeared from the uterine glands and appeared in fibroblasts. Densitometry revealed that the highest amount of GPx8 was on D1 and subsequently declined. To our knowledge, this is the first paper describing GPx8 presence in the oocytes, preimplantation embryos, and female genital organs in mammals. Our results improve the understanding of antioxidant enzymes presence during pregnancy in defense against oxidative stress, which is considered to be one of the main causes of infertility. Full article

(This article belongs to the Special Issue Redox Modulation: Restoring Homeostasis with Antioxidants)

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16 pages, 2709 KiB

Open AccessArticle

The Flow of the Redox Energy in Quercetin during Its Antioxidant Activity in Water

by Zhengwen Li, Mohamed Moalin, Ming Zhang, Lily Vervoort, Erik Hursel, Alex Mommers and Guido R. M. M. Haenen

Int. J. Mol. Sci. 2020, 21(17), 6015; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176015 - 21 Aug 2020

Cited by 9 | Viewed by 2445

Abstract

Most studies on the antioxidant activity of flavonoids like Quercetin (Q) do not consider that it comprises a series of sequential reactions. Therefore, the present study examines how the redox energy flows through the molecule during Q’s antioxidant activity, by combining experimental data with quantum calculations. It appears that several main pathways are possible. Pivotal are subsequently: deprotonation of the 7-OH group; intramolecular hydrogen transfer from the 3-OH group to the 4-Oxygen atom; electron transfer leading to two conformers of the Q radical; deprotonation of the OH groups in the B-ring, leading to three different deprotonated Q radicals; and finally electron transfer of each deprotonated Q radical to form the corresponding quercetin quinones. The quinone in which the carbonyl groups are the most separated has the lowest energy content, and is the most abundant quinone. The pathways are also intertwined. The calculations show that Q can pick up redox energy at various sites of the molecule which explains Q’s ability to scavenge all sorts of reactive oxidizing species. In the described pathways, Q picked up, e.g., two hydroxyl radicals, which can be processed and softened by forming quercetin quinone. Full article

(This article belongs to the Special Issue Redox Modulation: Restoring Homeostasis with Antioxidants)

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15 pages, 2315 KiB

Open AccessArticle

Dysregulated Cardiac IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity

by Saeed Y. Aghdam, Doreswamy Kenchegowda, Neel K. Sharma, Gregory P. Holmes-Hampton, Betre Legesse, Maria Moroni and Sanchita P. Ghosh

Int. J. Mol. Sci. 2020, 21(14), 5049; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145049 - 17 Jul 2020

Cited by 5 | Viewed by 2071

Abstract

Acute exposure to ionizing radiation leads to Hematopoietic Acute Radiation Syndrome (H-ARS). To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, adult males of two strains of minipig, one with higher radiosensitivity, the Gottingen minipig (GMP), and another strain with comparatively lower radiosensitivity, the Sinclair minipig (SMP), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling is associated with radiation sensitivity and regulation of cardiovascular homeostasis, we investigated the link between dysregulation of cardiac IGF-1 signaling and radiosensitivity. The adult male GMP; n = 48, and SMP; n = 24, were irradiated using gamma photons at 1.7–2.3 Gy doses. The animals that survived to day 45 after irradiation were euthanized and termed the survivors. Those animals that were euthanized prior to day 45 post-irradiation due to severe illness or health deterioration were termed the decedents. Cardiac tissue analysis of unirradiated and irradiated animals showed that inter-strain radiosensitivity and survival outcomes in H-ARS are associated with activation status of the cardiac IGF-1 signaling and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant gene expression. Our data link H-ARS with dysregulation of cardiac IGF-1 signaling, and highlight the role of oxidative stress and cardiac antioxidant response in radiation sensitivity. Full article

(This article belongs to the Special Issue Redox Modulation: Restoring Homeostasis with Antioxidants)

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14 pages, 3650 KiB

Open AccessArticle

Delocalization of the Unpaired Electron in the Quercetin Radical: Comparison of Experimental ESR Data with DFT Calculations

by Zhengwen Li, Mohamed Moalin, Ming Zhang, Lily Vervoort, Alex Mommers and Guido R.M.M. Haenen

Int. J. Mol. Sci. 2020, 21(6), 2033; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062033 - 16 Mar 2020

Cited by 13 | Viewed by 3047

Abstract

In the antioxidant activity of quercetin (Q), stabilization of the energy in the quercetin radical (Q^•) by delocalization of the unpaired electron (UE) in Q^• is pivotal. The aim of this study is to further examine the delocalization of the UE in Q^•, and to elucidate the importance of the functional groups of Q for the stabilization of the UE by combining experimentally obtained spin resonance spectroscopy (ESR) measurements with theoretical density functional theory (DFT) calculations. The ESR spectrum and DFT calculation of Q^• and structurally related radicals both suggest that the UE of Q^• is mostly delocalized in the B ring and partly on the AC ring. The negatively charged oxygen groups in the B ring (3′ and 4′) of Q^• have an electron-donating effect that attract and stabilize the UE in the B ring. Radicals structurally related to Q^• indicate that the negatively charged oxygen at 4′ has more of an effect on concentrating the UE in ring B than the negatively charged oxygen at 3′. The DFT calculation showed that an OH group at the 3-position of the AC ring is essential for concentrating the radical on the C2–C3 double bond. All these effects help to explain how the high energy of the UE is captured and a stable Q^• is generated, which is pivotal in the antioxidant activity of Q. Full article

(This article belongs to the Special Issue Redox Modulation: Restoring Homeostasis with Antioxidants)

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Review

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27 pages, 5123 KiB

Open AccessReview

ABTS/PP Decolorization Assay of Antioxidant Capacity Reaction Pathways

by Igor R. Ilyasov, Vladimir L. Beloborodov, Irina A. Selivanova and Roman P. Terekhov

Int. J. Mol. Sci. 2020, 21(3), 1131; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031131 - 08 Feb 2020

Cited by 222 | Viewed by 16953

Abstract

The 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^•+) radical cation-based assays are among the most abundant antioxidant capacity assays, together with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-based assays according to the Scopus citation rates. The main objective of this review was to elucidate the reaction pathways that underlie the ABTS/potassium persulfate decolorization assay of antioxidant capacity. Comparative analysis of the literature data showed that there are two principal reaction pathways. Some antioxidants, at least of phenolic nature, can form coupling adducts with ABTS^•+, whereas others can undergo oxidation without coupling, thus the coupling is a specific reaction for certain antioxidants. These coupling adducts can undergo further oxidative degradation, leading to hydrazindyilidene-like and/or imine-like adducts with 3-ethyl-2-oxo-1,3-benzothiazoline-6-sulfonate and 3-ethyl-2-imino-1,3-benzothiazoline-6-sulfonate as marker compounds, respectively. The extent to which the coupling reaction contributes to the total antioxidant capacity, as well as the specificity and relevance of oxidation products, requires further in-depth elucidation. Undoubtedly, there are questions as to the overall application of this assay and this review adds to them, as specific reactions such as coupling might bias a comparison between antioxidants. Nevertheless, ABTS-based assays can still be recommended with certain reservations, particularly for tracking changes in the same antioxidant system during storage and processing. Full article

(This article belongs to the Special Issue Redox Modulation: Restoring Homeostasis with Antioxidants)

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