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Molecular Toxicology of Free Radicals: From Molecules to Cells to Tissues

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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 (30 November 2021) | Viewed by 11525

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Special Issue Editor

Prof. Dr. Dimitrios Kouretas

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Guest Editor

Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
Interests: antioxidant activity; plant phenolics; exercise; functional foods; toxicology; redox nutrition; antioxidant administration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will cover new developments in oxidative toxicology in the frame of the fragile interface that emerges under the involvement of physiological mechanisms that govern redox homeostasis from one side and free radical toxicity from the other. Recently, the use of redox biomarkers in the evaluation of the antioxidant profile, both in vitro and in vivo, has surfaced as a potential approach again. Although usually overlooked, recent scientific evidence indicates that redox biomarkers can become a useful tool with great translational potency in the field of redox biology.

Potential topics include but are not limited to the following:

Biomarkers used for the evaluation of in vivo antioxidant mechanisms
Biomarkers for assessing the antioxidant activity of plant compounds in vitro
Estimation of redox status in an exercise context
Antioxidant status in disease using redox biomarkers
Estimation of redox status in aging
Assessment of the antioxidant status of the host after insulted by pathogenic microorganisms

Prof. Dr. Dimitrios Kouretas
Guest Editor

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

oxidative stress
redox regulation
antioxidants
redox biomarkers
polyphenols

Published Papers (4 papers)

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Research

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20 pages, 2082 KiB

Open AccessArticle

Expression Silencing of Glutathione Peroxidase 4 in Mouse Erythroleukemia Cells Delays In Vitro Erythropoiesis

by Marlena Rademacher, Hartmut Kuhn and Astrid Borchert

Int. J. Mol. Sci. 2021, 22(15), 7795; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157795 - 21 Jul 2021

Cited by 2 | Viewed by 2306

Abstract

Among the eight human glutathione peroxidase isoforms, glutathione peroxidase 4 (GPX4) is the only enzyme capable of reducing complex lipid peroxides to the corresponding alcohols. In mice, corruption of the Gpx4 gene leads to embryonic lethality and more detailed expression silencing studies have implicated the enzyme in several physiological processes (e.g., embryonal cerebrogenesis, neuronal function, male fertility). Experiments with conditional knockout mice, in which expression of the Gpx4 gene was silenced in erythroid precursors, indicated a role of Gpx4 in erythropoiesis. To test this hypothesis in a cellular in vitro model we transfected mouse erythroleukemia cells with a Gpx4 siRNA construct and followed the expression kinetics of erythropoietic gene products. Our data indicate that Gpx4 is expressed at high levels in mouse erythroleukemia cells and that expression silencing of the Gpx4 gene delays in vitro erythropoiesis. However, heterozygous expression of a catalytically inactive Gpx4 mutant (Gpx4^+/Sec46Ala) did not induce a defective erythropoietic phenotype in different in vivo and ex vivo models. These data suggest that Gpx4 plays a role in erythroid differentiation of mouse erythroleukemia cells but that heterozygous expression of a catalytically inactive Gpx4 is not sufficient to compromise in vivo and ex vivo erythropoiesis. Full article

(This article belongs to the Special Issue Molecular Toxicology of Free Radicals: From Molecules to Cells to Tissues)

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14 pages, 1220 KiB

Open AccessArticle

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

by Mohammad Bani Ismail, Peramaiyan Rajendran, Hamad Mohammed AbuZahra and Vishnu Priya Veeraraghavan

Int. J. Mol. Sci. 2021, 22(8), 4259; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084259 - 20 Apr 2021

Cited by 21 | Viewed by 2512

Abstract

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity. Full article

(This article belongs to the Special Issue Molecular Toxicology of Free Radicals: From Molecules to Cells to Tissues)

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15 pages, 9166 KiB

Open AccessArticle

Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells

by Magdalena Kluska, Michał Juszczak, Jerzy Żuchowski, Anna Stochmal and Katarzyna Woźniak

Int. J. Mol. Sci. 2021, 22(7), 3520; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073520 - 29 Mar 2021

Cited by 14 | Viewed by 2360

Abstract

Kaempferol is a polyphenol found in a variety of plants. Kaempferol exerts antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives—kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7), isolated from aerial parts of Lens culinaris Medik.—affect the antitumor activity of etoposide in human promyelocytic leukemia (HL-60) cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol and its glycoside derivatives can modulate the activity of etoposide in HL-60 cells and affect its antitumor efficacy in this way. Kaempferol derivatives may have the opposite effect on the action of etoposide in HL-60 cells compared to kaempferol. Full article

(This article belongs to the Special Issue Molecular Toxicology of Free Radicals: From Molecules to Cells to Tissues)

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Review

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12 pages, 1017 KiB

Open AccessReview

Reconceptualization of Hormetic Responses in the Frame of Redox Toxicology

by Zoi Skaperda, Fotios Tekos, Periklis Vardakas, Charitini Nepka and Demetrios Kouretas

Int. J. Mol. Sci. 2022, 23(1), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010049 - 21 Dec 2021

Cited by 14 | Viewed by 3117

Abstract

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date. Full article

(This article belongs to the Special Issue Molecular Toxicology of Free Radicals: From Molecules to Cells to Tissues)

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