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Redox Homeostasis and Oxidative Stress in Human Metabolism and Disease

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

Deadline for manuscript submissions: closed (20 October 2024) | Viewed by 10755

Special Issue Editors


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Guest Editor
Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland
Interests: reactive oxygen species; oxidative stress; antioxidants; lipid peroxidation; exercise biochemistry; cryostimulation; parasitology
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland
Interests: reactive oxygen species; oxidative stress; antioxidants; oncology; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The finely tuned equilibrium of redox reactions forms the bedrock of many cellular functions underlying key metabolic processes and influencing the health of tissues and organs. This balance, critical for cell functionality, is frequently compromised in a myriad of diseases, including metabolic disorders, degenerative conditions and various other pathophysiological states. Perturbations in redox homeostasis often result from an imbalance between the production of reactive oxygen species (ROS) and antioxidant response mechanisms. At physiological levels, ROS serve as pivotal signaling molecules in a wide range of metabolic activities. However, excessive ROS accumulation can deleteriously perturb metabolic functions, instigating a diseased state and accelerating its progression. Furthermore, the intimate relationship between redox dynamics and human metabolism becomes even more complex when considering the influence of exogenous factors. These agents, in varied concentrations, can either maintain a redox equilibrium, thereby aiding metabolic function, or disrupt it, exacerbating oxidative stress. A deeper grasp of these multifaceted interactions is crucial not only for understanding disease etiology, but also devising innovative therapeutic interventions and preventive measures.

In this vein, this Special Issue invites submissions of original research articles that shed light on the intricate dance of redox signaling within metabolic contexts, both in health and disease. Articles highlighting the potential therapeutic strategies targeting redox imbalances in metabolic disorders are particularly encouraged. Additionally, comprehensive review articles that evaluate and dissect the current knowledge landscape pertaining to the theme are most welcome.

Prof. Dr. Alina Woźniak
Dr. Jaroslaw Nuszkiewicz
Guest Editors

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Keywords

  • antioxidants
  • biomarkers
  • cellular functions
  • disease etiology
  • disease progression
  • metabolic disorders
  • metabolic signaling
  • oxidative stress
  • pathophysiological states
  • reactive oxygen species
  • redox homeostasis
  • redox signaling

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Published Papers (9 papers)

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Research

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19 pages, 1367 KiB  
Article
Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells
by Elena Grossini, Carmen Imma Aquino, Sakthipriyan Venkatesan, Libera Troìa, Eleonora Tizzoni, Federica Fumagalli, Daniela Ferrante, Rosanna Vaschetto, Valentino Remorgida and Daniela Surico
Int. J. Mol. Sci. 2024, 25(9), 4869; https://doi.org/10.3390/ijms25094869 - 29 Apr 2024
Cited by 2 | Viewed by 890
Abstract
Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical [...] Read more.
Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy. Full article
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13 pages, 2792 KiB  
Communication
Oxidative Stress Markers and Histopathological Changes in Selected Organs of Mice Infected with Murine Norovirus 1 (MNV-1)
by Paulina Janicka, Dominika Stygar, Elżbieta Chełmecka, Piotr Kuropka, Arkadiusz Miążek, Aleksandra Studzińska, Aleksandra Pogorzelska, Katarzyna Pala and Barbara Bażanów
Int. J. Mol. Sci. 2024, 25(7), 3614; https://doi.org/10.3390/ijms25073614 - 23 Mar 2024
Viewed by 1098
Abstract
This paper describes the effects of murine norovirus (MNV) infection on oxidative stress and histopathological changes in mice. This study uses histopathological assays, enzymatic and non-enzymatic antioxidant markers, and total oxidative status and capacity (TOS, TAC). The results suggest that MNV infection can [...] Read more.
This paper describes the effects of murine norovirus (MNV) infection on oxidative stress and histopathological changes in mice. This study uses histopathological assays, enzymatic and non-enzymatic antioxidant markers, and total oxidative status and capacity (TOS, TAC). The results suggest that MNV infection can lead to significant changes with respect to the above-mentioned parameters in various organs. Specifically, reduced superoxide dismutase (SOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione reductase (GR) activities were observed in liver tissues, while higher MnSOD activity was observed in kidney tissues of MNV-infected mice when compared to the control. GR activity was lower in all tissues of MNV-infected mice tested, with the exception of lung tissue. This study also showed that norovirus infection led to increased TOS levels in the brain and liver and TAC levels in the brain, while TOS levels were significantly reduced in the kidneys. These changes may be due to the production of reactive oxygen species (ROS) caused by the viral infection. ROS can damage cells and contribute to oxidative stress. These studies help us to understand the pathogenesis of MNV infection and its potential effects on oxidative stress and histopathological changes in mice, and pave the way for further studies of the long-term effects of MNV infection. Full article
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16 pages, 986 KiB  
Article
Preliminary Report on the Influence of Acute Inflammation on Adiponectin Levels in Older Inpatients with Different Nutritional Status
by Jakub Husejko, Marcin Gackowski, Jakub Wojtasik, Dominika Strzała, Maciej Pesta, Katarzyna Mądra-Gackowska, Jarosław Nuszkiewicz, Alina Woźniak, Mariusz Kozakiewicz and Kornelia Kędziora-Kornatowska
Int. J. Mol. Sci. 2024, 25(4), 2016; https://doi.org/10.3390/ijms25042016 - 7 Feb 2024
Cited by 1 | Viewed by 1092
Abstract
Inflammation can be triggered by a variety of factors, including pathogens, damaged cells, and toxic compounds. It is a biological response of the immune system, which can be successfully assessed in clinical practice using some molecular substances. Because adiponectin, a hormone released by [...] Read more.
Inflammation can be triggered by a variety of factors, including pathogens, damaged cells, and toxic compounds. It is a biological response of the immune system, which can be successfully assessed in clinical practice using some molecular substances. Because adiponectin, a hormone released by adipose tissue, influences the development of inflammation, its evaluation as a potential measure of inflammation in clinical practice is justified. In the present contribution, statistical comparison of adiponectin concentration and selected molecular substances recognized in clinical practice as measures of inflammation were utilized to demonstrate whether adipose tissue hormones, as exemplified by adiponectin, have the potential to act as a measure of rapidly changing inflammation when monitoring older hospitalized patients in the course of bacterial infection. The study showed no statistically significant differences in adiponectin levels depending on the rapidly changing inflammatory response in its early stage. Interestingly, the concentration of adiponectin is statistically significantly higher in malnourished patients than in people with normal nutritional levels, assessed based on the MNA. According to the results obtained, adiponectin is not an effective measure of acute inflammation in clinical practice. However, it may serve as a biomarker of malnutrition in senile individuals. Full article
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Review

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15 pages, 723 KiB  
Review
The Role of Selected Elements in Oxidative Stress Protection: Key to Healthy Fertility and Reproduction
by Marcin Wróblewski, Weronika Wróblewska and Marta Sobiesiak
Int. J. Mol. Sci. 2024, 25(17), 9409; https://doi.org/10.3390/ijms25179409 - 29 Aug 2024
Viewed by 850
Abstract
Oxidative stress and its relationship to fertility and reproduction is a topic of interest in medicine, especially in the context of the effects of trace elements and micronutrients. Oxidative stress occurs when there is an excess of free radicals in the body, which [...] Read more.
Oxidative stress and its relationship to fertility and reproduction is a topic of interest in medicine, especially in the context of the effects of trace elements and micronutrients. Oxidative stress occurs when there is an excess of free radicals in the body, which can lead to cell and tissue damage. Free radicals are reactive oxygen species (ROS) that can be formed as a result of normal metabolic processes, as well as under the influence of external factors such as environmental pollution, UV radiation, and diet. Oxidative stress has a significant impact on fertility. In men, it can lead to DNA damage in sperm, which can result in reduced semen quality, reduced sperm motility and increased numbers of defective sperm, and free radical damage to sperm cell membranes causing a reduction in the number of available sperm. In women, oxidative stress can affect the quality of female reproductive cells, which can lead to problems with their maturation and with embryo implantation in the uterus and can also affect ovarian function and disrupt hormonal regulation of the menstrual cycle. A proper balance of trace elements and micronutrients is key to protecting against oxidative stress and maintaining reproductive health. Supplementation with appropriate elements such as zinc, selenium, copper, manganese, chromium, and iron can help reduce oxidative stress and improve fertility. This work discusses the effects of selected elements on oxidative stress parameters specifically in terms of fertility and reproduction. Full article
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29 pages, 1154 KiB  
Review
Environmental and Genetic Determinants of Ankylosing Spondylitis
by Rafał Bilski, Piotr Kamiński, Daria Kupczyk, Sławomir Jeka, Jędrzej Baszyński, Halina Tkaczenko and Natalia Kurhaluk
Int. J. Mol. Sci. 2024, 25(14), 7814; https://doi.org/10.3390/ijms25147814 - 17 Jul 2024
Cited by 1 | Viewed by 1492
Abstract
Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some [...] Read more.
Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some researchers are looking for more genetic factors underlying AS, most studies focus on polymorphisms within the genes encoding the human leukocyte antigen (HLA) system. The biggest challenge is finding the effective treatment of the disease. Genetic factors and the influence of oxidative stress, mineral metabolism disorders, microbiota, and tobacco smoking seem to be of great importance for the development of AS. The data contained in this review constitute valuable information and encourage the initiation and development of research in this area, showing connections between inflammatory disorders leading to the pathogenesis of AS and selected environmental and genetic factors. Full article
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16 pages, 799 KiB  
Review
The Current State of Knowledge Regarding the Genetic Predisposition to Sports and Its Health Implications in the Context of the Redox Balance, Especially Antioxidant Capacity
by Paweł Sutkowy, Martyna Modrzejewska, Marta Porzych and Alina Woźniak
Int. J. Mol. Sci. 2024, 25(13), 6915; https://doi.org/10.3390/ijms25136915 - 24 Jun 2024
Viewed by 786
Abstract
The significance of physical activity in sports is self-evident. However, its importance is becoming increasingly apparent in the context of public health. The constant desire to improve health and performance suggests looking at genetic predispositions. The knowledge of genes related to physical performance [...] Read more.
The significance of physical activity in sports is self-evident. However, its importance is becoming increasingly apparent in the context of public health. The constant desire to improve health and performance suggests looking at genetic predispositions. The knowledge of genes related to physical performance can be utilized initially in the training of athletes to assign them to the appropriate sport. In the field of medicine, this knowledge may be more effectively utilized in the prevention and treatment of cardiometabolic diseases. Physical exertion engages the entire organism, and at a basic physiological level, the organism’s responses are primarily related to oxidant and antioxidant reactions due to intensified cellular respiration. Therefore, the modifications involve the body adjusting to the stresses, especially oxidative stress. The consequence of regular exercise is primarily an increase in antioxidant capacity. Among the genes considered, those that promote oxidative processes dominate, as they are associated with energy production during exercise. What is missing, however, is a look at the other side of the coin, which, in this case, is antioxidant processes and the genes associated with them. It has been demonstrated that antioxidant genes associated with increased physical performance do not always result in increased antioxidant capacity. Nevertheless, it seems that maintaining the oxidant–antioxidant balance is the most important thing in this regard. Full article
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36 pages, 2067 KiB  
Review
Immunogenetic and Environmental Factors in Age-Related Macular Disease
by Sylwia Brodzka, Jędrzej Baszyński, Katarzyna Rektor, Karolina Hołderna-Bona, Emilia Stanek, Natalia Kurhaluk, Halina Tkaczenko, Grażyna Malukiewicz, Alina Woźniak and Piotr Kamiński
Int. J. Mol. Sci. 2024, 25(12), 6567; https://doi.org/10.3390/ijms25126567 - 14 Jun 2024
Cited by 1 | Viewed by 915
Abstract
Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other [...] Read more.
Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment. Full article
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21 pages, 3463 KiB  
Review
Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling
by Karsten Gülow, Deniz Tümen, Philipp Heumann, Stephan Schmid, Arne Kandulski, Martina Müller and Claudia Kunst
Int. J. Mol. Sci. 2024, 25(11), 6114; https://doi.org/10.3390/ijms25116114 - 1 Jun 2024
Cited by 3 | Viewed by 1046
Abstract
Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I [...] Read more.
Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I and III of the electron transport chain (ETC). Subsequent ROS production triggers the activation of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2), prolonging the oxidative signal. This signal then engages kinase signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway and increases the activity of REDOX-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). To limit ROS overproduction and prevent oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant proteins such as superoxide dismutases (SODs) finely regulate signal intensity and are capable of terminating the oxidative signal when needed. Thus, oxidative signals, such as T cell activation, are well-controlled and critical for cellular communication. Full article
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16 pages, 2981 KiB  
Review
The Role of Glutathione in Age-Related Macular Degeneration (AMD)
by Sylwia Brodzka, Jędrzej Baszyński, Katarzyna Rektor, Karolina Hołderna-Bona, Emilia Stanek, Natalia Kurhaluk, Halina Tkaczenko, Grażyna Malukiewicz, Alina Woźniak and Piotr Kamiński
Int. J. Mol. Sci. 2024, 25(8), 4158; https://doi.org/10.3390/ijms25084158 - 9 Apr 2024
Cited by 4 | Viewed by 1630
Abstract
Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The [...] Read more.
Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet—progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye. Full article
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