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Antioxidants
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Oxidative Stress in Human Toxicology
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Oxidative Stress in Human Toxicology

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 October 2022) | Viewed by 35686

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Tim Hofer

E-Mail Website
Guest Editor
Norwegian Institute of Public Health, Oslo, Norway
Interests: human toxiclogy; aging; neurotoxicology; oxidative stress; metals; xenobiotics

Special Issue Information

Dear Colleagues,

This Special Issue will focus on exposure to foreign chemicals (xenobiotics) that cause oxidative stress.

Certain xenobiotics and/or their metabolites (e.g. quinones) can directly mediate formation of reactive oxygen species (ROS, e.g. peroxides) that may induce damage to biomolecules. Xenobiotics can also indirectly cause oxidative stress by affecting protective proteins (e.g. antioxidant enzymes, catalytic transition metal transporters or chelators), regulation of vitamins, antioxidants, metals, or else, disturbances that may be toxic. Experimental studies in humans and human relevant models including air-breathing mammals (e.g. rodents, dogs, sheep), extensive in vitro (e.g. human cell cultures) studies, but also studies on ‘effect biomarkers of oxidative stress’ (e.g. from lipid peroxidation or nucleic acid damage) often measured in blood or urine, are welcome. Review articles that describe new mechanisms/mode of actions/key events, e.g. full, or parts of Adverse Outcome Pathways (AOPs) related to toxicants and oxidative stress can also be submitted.

Dr. Tim Hofer
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. 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.

Keywords

  • carbonyl
  • DNA damage
  • lipid peroxidation
  • mitochondria
  • nucleic acid
  • protein oxidation
  • radical
  • repair
  • redox cycling

Published Papers (13 papers)

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Editorial

Jump to: Research, Review

3 pages, 185 KiB  
Editorial
Oxidative Stress in Human Toxicology
by Tim Hofer
Antioxidants 2021, 10(8), 1159; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081159 - 21 Jul 2021
Cited by 6 | Viewed by 1991
Abstract
This Special Issue (same name as title) focuses on human exposure to foreign chemicals (xenobiotics) that cause oxidative stress [...] Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)

Research

Jump to: Editorial, Review

23 pages, 2395 KiB  
Article
Sidestream Smoke Extracts from Harm-Reduction and Conventional Camel Cigarettes Inhibit Osteogenic Differentiation via Oxidative Stress and Differential Activation of intrinsic Apoptotic Pathways
by Nicole R. L. Sparks, Lauren M. Walker, Steven R. Sera, Joseph V. Madrid, Michael Hanna, Edward C. Dominguez and Nicole I. zur Nieden
Antioxidants 2022, 11(12), 2474; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11122474 - 15 Dec 2022
Cited by 3 | Viewed by 1916
Abstract
Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke [...] Read more.
Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke being more harmful to developing cells than mainstream smoke. Furthermore, first reports are emerging to suggest a differential impact of conventional versus harm-reduction tobacco products on bone tissue as it develops in the embryo or in vitro. To gather first insight into the molecular mechanism of such differences, we assessed the effect of sidestream smoke solutions from Camel (conventional) and Camel Blue (harm-reduction) cigarettes using a human embryonic stem cell osteogenic differentiation model. Sidestream smoke from the conventional Camel cigarettes concentration-dependently inhibited in vitro calcification triggered by high levels of mitochondrially generated oxidative stress, loss of mitochondrial membrane potential, and reduced ATP production. Camel sidestream smoke also induced DNA damage and caspase 9-dependent apoptosis. Camel Blue-exposed cells, in contrast, invoked only intermediate levels of reactive oxygen species insufficient to activate caspase 3/7. Despite the absence of apoptotic gene activation, damage to the mitochondrial phenotype was still noted concomitant with activation of an anti-inflammatory gene signature and inhibited mineralization. Collectively, the presented findings in differentiating pluripotent stem cells imply that embryos may exhibit low bone mineral density if exposed to environmental smoke during development. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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13 pages, 1599 KiB  
Article
Protective Actions of α-Tocopherol on Cell Membrane Lipids of Paraquat-Stressed Human Astrocytes Using Microarray Technology, MALDI-MS and Lipidomic Analysis
by Laura Sánchez-Sánchez, Roberto Fernández, Maria Dolores Ganfornina, Egoitz Astigarraga and Gabriel Barreda-Gómez
Antioxidants 2022, 11(12), 2440; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11122440 - 10 Dec 2022
Viewed by 1437
Abstract
Cellular senescence is one of the main contributors to some neurodegenerative disorders. The early detection of senescent cells or their related effects is a key aspect in treating disease progression. In this functional deterioration, oxidative stress and lipid peroxidation play an important role. [...] Read more.
Cellular senescence is one of the main contributors to some neurodegenerative disorders. The early detection of senescent cells or their related effects is a key aspect in treating disease progression. In this functional deterioration, oxidative stress and lipid peroxidation play an important role. Endogenous antioxidant compounds, such as α-tocopherol (vitamin E), can mitigate these undesirable effects, particularly lipid peroxidation, by blocking the reaction between free radicals and unsaturated fatty acid. While the antioxidant actions of α-tocopherol have been studied in various systems, monitoring the specific effects on cell membrane lipids at scales compatible with large screenings has not yet been accomplished. Understanding the changes responsible for this protection against one of the consequences of senescence is therefore necessary. Thus, the goal of this study was to determinate the changes in the lipid environment of a Paraquat-treated human astrocytic cell line, as a cellular oxidative stress model, and the specific actions of the antioxidant, α-tocopherol, using cell membrane microarray technology, MALDI-MS and lipidomic analysis. The stress induced by Paraquat exposure significantly decreased cell viability and triggered membrane lipid changes, such as an increase in certain species of ceramides that are lipid mediators of apoptotic pathways. The pre-treatment of cells with α-tocopherol mitigated these effects, enhancing cell viability and modulating the lipid profile in Paraquat-treated astrocytes. These results demonstrate the lipid modulation effects of α-tocopherol against Paraquat-promoted oxidative stress and validate a novel analytical high-throughput method combining cell cultures, microarray technology, MALDI-MS and multivariate analysis to study antioxidant compounds against cellular senescence. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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23 pages, 5420 KiB  
Article
Impact of Glyphosate on the Development of Insulin Resistance in Experimental Diabetic Rats: Role of NFκB Signalling Pathways
by Monisha Prasad, Mansour K. Gatasheh, Mohammad A. Alshuniaber, Rajapandiyan Krishnamoorthy, Ponnulakhmi Rajagopal, Kalaiselvi Krishnamoorthy, Vijayalakshmi Periyasamy, Vishnu Priya Veeraraghavan and Selvaraj Jayaraman
Antioxidants 2022, 11(12), 2436; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11122436 - 09 Dec 2022
Cited by 11 | Viewed by 2412
Abstract
Glyphosate, an endocrine disruptor, has an adverse impact on human health through food and also has the potential to produce reactive oxygen species (ROS), which can lead to metabolic diseases. Glyphosate consumption from food has been shown to have a substantial part in [...] Read more.
Glyphosate, an endocrine disruptor, has an adverse impact on human health through food and also has the potential to produce reactive oxygen species (ROS), which can lead to metabolic diseases. Glyphosate consumption from food has been shown to have a substantial part in insulin resistance, making it a severe concern to those with type 2 diabetes (T2DM). However, minimal evidence exists on how glyphosate impacts insulin-mediated glucose oxidation in the liver. Hence the current study was performed to explore the potential of glyphosate toxicity on insulin signaling in the liver of experimental animals. For 16 weeks, male albino Wistar rats were given 50 mg, 100 mg and 250 mg/kg b. wt. of glyphosate orally. In the current study, glyphosate exposure group was linked to a rise in fasting sugar and insulin as well as a drop in serum testosterone. At the same time, in a dose dependent fashion, glyphosate exposure showed alternations in glucose metabolic enzymes. Glyphosate exposure resulted in a raise in H2O2 formation, LPO and a reduction in antioxidant levels those results in impact on membrane integrity and insulin receptor efficacy in the liver. It also registered a reduced levels of mRNA and protein expression of insulin receptor (IR), glucose transporter-2 (GLUT2) with concomitant increase in the production of proinflammatory factors such as JNK, IKKβ, NFkB, IL-6, IL-1β, and TNF-α as well as transcriptional factors like SREBP1c and PPAR-γ leading to pro-inflammation and cirrhosis in the liver which results in the development of insulin resistance and type 2 diabetes. Our present findings for the first time providing an evidence that exposure of glyphosate develops insulin resistance and type 2 diabetes by aggravating NFkB signaling pathway in liver. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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21 pages, 7281 KiB  
Article
Antiproliferation Effects of Marine-Sponge-Derived Methanol Extract of Theonella swinhoei in Oral Cancer Cells In Vitro
by Jun-Ping Shiau, Ya-Ting Chuang, Jen-Yang Tang, Shu-Rong Chen, Ming-Feng Hou, Jiiang-Huei Jeng, Yuan-Bin Cheng and Hsueh-Wei Chang
Antioxidants 2022, 11(10), 1982; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11101982 - 04 Oct 2022
Cited by 2 | Viewed by 1742
Abstract
The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does [...] Read more.
The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does not affect normal cell viability, exhibiting preferential antiproliferation function. METS exerted more subG1 accumulation, apoptosis induction, cellular and mitochondrial oxidative stress, and DNA damage than normal cells, reverted by oxidative stress inhibitor N-acetylcysteine. This METS-caused oxidative stress was validated to attribute to the downregulation of glutathione. METS activated both extrinsic and intrinsic caspases. DNA double-strand breaks (γH2AX) and oxidative DNA damage (8-hydroxy-2-deoxyguanosine) were stimulated by METS. Therefore, for the first time, this investigation shed light on exploring the functions and responses of preferential antiproliferation of METS in oral cancer cells. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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13 pages, 287 KiB  
Article
Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients
by Chia-Chu Liu, Chia-Fang Wu, Yung-Chin Lee, Tsung-Yi Huang, Shih-Ting Huang, Hsun-Shuan Wang, Jhen-Hao Jhan, Shu-Pin Huang, Ching-Chia Li, Yung-Shun Juan, Tusty-Jiuan Hsieh, Yi-Chun Tsai, Chu-Chih Chen and Ming-Tsang Wu
Antioxidants 2022, 11(1), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010152 - 13 Jan 2022
Cited by 4 | Viewed by 2058
Abstract
Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine’s effects. [...] Read more.
Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine’s effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-β-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
15 pages, 10392 KiB  
Article
Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury
by Hyun-Seung Lee, Sang-Mi Kim, Ja-Hyun Jang, Hyung-Doo Park and Soo-Youn Lee
Antioxidants 2021, 10(6), 895; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10060895 - 02 Jun 2021
Cited by 11 | Viewed by 3100
Abstract
The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5–43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have [...] Read more.
The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5–43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry–based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI (n = 28) and non-VAKI control subjects (n = 69), consisting of the infection subgroup (n = 23), CKD subgroup (n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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14 pages, 2411 KiB  
Article
Characterizing the Role of Biologically Relevant Fluid Dynamics on Silver Nanoparticle Dependent Oxidative Stress in Adherent and Suspension In Vitro Models
by Katherine E. Burns, Robert F. Uhrig, Maggie E. Jewett, Madison F. Bourbon and Kristen A. Krupa
Antioxidants 2021, 10(6), 832; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10060832 - 23 May 2021
Cited by 8 | Viewed by 1776
Abstract
Silver nanoparticles (AgNPs) are being employed in numerous consumer goods and applications; however, they are renowned for inducing negative cellular consequences including toxicity, oxidative stress, and an inflammatory response. Nanotoxicological outcomes are dependent on numerous factors, including physicochemical, biological, and environmental influences. Currently, [...] Read more.
Silver nanoparticles (AgNPs) are being employed in numerous consumer goods and applications; however, they are renowned for inducing negative cellular consequences including toxicity, oxidative stress, and an inflammatory response. Nanotoxicological outcomes are dependent on numerous factors, including physicochemical, biological, and environmental influences. Currently, NP safety evaluations are carried out in both cell-based in vitro and animal in vivo models, with poor correlation between these mechanisms. These discrepancies highlight the need for enhanced exposure environments, which retain the advantages of in vitro models but incorporate critical in vivo influences, such as fluid dynamics. This study characterized the effects of dynamic flow on AgNP behavior, cellular interactions, and oxidative stress within both adherent alveolar (A549) and suspension monocyte (U937) models. This study determined that the presence of physiologically relevant flow resulted in substantial modifications to AgNP cellular interactions and subsequent oxidative stress, as assessed via reactive oxygen species (ROS), glutathione levels, p53, NFκB, and secretion of pro-inflammatory cytokines. Within the adherent model, dynamic flow reduced AgNP deposition and oxidative stress markers by roughly 20%. However, due to increased frequency of contact, the suspension U937 cells were associated with higher NP interactions and intracellular stress under fluid flow exposure conditions. For example, the increased AgNP association resulted in a 50% increase in intracellular ROS and p53 levels. This work highlights the potential of modified in vitro systems to improve analysis of AgNP dosimetry and safety evaluations, including oxidative stress assessments. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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18 pages, 3007 KiB  
Article
The Ameliorative Role of Acacia senegal Gum against the Oxidative Stress and Genotoxicity Induced by the Radiographic Contrast Medium (Ioxitalamate) in Albino Rats
by Islam El-Garawani, Sobhy Hassab El-Nabi, Ahmed El Kattan, Azza Sallam, Sabha Elballat, Shaimaa Abou-Ghanima, Islam H. El Azab, Hesham R. El-Seedi, Shaden A. M. Khalifa and Sawsan El-Shamy
Antioxidants 2021, 10(2), 221; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10020221 - 02 Feb 2021
Cited by 19 | Viewed by 3075
Abstract
Arabic gum (Acacia senegal, AG) is proven effective antioxidant and cytoprotective agent. The present study was designed to test this notion by investigating the possible role of AG against the radiographic contrast medium (Ioxitalamate, Telebrix-35®, TBX)-induced oxidative stress and [...] Read more.
Arabic gum (Acacia senegal, AG) is proven effective antioxidant and cytoprotective agent. The present study was designed to test this notion by investigating the possible role of AG against the radiographic contrast medium (Ioxitalamate, Telebrix-35®, TBX)-induced oxidative stress and genotoxicity. Albino rats were divided into four groups and supplied with either; distilled water, daily 10% (w/v) AG, an intravenous dose of TBX (1600 mg I/kg b.wt) and co-administration of TBX and AG. Rats were sacrificed and blood samples were collected to assess the genotoxicity employing the peripheral blood leucocytes fluorescent double staining; namely the acridine orange/ethidium bromide (AO/EB) staining and alkaline comet assay. Further, chromosomal analyses were done in bone marrow cells. Serum urea and creatinine levels, in addition to malondialdehyde (MDA), nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in kidney tissues were measured. Liquid chromatography-mass spectrophotometry (LC-MS-MS) was performed to identify the chemical composition of AG extract. Kidney functions, single/double-stranded DNA damage, chromosomal aberrations, mitotic index, MDA and NO levels were significantly (p < 0.001) increased in TBX-treated group compared to the control and AG-treated one. Meanwhile, CAT and GSH activities were significantly diminished and the AG supplementation significantly (p < 0.001) ameliorated these effects compared with the control and AG-treated groups. Five compounds have been identified using GNPS networking including 7,3′,4′-Trihydroxyisoflavone, Noscapine, Tetrahydropapaveroline, Costunolide, Hesperidin. In conclusion, results of the present study suggest that AG exerted a protective role against TBX-induced oxidative stress and genotoxicity which may be attributed to the active metabolites in the gum. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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14 pages, 2683 KiB  
Article
Weaning Mice and Adult Mice Exhibit Differential Carbon Tetrachloride-Induced Acute Hepatotoxicity
by Tae Bin Jeong, Doyoung Kwon, Seung Won Son, Sou Hyun Kim, Yun-Hee Lee, Min-Soo Seo, Kil Soo Kim and Young-Suk Jung
Antioxidants 2020, 9(3), 201; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9030201 - 01 Mar 2020
Cited by 16 | Viewed by 4066
Abstract
Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol/kg equal to 15.4 mg/kg) to comparatively evaluate [...] Read more.
Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol/kg equal to 15.4 mg/kg) to comparatively evaluate the time-dependent liver damage and cellular events. CCl4 significantly enhanced the serum alanine aminotransferase/aspartate aminotransferase levels and hepatic centrilobular necrosis in the weaning mice, whereas it induced mild liver injury in the adult mice. CCl4-treated weaning mice exhibited higher hepatic levels of pro-apoptotic proteins (Bax, cleaved caspase-3, -7, and -9), activated MAPKs (p-JNK and p-Erk), and endoplasmic reticulum stress indicators (ATF6 and CHOP) and lower hepatic anti-apoptotic Bcl-2 levels than the adult mice. The weaning mice exhibited enhanced basal hepatic glutathione (GSH) levels due to high glutamate cysteine ligase (GCL) and low anti-cysteine dioxygenase (CDO) enzyme levels. However, CCl4 markedly reduced the hepatic GSH levels only in the weaning mice. Furthermore, higher hepatic levels of oxidative stress-induced malondialdehyde, 4-hydroxynonenal, nitrotyrosine-protein adducts, and oxidized proteins were observed in CCl4-treated weaning mice than in CCl4-treated adult mice. The enhanced levels of hepatic cytochrome P450 (CYP) 2E1 and CYP3A, and decreased hepatic GSH S-transferase (GST)-π and GSH reductase (GR) levels in the weaning mice may contribute to their enhanced susceptibility to liver damage. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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Review

Jump to: Editorial, Research

17 pages, 794 KiB  
Review
Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
by Andrea Capucciati, Fabio A. Zucca, Enrico Monzani, Luigi Zecca, Luigi Casella and Tim Hofer
Antioxidants 2021, 10(6), 824; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10060824 - 21 May 2021
Cited by 18 | Viewed by 3764
Abstract
Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and [...] Read more.
Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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15 pages, 1505 KiB  
Review
High-Content Screening for the Detection of Drug-Induced Oxidative Stress in Liver Cells
by María Teresa Donato and Laia Tolosa
Antioxidants 2021, 10(1), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010106 - 13 Jan 2021
Cited by 26 | Viewed by 3567
Abstract
Drug-induced liver injury (DILI) remains a major cause of drug development failure, post-marketing warnings and restriction of use. An improved understanding of the mechanisms underlying DILI is required for better drug design and development. Enhanced reactive oxygen species (ROS) levels may cause a [...] Read more.
Drug-induced liver injury (DILI) remains a major cause of drug development failure, post-marketing warnings and restriction of use. An improved understanding of the mechanisms underlying DILI is required for better drug design and development. Enhanced reactive oxygen species (ROS) levels may cause a wide spectrum of oxidative damage, which has been described as a major mechanism implicated in DILI. Several cell-based assays have been developed as in vitro tools for early safety risk assessments. Among them, high-content screening technology has been used for the identification of modes of action, the determination of the level of injury and the discovery of predictive biomarkers for the safety assessment of compounds. In this paper, we review the value of in vitro high-content screening studies and evaluate how to assess oxidative stress induced by drugs in hepatic cells, demonstrating the detection of pre-lethal mechanisms of DILI as a powerful tool in human toxicology. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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20 pages, 5876 KiB  
Review
Methylmercury-Mediated Oxidative Stress and Activation of the Cellular Protective System
by Masatake Fujimura and Fusako Usuki
Antioxidants 2020, 9(10), 1004; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9101004 - 16 Oct 2020
Cited by 22 | Viewed by 3051
Abstract
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. In Japan, it is referred to as Minamata disease, which involves two characteristic clinical forms: fetal type and adult type depending on the exposed age. In addition to MeHg burden level, [...] Read more.
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. In Japan, it is referred to as Minamata disease, which involves two characteristic clinical forms: fetal type and adult type depending on the exposed age. In addition to MeHg burden level, individual susceptibility to MeHg plays a role in the manifestation of MeHg toxicity. Research progress has pointed out the importance of oxidative stress in the pathogenesis of MeHg toxicity. MeHg has a high affinity for selenohydryl groups, sulfhydryl groups, and selenides. It has been clarified that such affinity characteristics cause the impairment of antioxidant enzymes and proteins, resulting in the disruption of antioxidant systems. Furthermore, MeHg-induced intracellular selenium deficiency due to the greater affinity of MeHg for selenohydryl groups and selenides leads to failure in the recoding of a UGA codon for selenocysteine and results in the degradation of antioxidant selenoenzyme mRNA by nonsense-mediated mRNA decay. The defect of antioxidant selenoenzyme replenishment exacerbates MeHg-mediated oxidative stress. On the other hand, it has also been revealed that MeHg can directly activate the antioxidant Keap1/Nrf2 signaling pathway. This review summarizes the incidence of MeHg-mediated oxidative stress from the viewpoint of the individual intracellular redox system interactions and the MeHg-mediated aforementioned intracellular events. In addition, the mechanisms of cellular stress pathways and neuronal cell death triggered by MeHg-mediated oxidative stress and direct interactions of MeHg with reactive residues of proteins are mentioned. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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