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Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism

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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 (1 October 2023) | Viewed by 21021

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Special Issue Editor

Dr. Slađan Pavlović

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Guest Editor

Institute for Biological Research “Siniša Stanković”-National Institute of the Republic of Serbia, Belgrade, Serbia
Interests: redox physiology; antioxidative defense system; animal and human physiology; general and biomedical ecophysiology; metallomics; pathophysiology; toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to participate in a Special Issue of MDPI´s International Journal of Molecular Sciences (ISSN 1422-0067) entitled: “Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism”. It became clear that the modulation of the redox status can be the cause of many pathophysiological conditions in animals and humans. This is why this Special Issue covers a wide range of biomedical research with a special emphasis on results at the molecular level. We encourage authors to submit their manuscripts relating to: the impact of redox-active pollutants on the reproductive health of women and men; the connection between redox regulation of cellular redox status in COVID-19/post-COVID-19 patients; reactive species in redox signaling; redox-active natural products in diabetes; toxic trace elements in placental tissue, umbilical cord, and maternal blood in pregnant women with physiological pregnancies; influence of various xenobiotics on cellular redox status in aquatic organisms; and the influence of redox-active trace metals in physiological processes in normal and pathophysiological conditions.

Both Original research papers and Review articles are welcome.

Dr. Sladjan Z. Pavlović
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. 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

redox-signalling pathways
Antioxidative and hypoglicemic effects of plant extracts
prooxidant/antioxidant status in the cells
redox active trace metals
reproductive health of women and men: infertility/sterility
xenobiotics in aquatic organims
essential trace elements and immunological parameters in COVID/post-COVID patients

Related Special Issue

Redox Physiology in Biomedicine and Ecophysiology: The Influence of Various Substances on the Redox Regulation of Cell Metabolism, 2nd Edition in International Journal of Molecular Sciences (1 article)

Published Papers (8 papers)

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Research

18 pages, 4464 KiB

Open AccessArticle

Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo

by Betul Cicek, Betul Danısman, Serkan Yildirim, Neslihan Yuce, Dragana Nikitovic, Ismail Bolat, Mehmet Kuzucu, Ertuğrul Ceyran, Ebru Bardas, Kirill S. Golokhvast, Aristidis Tsatsakis and Ali Taghizadehghalehjoughi

Int. J. Mol. Sci. 2023, 24(20), 15486; https://doi.org/10.3390/ijms242015486 - 23 Oct 2023

Cited by 2 | Viewed by 1231

Abstract

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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12 pages, 286 KiB

Open AccessArticle

Redox Status and Telomere–Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

by Aleksandra Vukašinović, Aleksandra Klisic, Barbara Ostanek, Srdjan Kafedžić, Marija Zdravković, Ivan Ilić, Miron Sopić, Saša Hinić, Milica Stefanović, Nataša Bogavac-Stanojević, Janja Marc, Aleksandar N. Nešković and Jelena Kotur-Stevuljević

Int. J. Mol. Sci. 2023, 24(18), 14308; https://doi.org/10.3390/ijms241814308 - 20 Sep 2023

Cited by 1 | Viewed by 889

Abstract

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O₂^•−), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere–telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The “cholesterol–protein factor” and “oxidative–telomere factor” were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the “oxidative–telomere factor” (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

13 pages, 1865 KiB

Open AccessArticle

Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization

by Renata Mangione, Romina Pallisco, Gabriele Bilotta, Francesca Marroni, Valentina Di Pietro, Elena Capoccia, Giuseppe Lazzarino, Barbara Tavazzi, Giacomo Lazzarino, Pasquale Bilotta and Angela Maria Amorini

Int. J. Mol. Sci. 2023, 24(13), 10707; https://doi.org/10.3390/ijms241310707 - 27 Jun 2023

Cited by 1 | Viewed by 1350

Abstract

In a previous study, we showed that various low-molecular-weight compounds in follicular fluid (FF) samples of control fertile females (CFF) have different concentrations compared to those found in FF of infertile females (IF), before and after their categorization into different subgroups, according to their clinical diagnosis of infertility. Using the same FF samples of this previous study, we here analyzed the FF concentrations of free and bound bilirubin and compared the results obtained in CFF, IF and the different subgroups of IF (endometriosis, EM, polycystic ovary syndrome, PCOS, age-related reduced ovarian reserve, AR-ROR, reduced ovarian reserve, ROR, genetic infertility, GI and unexplained infertility, UI). The results clearly indicated that CFF had lower values of free, bound and total bilirubin compared to the respective values measured in pooled IF. These differences were observed even when IF were categorized into EM, PCOS, AR-ROR, ROR, GI and UI, with EM and PCOS showing the highest values of free, bound and total bilirubin among the six subgroups. Using previous results of ascorbic acid, GSH and nitrite + nitrate measured in the same FF samples of the same FF donors, we found that total bilirubin in FF increased as a function of decreased values of ascorbic acid and GSH, and increased concentrations of nitrite + nitrate. The values of total bilirubin negatively correlated with the clinical parameters of fertilization procedures (number of retrieved oocytes, mature oocytes, fertilized oocytes, blastocysts, high-quality blastocysts) and with clinical pregnancies and birth rates. Bilirubin concentrations in FF were not linked to those found in serum samples of FF donors, thereby strongly suggesting that its over production was due to higher activity of heme oxygenase-1 (HO-1), the key enzyme responsible for bilirubin formation, in granulosa cells, or cumulus cells or oocytes of IF and ultimately leading to bilirubin accumulation in FF. Since increased activity of HO-1 is one of the main enzymatic intracellular mechanisms of defense towards external insults (oxidative/nitrosative stress, inflammation), and since we found correlations among bilirubin and oxidative/nitrosative stress in these FF samples, it may reasonably be supposed that bilirubin increase in FF of IF is the result of protracted exposures to the aforementioned insults evidently playing relevant roles in female infertility. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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14 pages, 5237 KiB

Open AccessArticle

Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta

by Svetlana Trifunović, Branka Šošić Jurjević, Nataša Ristić, Nataša Nestorović, Branko Filipović, Ivana Stevanović, Vesna Begović-Kuprešanin and Milica Manojlović-Stojanoski

Int. J. Mol. Sci. 2023, 24(1), 540; https://doi.org/10.3390/ijms24010540 - 29 Dec 2022

Cited by 2 | Viewed by 8428

Abstract

As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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12 pages, 2833 KiB

Open AccessArticle

Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis

by Aleksandra Nikolić-Kokić, Nikola Tatalović, Jelena Brkljačić, Milica Mijović, Vojkan Nestorović, Ana Mijušković, Zorana Oreščanin-Dušić, Teodora Vidonja Uzelac, Milan Nikolić, Snežana Spasić, Duško Blagojević and Čedo Miljević

Int. J. Mol. Sci. 2022, 23(22), 13698; https://doi.org/10.3390/ijms232213698 - 8 Nov 2022

Viewed by 1898

Abstract

Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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22 pages, 2244 KiB

Open AccessArticle

The Effects of BSA-Stabilized Selenium Nanoparticles and Sodium Selenite Supplementation on the Structure, Oxidative Stress Parameters and Selenium Redox Biology in Rat Placenta

by Milica Manojlović-Stojanoski, Slavica Borković-Mitić, Nataša Nestorović, Nataša Ristić, Svetlana Trifunović, Magdalena Stevanović, Nenad Filipović, Aleksandar Stojsavljević and Slađan Pavlović

Int. J. Mol. Sci. 2022, 23(21), 13068; https://doi.org/10.3390/ijms232113068 - 28 Oct 2022

Cited by 4 | Viewed by 1897

Abstract

The chemical element selenium (Se) is a nonmetal that is in trace amounts indispensable for normal cellular functioning. During pregnancy, a low Se status can increase the risk of oxidative stress. However, elevated concentrations of Se in the body can also cause oxidative stress. This study aimed to compare the effects of BSA-stabilized Se nanoparticles (SeNPs, Se⁰) (BSA-bovine serum albumin) and inorganic sodium selenite (NaSe, Se⁺⁴) supplementation on the histological structure of the placenta, oxidative stress parameters and the total placental Se concentration of Wistar rats during pregnancy. Pregnant females were randomized into four groups: (i) intact controls; (ii) controls that were dosed by daily oral gavage with 8.6% bovine serum albumin (BSA) and 0.125 M vit C; (iii) the SeNP group that was administered 0.5 mg of SeNPs stabilized with 8.6% BSA and 0.125 M vit C/kg bw/day by oral gavage dosing; (iv) the NaSe group, gavage dosed with 0.5 mg Na₂SeO₃/kg bw/day. The treatment of pregnant females started on gestational day one, lasted until day 20, and on day 21 of gestation, the fetuses with the placenta were removed from the uterus. Our findings show that the mode of action of equivalent concentrations of Se in SeNPs and NaSe depended on its redox state and chemical structure. Administration of SeNPs (Se⁰) increased fetal lethality and induced changes in the antioxidative defense parameters in the placenta. The accumulation of Se in the placenta was highest in SeNP-treated animals. All obtained data indicate an increased bioavailability of Se in its organic nano form and Se⁰ redox state in comparison to its inorganic sodium selenite form and Se⁺⁴ redox state. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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14 pages, 1263 KiB

Open AccessArticle

Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function

by Danica Tasić, Miloš Opačić, Sanja Kovačević, Aleksandra Nikolić Kokić, Milena Dimitrijević, Dušan Nikolić, Danijela Vojnović Milutinović, Duško Blagojević, Ana Djordjevic and Jelena Brkljačić

Int. J. Mol. Sci. 2022, 23(16), 9023; https://doi.org/10.3390/ijms23169023 - 12 Aug 2022

Cited by 3 | Viewed by 1836

Abstract

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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12 pages, 836 KiB

Open AccessArticle

Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy

by Jovana Jagodić, Slađan Pavlović, Slavica Borković-Mitić, Milan Perović, Željko Miković, Slađana Đurđić, Dragan Manojlović and Aleksandar Stojsavljević

Int. J. Mol. Sci. 2022, 23(15), 8078; https://doi.org/10.3390/ijms23158078 - 22 Jul 2022

Cited by 8 | Viewed by 1849

Abstract

With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses. Full article

(This article belongs to the Special Issue Redox Physiology in Biomedicine and Ecophysology: Influence of Various Substances in Redox Regulation of Cell Metabolism)

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