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Targeting Oxidative Stress for Disease
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Targeting Oxidative Stress for Disease

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

Deadline for manuscript submissions: 31 August 2024 | Viewed by 4601

Special Issue Editors

Prof. Dr. Nada Orsolic

E-Mail Website
Guest Editor
Department of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia
Interests: oxidative stress-induced diseases; natural products; chemoprevention and tumor therapy; bee products and health; radioprotection
Special Issues, Collections and Topics in MDPI journals
Dr. Maja Jazvinšćak Jembrek

E-Mail Website
Guest Editor
1. Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia
2. School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia
Interests: neuroprotection; neurotoxicity; neurodegenerative diseases; oxidative stress; polyphenols; neuropharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress (OS) represents the metabolic state of the organism induced by an increase in the amount of reactive oxygen species (ROS). It is most often associated with neurological diseases but also contributes to the pathogenesis of a number of seemingly unrelated disorders, including type 2 diabetes, cancer, aging, heart and acute renal failure, hypertension, preeclampsia, atherosclerosis and coronary disease, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, glaucoma, osteoporosis, and sexual dysfunction, among others.

This Special Issue aims to provide a comprehensive insight into the understanding of the role of ROS-mediated effects in the physiological, and especially in the pathological processes of diseases’ development. We would like to highlight the possibilities of exploiting OS as a therapeutic approach in the treatment of cancer.

We cordially invite authors to contribute original articles as well as review papers that present advances on the potential of the most relevant dietary antioxidants on redox biology. These include their antioxidant capacity that may affect biomarkers of oxidative stress and inflammation, as well as their role in the regulation of mitochondrial function, cell signaling proteins, ion channels and transporters, and the ubiquitination/proteasome system, preventing the occurrence of numerous pathological processes.

Prof. Dr. Nada Orsolic
Dr. Maja Jazvinšćak Jembrek
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

  • oxidants and free radical production
  • physiological activities of free radicals
  • detrimental effects of free radicals on human health
  • ROS and ROS-mediated cellular signaling
  • pathophysiology of oxidative stress
  • biomarkers of oxidative stress
  • chronic degenerative diseases
  • therapeutic approaches targeting oxidative stress
  • biochemical/molecular targets of chronic diseases
  • exogenous antioxidants and human health
  • flavonoids and redox biology in the pathophysiology of diseases
  • pro-oxidative role of antioxidants: double-sided sword
  • prooxidant agents in therapy

Published Papers (5 papers)

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Research

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12 pages, 2203 KiB  
Communication
Gene Expression and Prognostic Value of NADPH Oxidase Enzymes in Breast Cancer
by Andressa de Vasconcelos e Souza, Caroline Coelho de Faria, Leonardo Matta Pereira, Andrea Claudia Freitas Ferreira, Pedro Henrique Monteiro Torres and Rodrigo Soares Fortunato
Int. J. Mol. Sci. 2024, 25(6), 3464; https://doi.org/10.3390/ijms25063464 - 19 Mar 2024
Viewed by 557
Abstract
NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. [...] Read more.
NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. For this, mRNA expression from 290 normal breast tissue samples and 1904 BC samples obtained from studies on cBioPortal, Kaplan–Meier Plotter, and The Human Protein Atlas were analyzed. We found higher levels of NOX2, NOX4, and Dual oxidase 1 (DUOX1) in normal breast tissue. NOX1, NOX2, and NOX4 exhibited higher expression in BC, except for the basal subtype, where NOX4 expression was lower. DUOX1 mRNA levels were lower in all BC subtypes. NOX2, NOX4, and NOX5 mRNA levels increased with tumor progression stages, while NOX1 and DUOX1 expression decreased in more advanced stages. Moreover, patients with low expression of NOX1, NOX4, and DUOX1 had lower survival rates than those with high expression of these enzymes. In conclusion, our data suggest an overexpression of NOX enzymes in breast cancer, with certain isoforms showing a positive correlation with tumor progression. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease)
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20 pages, 12760 KiB  
Article
Hepatic Alterations in a BTBR T + Itpr3tf/J Mouse Model of Autism and Improvement Using Melatonin via Mitigation Oxidative Stress, Inflammation and Ferroptosis
by Rita Rezzani, Marzia Gianò, Daniela Pinto, Fabio Rinaldi, Cornelis J. F. van Noorden and Gaia Favero
Int. J. Mol. Sci. 2024, 25(2), 1086; https://doi.org/10.3390/ijms25021086 - 16 Jan 2024
Viewed by 859
Abstract
Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present [...] Read more.
Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease)
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Graphical abstract

9 pages, 1442 KiB  
Article
Comparative Analysis of Anticonvulsant Activity of Trans and Cis 5,5′-Diphenylhydantoin Schiff Bases
by Jana Tchekalarova, Petar Todorov, Tsveta Stoyanova and Milena Atanasova
Int. J. Mol. Sci. 2023, 24(22), 16071; https://doi.org/10.3390/ijms242216071 - 08 Nov 2023
Cited by 2 | Viewed by 700
Abstract
Recently, the four 5,5′-diphenylhydantoin Schiff bases, possessing different aromatic species (SB1-Ph, SB2-Ph, SB3-Ph and SB4-Ph) were synthesized, characterized, and evaluated for anticonvulsant activity in combination with phenytoin. In the present study, the SB1-Ph and SB4-Ph compounds were selected, based on their [...] Read more.
Recently, the four 5,5′-diphenylhydantoin Schiff bases, possessing different aromatic species (SB1-Ph, SB2-Ph, SB3-Ph and SB4-Ph) were synthesized, characterized, and evaluated for anticonvulsant activity in combination with phenytoin. In the present study, the SB1-Ph and SB4-Ph compounds were selected, based on their anticonvulsant potency, and compared with their cis isomers, prepared after a one-hour exposure to the UV source, for their anticonvulsant potency in the maximal electroshock (MES) test and the kainate (KA)-induced status epilepticus (SE) test in mice. In the MES test, the cis SB1-Ph compound exhibited superior to phenytoin and trans isomer activity in the three tested doses, while the cis SB4-Ph compound entirely suppressed the electroshock-induced seizure spread at the highest dose of 40 mg/kg. Pretreatment with the cis SB1-Ph compound and the cis SB4-Ph at the doses of 40 mg/kg, respectively, for seven days, significantly attenuated the severity of KA SE compared to the matched control group pretreated with a vehicle, while phenytoin was ineffective in this test. The cis SB4-Ph but not the cis SB1-Ph demonstrated an antioxidant effect against the KA-induced SE in the hippocampus. Our results suggest that trans–cis conversion of 5,5′-diphenylhydantoin Schiff bases has potential against seizure spread in the MES test and mitigated the KA-induced SE. The antioxidant potency of cis SB4-Ph might be associated with its efficacy in mitigating the SE. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease)
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Review

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41 pages, 3703 KiB  
Review
Antioxidant Enzymes in Cancer Cells: Their Role in Photodynamic Therapy Resistance and Potential as Targets for Improved Treatment Outcomes
by Wachirawit Udomsak, Malgorzata Kucinska, Julia Pospieszna, Hanna Dams-Kozlowska, Waranya Chatuphonprasert and Marek Murias
Int. J. Mol. Sci. 2024, 25(6), 3164; https://doi.org/10.3390/ijms25063164 - 09 Mar 2024
Viewed by 797
Abstract
Photodynamic therapy (PDT) is a selective tumor treatment that consists of a photosensitive compound—a photosensitizer (PS), oxygen, and visible light. Although each component has no cytotoxic properties, their simultaneous use initiates photodynamic reactions (PDRs) and sequentially generates reactive oxygen species (ROS) and/or free [...] Read more.
Photodynamic therapy (PDT) is a selective tumor treatment that consists of a photosensitive compound—a photosensitizer (PS), oxygen, and visible light. Although each component has no cytotoxic properties, their simultaneous use initiates photodynamic reactions (PDRs) and sequentially generates reactive oxygen species (ROS) and/or free radicals as cytotoxic mediators, leading to PDT-induced cell death. Nevertheless, tumor cells develop various cytoprotective mechanisms against PDT, particularly the adaptive mechanism of antioxidant status. This review integrates an in-depth analysis of the cytoprotective mechanism of detoxifying ROS enzymes that interfere with PDT-induced cell death, including superoxide dismutase (SOD), catalase, glutathione redox cycle, and heme oxygenase-1 (HO-1). Furthermore, this review includes the use of antioxidant enzymes inhibitors as a strategy in order to diminish the antioxidant activities of tumor cells and to improve the effectiveness of PDT. Conclusively, PDT is an effective tumor treatment of which its effectiveness can be improved when combined with a specific antioxidant inhibitor. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease)
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16 pages, 3234 KiB  
Review
Oxidative Mechanisms and Cardiovascular Abnormalities of Cirrhosis and Portal Hypertension
by Hongqun Liu, Henry H. Nguyen, Sang Youn Hwang and Samuel S. Lee
Int. J. Mol. Sci. 2023, 24(23), 16805; https://doi.org/10.3390/ijms242316805 - 27 Nov 2023
Viewed by 1002
Abstract
In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species [...] Read more.
In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species (ROS). ROS has been associated with intestinal mucosal injury, increased intestinal permeability, enhanced gut bacterial overgrowth, and translocation; all these changes result in increased endotoxin and inflammation. Portal hypertension also results in the development of collateral circulation and reduces liver mass resulting in an overall increase in endotoxin/bacteria bypassing detoxication and immune clearance in the liver. Endotoxemia can in turn aggravate oxidative stress and inflammation, leading to a cycle of gut barrier dysfunction → endotoxemia → organ injury. The phenotype of cardiovascular abnormalities includes hyperdynamic circulation and cirrhotic cardiomyopathy. Oxidative stress is often accompanied by inflammation; thus, blocking oxidative stress can minimize the systemic inflammatory response and alleviate the severity of cardiovascular diseases. The present review aims to elucidate the role of oxidative stress in cirrhosis-associated cardiovascular abnormalities and discusses possible therapeutic effects of antioxidants on cardiovascular complications of cirrhosis including hyperdynamic circulation, cirrhotic cardiomyopathy, and hepatorenal syndrome. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease)
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