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Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Antioxidant Enzyme Systems".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 31336

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Dr. Gianna Ferretti

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Department of Clinical Science and Odontostomatology, Marche Polytechnic University, Via Brecce Bianche, 60131 Ancona, Italy
Interests: lipid peroxidation; lipoprotein; biological membrane; antioxidants; reactive oxygen species; paraoxonase
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Dear Colleagues,

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced by living organisms as a result of normal cellular metabolism. At low to moderate concentrations, they regulate cellular processes, but, at high concentrations, they can adversely modify cellulars lipids, proteins, and DNA. Free radicals and oxidative stress are associated chronic diseases in humans and are even thought to be involved in the ageing process. Human cells possess several mechanisms to protect against oxidative stress, including antioxidants, such as, uric acid, coenzyme Q, and glutathione, and enzymes (including catalase, superoxide dismutase, and glutathione peroxidase).

Diet is also important for oxidative stress in humans, as some foods contain antioxidants and other bioactive molecules that have antioxidant properties. These molecules can counteract oxidative stress and protect cellular macromolecules from damage. This Special Issue “Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems” welcomes the submission of manuscripts either describing original research or reviewing the scientific literature, examining the role of endogenous and exogenous antioxidants and the molecular mechanisms involved in their physiological roles.

Prof. Dr. Gianna Ferretti
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

antioxidant
oxidant
oxidative stress
reactive oxygen species
reactive nitrogen species

Published Papers (7 papers)

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Research

14 pages, 2222 KiB

Open AccessArticle

Bladder Cancer Chemosensitivity Is Affected by Paraoxonase-2 Expression

by Stefania Fumarola, Monia Cecati, Davide Sartini, Gianna Ferretti, Giulio Milanese, Andrea Benedetto Galosi, Valentina Pozzi, Roberto Campagna, Camilla Morresi, Monica Emanuelli and Tiziana Bacchetti

Antioxidants 2020, 9(2), 175; https://doi.org/10.3390/antiox9020175 - 20 Feb 2020

Cited by 25 | Viewed by 3281

Abstract

The goal of the current study was to identify potential roles of paraoxonase-2 in bladder carcinogenesis. T24 bladder cancer cells were transfected with plasmids inducing paraoxonase-2 silencing or overexpression. Upon the selection of clones stably down- or upregulating paraoxonase-2, cell proliferation, migration, and the production of reactive oxygen species were evaluated, before and after treatment with cisplatin and gemcitabine, used alone or in combination. The activity levels of both caspase-3 and caspase-8 were also analyzed. shRNA-mediated gene silencing and the overexpression of paraoxonase-2 revealed that the enzyme was able to promote both the proliferation and migration of T24 cells. Moreover, the knockdown of paraoxonase-2 was significantly associated with a reduced cell viability of T24 cells treated with chemotherapeutic drugs and led to both an increase of reactive oxygen species production and caspase-3 and caspase-8 activation. Conversely, under treatment with anti-neoplastic compounds, a higher proliferative capacity was found in T24 cells overexpressing paraoxonase-2 compared with controls. In addition, upon enzyme upregulation, both the production of reactive oxygen species and activation of caspase-3 and caspase-8 were reduced. Although further analyses will be required to fully understand the involvement of paraoxonase-2 in bladder tumorigenesis and in mechanisms leading to the development of chemoresistance, the data reported in this study seem to demonstrate that the enzyme could exert a great impact on tumor progression and susceptibility to chemotherapy, thus suggesting paraoxonase-2 as a novel and interesting molecular target for effective bladder cancer treatment. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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19 pages, 3666 KiB

Open AccessArticle

Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats

by Weronika Wojnar, Maria Zych, Sławomir Borymski and Ilona Kaczmarczyk-Sedlak

Antioxidants 2020, 9(2), 160; https://doi.org/10.3390/antiox9020160 - 16 Feb 2020

Cited by 25 | Viewed by 4392

Abstract

Prolonged hyperglycemia is one of the main causes of reactive oxygen species and free radicals generation in diabetes which may affect various organs, including the eye. Oxidative damage to proteins and lipids in the eye lens could lead to cataract formation. To cope with oxidative stress, the endogenous antioxidative system may be supported by the supplementation of exogenous antioxidants. The aim of this study was to evaluate the effect of chrysin, a natural flavonoid, on oxidative stress and polyol pathway-related markers in the lenses of streptozotocin-induced type 1 male diabetic rats. Chrysin at doses of 50 and 100 mg/kg was administered by gavage for 28 days. This treatment resulted in a decrease in antioxidative enzymes activity and oxidative stress index. Moreover, chrysin administration elevated the reduced glutathione level in the lenses. A decrease in the markers linked to oxidative damage to proteins and lipids in the lenses was noted, especially after treatment with 50 mg/kg of chrysin. Neither of the chrysin doses affected glycemia-related markers in the serum or altered parameters related to the polyol pathway and advanced glycation end-products level in the lenses of diabetic rats. Upon obtaining results, it can be concluded that chrysin reveals antioxidative activity in the lenses but shows no antihyperglycemic or antiglycation properties. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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10 pages, 916 KiB

Open AccessArticle

Antioxidant and Pro-Oxidant Properties of Carthamus Tinctorius, Hydroxy Safflor Yellow A, and Safflor Yellow A

by Tiziana Bacchetti, Camilla Morresi, Luisa Bellachioma and Gianna Ferretti

Antioxidants 2020, 9(2), 119; https://doi.org/10.3390/antiox9020119 - 29 Jan 2020

Cited by 34 | Viewed by 3682

Abstract

(1) Carthamus Tinctorius L. (safflower) is extensively used in traditional herbal medicine. (2) The aim of this study was to investigate the bioactive properties of polyphenol extracts from flowers of Carthamus Tinctorius (CT) cultivated in Italy. We also evaluated the properties of two bioactive water-soluble flavonoid compounds, hydroxy safflor yellow A (HSYA) and safflor yellow A (SYA), contained in Carthamus Tinctorius petals. (3) The total polyphenol content was 3.5 ± 0.2 g gallic acid equivalent (GAE)/100 g, flavonoids content was 330 ± 23 mg catechin equivalent (CE)/100 g in the flowers. The extract showed a high antioxidant activity evaluated by oxygen radical absorbance capacity (ORAC) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays. In addition, flower extract, SYA, and HSYA were able to reduce the susceptibility of low-density lipoprotein to copper-induced lipid peroxidation. In order to investigate the bioactive properties of flower extract, SYA, and HSYA we also studied their modulatory effect of oxidative stress on human dermal fibroblasts (HuDe) oxidized by tert-butyl hydroperoxide (t-BOOH). The CT extract at concentrations ranging from 0.01–20 μg GAE/mL of polyphenols, exerted a protective effect against t-BOOH triggered oxidative stress. At higher concentration the extract exerted a pro-oxidant effect. Similar results have been obtained using HSYA and SYA. (4) These results demonstrate a biphasic effect exerted by HSYA, SYA, and flower extracts on oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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11 pages, 406 KiB

Open AccessArticle

Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation

by Veronica Tisato, Arianna Romani, Elisa Tavanti, Elisabetta Melloni, Daniela Milani, Gloria Bonaccorsi, Juana M. Sanz, Donato Gemmati, Angelina Passaro and Carlo Cervellati

Antioxidants 2019, 8(8), 287; https://doi.org/10.3390/antiox8080287 - 6 Aug 2019

Cited by 18 | Viewed by 3645

Abstract

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated protein that endows its carrier with (lipo-)lactonase-dependent antioxidative features. Low levels of PON1 activity have been observed in association with obesity, a major risk factor for cardiovascular disease (CVD). Considering the well-recognized atheroprotective role of PON1, exogenous/endogenous factors that might modulate its levels/activity are raising great interest. Since adipokines represent a molecular link between obesity and CVD, we here explored the possible impact of these substances on PON1 activity/expression. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, resistin, leptin, and adiponectin were measured along with arylesterase, paraoxonase, and lactonase activities of PON1 in 107 postmenopausal women. Moreover, the direct effect of resistin on PON1 expression was evaluated in vitro. Multivariate analysis revealed that only resistin was significantly and inversely correlated with PON1-lactonase activities (r = −0.346, p < 0.001) regardless of confounding factors such as age or HDL-cholesterol. It is worth noting that no statistical link was found between adipokine and arylesterase or paraoxonase, the two promiscuous activities of PON1. Notably, resistin down-regulated PON1 expression occurred in hepatocellular carcinoma cultures. Our study suggests that resistin might be a negative modulator of PON1 expression and anti-oxidative activity. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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12 pages, 297 KiB

Open AccessFeature PaperArticle

Effect of Sterigmatocystin or Aflatoxin Contaminated Feed on Lipid Peroxidation and Glutathione Redox System and Expression of Glutathione Redox System Regulatory Genes in Broiler Chicken

by Krisztián Balogh, Benjámin Kövesi, Erika Zándoki, Szabina Kulcsár, Zsolt Ancsin, Márta Erdélyi, Csaba Dobolyi, Ildikó Bata-Vidács, Katalin Inotai, András Szekeres, Miklós Mézes and József Kukolya

Antioxidants 2019, 8(7), 201; https://doi.org/10.3390/antiox8070201 - 28 Jun 2019

Cited by 18 | Viewed by 3124

Abstract

Authors studied the effect of sterigmatocystin from infected corn (STC), purified sterigmatocystin (PSTC), and aflatoxin B1 from infected corn (AFB₁) on lipid peroxidation and glutathione redox parameters, including the expression of their encoding genes in a sub-chronic (14 days) trial. A total of 144 three-week-old cockerels was divided into four experimental groups (n = 36 in each). Control feed was contaminated with STC or PSTC (1590 µg STC/kg or 1570.5 µg STC/kg feed), or with AFB₁ (149.1 µg AFB₁/kg feed). Six birds from each group were sampled at day 1, 2, 3, 7 and 14 of mycotoxin exposure. As parameters of lipid peroxidation, conjugated dienes (CD) and trienes (CT) were measured in the liver, while malondialdehyde (MDA) concentration was determined in blood plasma, red blood cell hemolysate and liver. Reduced glutathione (GSH) concentration and glutathione peroxidase (GPx) activity were determined in the same samples, and expression of glutathione peroxidase 4 (GPX4), glutathione synthetase (GSS) and glutathione reductase (GSR) genes was measured by RT-PCR in the liver. STC, PSTC or AFB₁ caused a slight, but not significant, increase in CD and CT levels; however, in the case of MDA, no increase was found in the liver. Glutathione redox system was activated in the liver by AFB₁, but less markedly by STC/PSTC. PSTC and AFB₁ resulted in a higher expression of GPX4, while GSS expression was down-regulated by AFB₁ on day 1, but up-regulated by STC on day 2 and by both mycotoxins on day 7. However, on day 14, GSS expression was down-regulated by PSTC. Expression of GSR was low on day 1 in AFB₁ and PSTC groups, but later it was up-regulated by AFB₁. The observed changes regarding gene expression strengthen the hypothesis that the mild oxidative stress, caused by the applied STC doses, activates the glutathione redox system of broiler chickens. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

15 pages, 1728 KiB

Open AccessArticle

Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction

by Daniele La Russa, Francesca Giordano, Alessandro Marrone, Maddalena Parafati, Elzbieta Janda and Daniela Pellegrino

Antioxidants 2019, 8(3), 66; https://doi.org/10.3390/antiox8030066 - 16 Mar 2019

Cited by 36 | Viewed by 8585

Abstract

Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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11 pages, 1539 KiB

Open AccessArticle

Evaluation of the AGE/sRAGE Axis in Patients with Multiple Myeloma

by Alessandro Allegra, Caterina Musolino, Elisabetta Pace, Vanessa Innao, Eleonora Di Salvo, Maria Ferraro, Marco Casciaro, Giovanna Spatari, Gennaro Tartarisco, Andrea Gaetano Allegra and Sebastiano Gangemi

Antioxidants 2019, 8(3), 55; https://doi.org/10.3390/antiox8030055 - 4 Mar 2019

Cited by 14 | Viewed by 3029

Abstract

Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets. Full article

(This article belongs to the Special Issue Oxidative Damage: The Role of Endogenous and Exogenous Antioxidant Systems)

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