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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 (20 April 2023) | Viewed by 42992

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Prof. Dr. Serge Ankri

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Guest Editor

Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
Interests: redox biology; oxidative stress; parasites; epigenetics; virulence

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) play a key role in eliciting oxidative stress (OS) response in cells. They are capable of damaging essential biomolecules in cells, such as DNA, proteins, and lipids, and they primarily inhibit cellular functions. During the invasion process, parasites encounter OS in their host. A main source of OS is the generation of ROS by cells of the immune system. Many anti-parasitic drugs are also able to induce oxidative damage directly or indirectly by targeting the antioxidant defence system of the parasite. Parasite redox biology is vital for understanding parasite–host interactions, adaptations, and resistance to redox-active antiparasitic molecules.

We invite you to submit your latest research findings or a review article to this Special Issue, which should be focused on the redox biology of parasites. This research work can be oriented towards the redox changes occuring during differentiation and drastic transitions between environments that take place during parasitic complex life cycles, oxidative stress encountered by parasites in response to the activation of the immune system, the redox biology of intracellular parasites, the development of ROS-generating antiparasitic compounds, the study of redox signalling molecules in parasites, or any other aspect of the redox biology of parasites.

Prof. Dr. Serge Ankri
Guest Editor

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Keywords

Redox biology
Oxidative stress
Parasites
Antioxidant enzymes
Infection process

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 177 KiB

Open AccessEditorial

Insights into the Role of Oxidative Stress and Reactive Oxygen Species in Parasitic Diseases

by Serge Ankri

Antioxidants 2023, 12(5), 1010; https://doi.org/10.3390/antiox12051010 - 27 Apr 2023

Cited by 1 | Viewed by 1200

Abstract

Parasitic infections remain a significant public health challenge in many parts of the world, especially in developing countries [...] Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

Research

Jump to: Editorial, Review

20 pages, 2840 KiB

Open AccessArticle

Iron Uptake Controls Trypanosoma cruzi Metabolic Shift and Cell Proliferation

by Claudia F. Dick, Carolina L. Alcantara, Luiz F. Carvalho-Kelly, Marco Antonio Lacerda-Abreu, Narcisa L. Cunha-e-Silva, José R. Meyer-Fernandes and Adalberto Vieyra

Antioxidants 2023, 12(5), 984; https://doi.org/10.3390/antiox12050984 - 22 Apr 2023

Cited by 2 | Viewed by 2060

Abstract

(1) Background: Ionic transport in Trypanosoma cruzi is the object of intense studies. T. cruzi expresses a Fe-reductase (TcFR) and a Fe transporter (TcIT). We investigated the effect of Fe depletion and Fe supplementation on different structures and functions of T. cruzi epimastigotes in culture. (2) Methods: We investigated growth and metacyclogenesis, variations of intracellular Fe, endocytosis of transferrin, hemoglobin, and albumin by cell cytometry, structural changes of organelles by transmission electron microscopy, O₂ consumption by oximetry, mitochondrial membrane potential measuring JC-1 fluorescence at different wavelengths, intracellular ATP by bioluminescence, succinate-cytochrome c oxidoreductase following reduction of ferricytochrome c, production of H₂O₂ following oxidation of the Amplex^® red probe, superoxide dismutase (SOD) activity following the reduction of nitroblue tetrazolium, expression of SOD, elements of the protein kinase A (PKA) signaling, TcFR and TcIT by quantitative PCR, PKA activity by luminescence, glyceraldehyde-3-phosphate dehydrogenase abundance and activity by Western blotting and NAD⁺ reduction, and glucokinase activity recording NADP⁺ reduction. (3) Results: Fe depletion increased oxidative stress, inhibited mitochondrial function and ATP formation, increased lipid accumulation in the reservosomes, and inhibited differentiation toward trypomastigotes, with the simultaneous metabolic shift from respiration to glycolysis. (4) Conclusion: The processes modulated for ionic Fe provide energy for the T. cruzi life cycle and the propagation of Chagas disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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20 pages, 5414 KiB

Open AccessArticle

Two Distinct Superoxidase Dismutases (SOD) Secreted by the Helminth Parasite Fasciola hepatica Play Roles in Defence against Metabolic and Host Immune Cell-Derived Reactive Oxygen Species (ROS) during Growth and Development

by Nichola Eliza Davies Calvani, Carolina De Marco Verissimo, Heather Louise Jewhurst, Krystyna Cwiklinski, Andrew Flaus and John Pius Dalton

Antioxidants 2022, 11(10), 1968; https://doi.org/10.3390/antiox11101968 - 30 Sep 2022

Cited by 12 | Viewed by 2787

Abstract

The antioxidant superoxide dismutase (SOD) catalyses the dismutation of superoxide, a dangerous oxygen free radical, into hydrogen peroxide and molecular oxygen. Superoxide generation during the oxidative burst of the innate immune system is considered a key component of the host defence against invading pathogens. We demonstrate the presence and differential expression of two SODs in Fasciola hepatica, a leaderless cytosolic (FhSOD1) and an extracellular (FhSOD3) form containing a secretory signal peptide, suggesting that the parasites exploit these enzymes in distinct ways to counteract reactive oxygen species (ROS) produced by cellular metabolism and immune defences. Both enzymes are highly expressed by the infective newly excysted juvenile (NEJ) stages and are found in abundance in their excretory–secretory products (ES), but only FhSOD1 is present in adult ES, suggesting that the antioxidants have different functions and pathways of secretion, and are under separate temporal expression control during the migration, growth, and development of the parasite. Functionally, the recombinant FhSOD1 and FhSOD3 exhibit similar activity against superoxide to their mammalian counterparts. Confocal immuno-localisation studies demonstrated the presence of FhSOD1 and FhSOD3 on the NEJ tegument and parenchyma, supporting our suggestion that these enzymes are secreted during host invasion to protect the parasites from the harmful oxidative bursts produced by the activated innate immune response. By producing superoxide enzymatically in vitro, we were able to demonstrate robust killing of F. hepatica NEJ within 24 h post-excystment, and that the lethal effect of ROS was nullified with the addition of SOD and catalase (the antioxidant enzyme responsible for the dismutation of hydrogen peroxide, a by-product of the SOD reaction). This study further elucidates the mechanism by which F. hepatica protects against ROS derived from cellular metabolism and how the parasite could mitigate damage caused by the host’s immune response to benefit its survival. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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13 pages, 1593 KiB

Open AccessArticle

Insights into the Mechanisms of Lactobacillus acidophilus Activity against Entamoeba histolytica by Using Thiol Redox Proteomics

by Lotem Sarid, Eva Zanditenas, Jun Ye, Meirav Trebicz-Geffen and Serge Ankri

Antioxidants 2022, 11(5), 814; https://doi.org/10.3390/antiox11050814 - 22 Apr 2022

Cited by 6 | Viewed by 3106

Abstract

Amebiasis is an intestinal disease transmitted by the protist parasite, Entamoeba histolytica. Lactobacillus acidophilus is a common inhabitant of healthy human gut and a probiotic that has antimicrobial properties against a number of pathogenic bacteria, fungi, and parasites. The aim of this study was to investigate the amebicide activity of L. acidophilus and its mechanisms. For this purpose, E. histolytica and L. acidophilus were co-incubated and the parasite’s viability was determined by eosin dye exclusion. The level of ozidized proteins (OXs) in the parasite was determined by resin-assisted capture RAC (OX–RAC). Incubation with L. acidophilus for two hours reduced the viability of E. histolytica trophozoites by 50%. As a result of the interaction with catalase, an enzyme that degrades hydrogen peroxide (H₂O₂) to water and oxygen, this amebicide activity is lost, indicating that it is mediated by H₂O₂ produced by L. acidophilus. Redox proteomics shows that L. acidophilus triggers the oxidation of many essential amebic enzymes such as pyruvate: ferredoxin oxidoreductase, the lectin Gal/GalNAc, and cysteine proteases (CPs). Further, trophozoites of E. histolytica incubated with L. acidophilus show reduced binding to mammalian cells. These results support L. acidophilus as a prophylactic candidate against amebiasis. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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24 pages, 3188 KiB

Open AccessArticle

Nitric Oxide Resistance in Leishmania (Viannia) braziliensis Involves Regulation of Glucose Consumption, Glutathione Metabolism and Abundance of Pentose Phosphate Pathway Enzymes

by Nathalia Pinho, Ana Cristina Bombaça, Jacek R. Wiśniewski, Geovane Dias-Lopes, Leonardo Saboia-Vahia, Elisa Cupolillo, José Batista de Jesus, Roque P. de Almeida, Gabriel Padrón, Rubem Menna-Barreto and Patricia Cuervo

Antioxidants 2022, 11(2), 277; https://doi.org/10.3390/antiox11020277 - 29 Jan 2022

Cited by 9 | Viewed by 3646

Abstract

In American Tegumentary Leishmaniasis production of cytokines, reactive oxygen species and nitric oxide (NO) by host macrophages normally lead to parasite death. However, some Leishmania braziliensis strains exhibit natural NO resistance. NO-resistant strains cause more lesions and are frequently more resistant to antimonial treatment than NO-susceptible ones, suggesting that NO-resistant parasites are endowed with specific mechanisms of survival and persistence. To tests this, we analyzed the effect of pro- and antioxidant molecules on the infectivity in vitro of L. braziliensis strains exhibiting polar phenotypes of resistance or susceptibility to NO. In addition, we conducted a comprehensive quantitative mass spectrometry-based proteomics analysis of those parasites. NO-resistant parasites were more infective to peritoneal macrophages, even in the presence of high levels of reactive species. Principal component analysis of protein concentration values clearly differentiated NO-resistant from NO-susceptible parasites, suggesting that there are natural intrinsic differences at molecular level among those strains. Upon NO exposure, NO-resistant parasites rapidly modulated their proteome, increasing their total protein content and glutathione (GSH) metabolism. Furthermore, NO-resistant parasites showed increased glucose analogue uptake, and increased abundance of phosphotransferase and G6PDH after nitrosative challenge, which can contribute to NADPH pool maintenance and fuel the reducing conditions for the recovery of GSH upon NO exposure. Thus, increased glucose consumption and GSH-mediated redox capability may explain the natural resistance of L. braziliensis against NO. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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21 pages, 3203 KiB

Open AccessArticle

Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease

by Denerieth Ximena Espinel-Mesa, Clara Isabel González Rugeles, Julio César Mantilla Hernández, Elena E. Stashenko, Carlos Andrés Villegas-Lanau, John Jaime Quimbaya Ramírez and Liliana Torcoroma García Sánchez

Antioxidants 2021, 10(11), 1851; https://doi.org/10.3390/antiox10111851 - 22 Nov 2021

Cited by 6 | Viewed by 3593

Abstract

In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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16 pages, 3061 KiB

Open AccessArticle

Entamoeba histolytica Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization

by Yana Shaulov, Lotem Sarid, Meirav Trebicz-Geffen and Serge Ankri

Antioxidants 2021, 10(8), 1240; https://doi.org/10.3390/antiox10081240 - 2 Aug 2021

Cited by 11 | Viewed by 3498

Abstract

Auranofin (AF), an antirheumatic agent, targets mammalian thioredoxin reductase (TrxR), an important enzyme controlling redox homeostasis. AF is also highly effective against a diversity of pathogenic bacteria and protozoan parasites. Here, we report on the resistance of the parasite Entamoeba histolytica to 2 µM of AF that was acquired by gradual exposure of the parasite to an increasing amount of the drug. AF-adapted E. histolytica trophozoites (AFAT) have impaired growth and cytopathic activity, and are more sensitive to oxidative stress (OS), nitrosative stress (NS), and metronidazole (MNZ) than wild type (WT) trophozoites. Integrated transcriptomics and redoxomics analyses showed that many upregulated genes in AFAT, including genes encoding for dehydrogenase and cytoskeletal proteins, have their product oxidized in wild type trophozoites exposed to AF (acute AF trophozoites) but not in AFAT. We also showed that the level of reactive oxygen species (ROS) and oxidized proteins (OXs) in AFAT is lower than that in acute AF trophozoites. Overexpression of E. histolytica TrxR (EhTrxR) did not protect the parasite against AF, which suggests that EhTrxR is not central to the mechanism of adaptation to AF. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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23 pages, 3661 KiB

Open AccessFeature PaperArticle

New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

by César Díaz-Godínez, Joshue Fabián Jorge-Rosas, Mario Néquiz, Santiago Martínez-Calvillo, Juan P. Laclette, Carlos Rosales and Julio C. Carrero

Antioxidants 2021, 10(6), 974; https://doi.org/10.3390/antiox10060974 - 18 Jun 2021

Cited by 12 | Viewed by 4041

Abstract

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX^® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additionally, we detected the presence of MPO on the cell surface of trophozoites after the interaction with neutrophils and found that luminol and isoluminol, intracellular and extracellular scavengers for MPO derived ROS reduced the amount of NET triggered by amoebas. These data suggest that ROS generated by trophozoites and processed by the extracellular MPO during the contact with neutrophils are required for E. histolytica induced NETosis. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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Review

Jump to: Editorial, Research

12 pages, 948 KiB

Open AccessReview

Ambivalent Roles of Oxidative Stress in Triangular Relationships among Arthropod Vectors, Pathogens and Hosts

by Emmanuel Pacia Hernandez, Anisuzzaman, Md Abdul Alim, Hayato Kawada, Kofi Dadzie Kwofie, Danielle Ladzekpo, Yuki Koike, Takahiro Inoue, Sana Sasaki, Fusako Mikami, Makoto Matsubayashi, Tetsuya Tanaka, Naotoshi Tsuji and Takeshi Hatta

Antioxidants 2022, 11(7), 1254; https://doi.org/10.3390/antiox11071254 - 25 Jun 2022

Cited by 4 | Viewed by 2825

Abstract

Blood-feeding arthropods, particularly ticks and mosquitoes are considered the most important vectors of arthropod-borne diseases affecting humans and animals. While feeding on blood meals, arthropods are exposed to high levels of reactive oxygen species (ROS) since heme and other blood components can induce oxidative stress. Different ROS have important roles in interactions among the pathogens, vectors, and hosts. ROS influence various metabolic processes of the arthropods and some have detrimental effects. In this review, we investigate the various roles of ROS in these arthropods, including their innate immunity and the homeostasis of their microbiomes, that is, how ROS are utilized to maintain the balance between the natural microbiota and potential pathogens. We elucidate the mechanism of how ROS are utilized to fight off invading pathogens and how the arthropod-borne pathogens use the arthropods’ antioxidant mechanism to defend against these ROS attacks and their possible impact on their vector potentials or their ability to acquire and transmit pathogens. In addition, we describe the possible roles of ROS in chemical insecticide/acaricide activity and/or in the development of resistance. Overall, this underscores the importance of the antioxidant system as a potential target for the control of arthropod and arthropod-borne pathogens. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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26 pages, 3691 KiB

Open AccessReview

Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions

by José de Jesús Martínez-González, Alberto Guevara-Flores and Irene Patricia del Arenal Mena

Antioxidants 2022, 11(6), 1102; https://doi.org/10.3390/antiox11061102 - 31 May 2022

Cited by 7 | Viewed by 7868

Abstract

During the evolution of the Earth, the increase in the atmospheric concentration of oxygen gave rise to the development of organisms with aerobic metabolism, which utilized this molecule as the ultimate electron acceptor, whereas other organisms maintained an anaerobic metabolism. Platyhelminthes exhibit both aerobic and anaerobic metabolism depending on the availability of oxygen in their environment and/or due to differential oxygen tensions during certain stages of their life cycle. As these organisms do not have a circulatory system, gas exchange occurs by the passive diffusion through their body wall. Consequently, the flatworms developed several adaptations related to the oxygen gradient that is established between the aerobic tegument and the cellular parenchyma that is mostly anaerobic. Because of the aerobic metabolism, hydrogen peroxide (H₂O₂) is produced in abundance. Catalase usually scavenges H₂O₂ in mammals; however, this enzyme is absent in parasitic platyhelminths. Thus, the architecture of the antioxidant systems is different, depending primarily on the superoxide dismutase, glutathione peroxidase, and peroxiredoxin enzymes represented mainly in the tegument. Here, we discuss the adaptations that parasitic flatworms have developed to be able to transit from the different metabolic conditions to those they are exposed to during their life cycle. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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20 pages, 4718 KiB

Open AccessReview

Reactive Oxygen Species as the Brainbox in Malaria Treatment

by Chinedu Ogbonnia Egwu, Jean-Michel Augereau, Karine Reybier and Françoise Benoit-Vical

Antioxidants 2021, 10(12), 1872; https://doi.org/10.3390/antiox10121872 - 24 Nov 2021

Cited by 29 | Viewed by 4297

Abstract

Several measures are in place to combat the worldwide spread of malaria, especially in regions of high endemicity. In part, most common antimalarials, such as quinolines and artemisinin and its derivatives, deploy an ROS-mediated approach to kill malaria parasites. Although some antimalarials may share similar targets and mechanisms of action, varying levels of reactive oxygen species (ROS) generation may account for their varying pharmacological activities. Regardless of the numerous approaches employed currently and in development to treat malaria, concerningly, there has been increasing development of resistance by Plasmodium falciparum, which can be connected to the ability of the parasites to manage the oxidative stress from ROS produced under steady or treatment states. ROS generation has remained the mainstay in enforcing the antiparasitic activity of most conventional antimalarials. However, a combination of conventional drugs with ROS-generating ability and newer drugs that exploit vital metabolic pathways, such antioxidant machinery, could be the way forward in effective malaria control. Full article

(This article belongs to the Special Issue Oxidative Stress in Parasites)

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