Submit to Antioxidants Review for Antioxidants Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 25493

Share This Special Issue

Special Issue Editors

Dr. Małgorzata B. Iciek

E-Mail Website
Guest Editor

The Chair of Medical Biochemistry, Jagiellonian University Medical College, 31-008 Krakow, Poland
Interests: sulfane sulfur; hydrogen sulfide; sulfurtransferases; glutathione; thiol redox regulation; S-sulfhydration
Special Issues, Collections and Topics in MDPI journals

Dr. Anna Bilska-Wilkosz

E-Mail Website
Guest Editor

Department of Medical Biochemistry, Jagiellonian University Medical College, 31-008 Krakow, Poland
Interests: sulfane sulfur; hydrogen sulfide; sulfurtransferases; oxidoreductases; metabolism of amino acids; biochemistry and pharmacology of lipoic acid
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reactive sulfur species (RSS) have been recognized as molecules playing an important role in redox signaling just like the well-known reactive oxygen (ROS) and nitrogen (RNS) species. This year marks 20 years since the term RSS was introduced, and although this topic is developing very dynamically and has been the focus of thematic sessions at large biochemical conferences, the concept of RSS is little known for many scientists working in other fields.

The most biologically important RSS include hydrogen sulfide (H₂S) and compounds containing sulfane sulfur, i.e., thiosulfate, inorganic and organic polysulfides, low molecular weight persulfides (i.e., GSSH, CSSH), and protein persulfides. H₂S was the first to be recognized as a signaling molecule, and then some years later, persulfides/polysulfides were revealed to be responsible for many biological actions.

Recent discoveries characterize RSS as key players in redox regulation as important as ROS. We know a great deal about the synthesis and catabolism of H₂S and sulfane sulfur-containing compounds; however their biological role is still the subject of ongoing studies. It is especially important because disruption of RSS homeostasis may be implicated in many disorders, including cardiovascular diseases, cancer, immune system disturbances, metabolic syndrome, neurological deficits, and numerous others. In this context, studies aimed at searching for RSS donors which can be used to treat these pathologies are in progress.

In this Special Issue, we welcome original research papers as well as review articles dedicated to the biological role of RSS, the involvement of RSS disorders in pathological conditions, and therapeutic opportunities of RSS and their precursors. Papers based on human, animal, or cell studies can be published; new analytical methods for the detection of discrete pools of RSS in biological samples are also acceptable.

We look forward to receiving your contributions.

Dr. Małgorzata B. Iciek
Dr. Anna Bilska-Wilkosz
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. 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

reactive sulfur species
sulfane sulfur
hydrogen sulfide
persulfidation
thiol redox regulation
sulfane sulfur donors
sulfur metabolism
thiols
polysulfides

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

7 pages, 231 KiB

Open AccessEditorial

Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy

by Anna Bilska-Wilkosz and Małgorzata Iciek

Antioxidants 2022, 11(8), 1576; https://doi.org/10.3390/antiox11081576 - 15 Aug 2022

Cited by 2 | Viewed by 1349

Abstract

Sulfur is a multivalent and nonmetallic chemical element with the symbol S and the atomic number 16 [...] Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

Research

Jump to: Editorial, Review

14 pages, 1963 KiB

Open AccessArticle

Hydropersulfides (RSSH) Outperform Post-Conditioning and Other Reactive Sulfur Species in Limiting Ischemia–Reperfusion Injury in the Isolated Mouse Heart

by Blaze M. Pharoah, Vinayak S. Khodade, Alexander Eremiev, Eric Bao, Ting Liu, Brian O’Rourke, Nazareno Paolocci and John P. Toscano

Antioxidants 2022, 11(5), 1010; https://doi.org/10.3390/antiox11051010 - 20 May 2022

Cited by 14 | Viewed by 2562

Abstract

Hydrogen sulfide (H₂S) exhibits protective effects in cardiovascular disease such as myocardial ischemia/reperfusion (I/R) injury, cardiac hypertrophy, and atherosclerosis. Despite these findings, its mechanism of action remains elusive. Recent studies suggest that H₂S can modulate protein activity through redox-based post-translational modifications of protein cysteine residues forming hydropersulfides (RSSH). Furthermore, emerging evidence indicates that reactive sulfur species, including RSSH and polysulfides, exhibit cardioprotective action. However, it is not clear yet whether there are any pharmacological differences in the use of H₂S vs. RSSH and/or polysulfides. This study aims to examine the differing cardioprotective effects of distinct reactive sulfur species (RSS) such as H₂S, RSSH, and dialkyl trisulfides (RSSSR) compared with canonical ischemic post-conditioning in the context of a Langendorff ex-vivo myocardial I/R injury model. For the first time, a side-by-side study has revealed that exogenous RSSH donation is a superior approach to maintain post-ischemic function and limit infarct size when compared with other RSS and mechanical post-conditioning. Our results also suggest that RSSH preserves mitochondrial respiration in H9c2 cardiomyocytes exposed to hypoxia-reoxygenation via inhibition of oxidative phosphorylation while preserving cell viability. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

18 pages, 1870 KiB

Open AccessArticle

Optimization of a Monobromobimane (MBB) Derivatization and RP-HPLC-FLD Detection Method for Sulfur Species Measurement in Human Serum after Sulfur Inhalation Treatment

by Barbara Roda, Nan Zhang, Laura Gambari, Brunella Grigolo, Cristina Eller-Vainicher, Luigi Gennari, Alessandro Zappi, Stefano Giordani, Valentina Marassi, Andrea Zattoni, Pierluigi Reschiglian and Francesco Grassi

Antioxidants 2022, 11(5), 939; https://doi.org/10.3390/antiox11050939 - 10 May 2022

Cited by 11 | Viewed by 2254

Abstract

(1) Background: Hydrogen sulfide (H₂S) is a widely recognized gasotransmitter, with key roles in physiological and pathological processes. The accurate quantification of H₂S and reactive sulfur species (RSS) may hold important implications for the diagnosis and prognosis of diseases. However, H₂S species quantification in biological matrices is still a challenge. Among the sulfide detection methods, monobromobimane (MBB) derivatization coupled with reversed phase high-performance liquid chromatography (RP-HPLC) is one of the most reported. However, it is characterized by a complex preparation and time-consuming process, which may alter the actual H₂S level; moreover, a quantitative validation has still not been described. (2) Methods: We developed and validated an improved analytical protocol for the MBB RP-HPLC method. MBB concentration, temperature and sample handling were optimized, and the calibration method was validated using leave-one-out cross-validation and tested in a clinical setting. (3) Results: The method shows high sensitivity and allows the quantification of H₂S species, with a limit of detection of 0.5 µM. Finally, it can be successfully applied in measurements of H₂S levels in the serum of patients subjected to inhalation with vapors rich in H₂S. (4) Conclusions: These data demonstrate that the proposed method is precise and reliable for measuring H₂S species in biological matrices and can be used to provide key insights into the etiopathogenesis of several diseases and sulfur-based treatments. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

15 pages, 2176 KiB

Open AccessArticle

Effect of Alpha-Lipoic Acid on Rat Ventricles and Atria under LPS-Induced Oxidative Stress

by Beata Skibska, Anna Goraca, Agnieszka Skibska and Andrzej Stanczak

Antioxidants 2022, 11(4), 734; https://doi.org/10.3390/antiox11040734 - 08 Apr 2022

Cited by 10 | Viewed by 2130

Abstract

Alpha-lipoic acid (α-LA) is a disulfide compound and one of the most effective antioxidants. Many studies have indicated positive effects of α-LA in the prevention of pathologic conditions mediated by oxidative stress, such as cardiovascular diseases. However, the therapeutic potential of α-LA for the heart has not been explored with regards to the ventricles and atria. The aim of our study was to evaluate the effects of α-LA on oxidative stress parameters and inflammation in the ventricles and atria of the heart in rats under LPS-induced oxidative stress. Wistar rats were divided into 4 groups: I—control (received 2 doses of 0.2 mL of 0.9% NaCl i.v., 0.5 h apart); II—α-LA (received 0.2 mL of 0.9% NaCl and 0.5 h later received α-LA 60 mg/kg b.w. i.v.); III—lipopolysaccharide (LPS) (received 0.2 mL of 0.9% NaCl and 0.5 h later received LPS 30 mg/kg b.w. i.v.); and IV—LPS + LA (received LPS 30 mg/kg b.w. i.v. and 0.5 h later received α-LA 60 mg/kg b.w. i.v.). Five hours later, the rats were euthanized. The hearts were surgically removed and weighed to estimate heart edema. The ventricular and atrium tissue was isolated to measure levels of TNF-α, IL-6, superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H₂O₂), total sulfhydryl groups (-SH), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulfide (GSSG), and the GSH/GSSG ratio. LPS significantly increased TNF-α, IL-6, TBARS, and H₂O₂ levels and decreased SOD, -SH groups, tGSH, the GSH/GSSG ratio, and GSH levels in rat ventricles and atria while α-LA administered after the injection of LPS significantly decreased TNF-α, IL-6, TBARS, and H₂O₂ levels. α-LA also increased SOD and -SH group levels and ameliorated the glutathione redox status when compared to the LPS group. Our data suggest that α-LA administration 30 min after LPS infusion may effectively prevent inflammation and oxidative stress in the ventricles and atria. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

12 pages, 1326 KiB

Open AccessArticle

Airway Thiol-NO Adducts as Determinants of Exhaled NO

by Megan Pophal, Zachary W. Grimmett, Clara Chu, Seunghee Margevicius, Thomas Raffay, Kristie Ross, Anjum Jafri, Olivia Giddings, Jonathan S. Stamler, Benjamin Gaston and James D. Reynolds

Antioxidants 2021, 10(10), 1527; https://doi.org/10.3390/antiox10101527 - 26 Sep 2021

Cited by 2 | Viewed by 1685

Abstract

Thiol-NO adducts such as S-nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway S-nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (F_ENO) is associated with asthmatic airway inflammation. We hypothesized that F_ENO could reflect airway S-nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway S-nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary S-nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase ^−/−) unable reductively to catabolize GSNO. More NO was produced from GSNO in the ^−/− compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases F_ENO using an inhalational challenge model in normal human subjects. F_ENO increased in all subjects tested, with a median t_1/2 of 32.0 min. Taken together, these data demonstrate that F_ENO reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, F_ENO following a GSNO challenge could be a non-invasive test for airway GSNO catabolism. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

15 pages, 2651 KiB

Open AccessArticle

Saccharomyces cerevisiae Rhodanese RDL2 Uses the Arg Residue of the Active-Site Loop for Thiosulfate Decomposition

by Qingda Wang, Huanjie Li, Yongzhen Xia, Luying Xun and Huaiwei Liu

Antioxidants 2021, 10(10), 1525; https://doi.org/10.3390/antiox10101525 - 26 Sep 2021

Cited by 2 | Viewed by 1647

Abstract

Persulfide, polysulfide and thiosulfate are examples of sulfane sulfur containing chemicals that play multiple functions in biological systems. Rhodaneses are widely present in all three kingdoms of life, which catalyze sulfur transfer among these sulfane sulfur-containing chemicals. The mechanism of how rhodaneses function is not well understood. Saccharomyces cerevisiae rhodanese 2 (RDL2) is involved in mitochondrial biogenesis and cell cycle control. Herein, we report a 2.47 Å resolution structure of RDL2 co-crystallized with thiosulfate (PDB entry: 6K6R). The presence of an extra sulfur atom S_δ, forming a persulfide bond with the S_γ atom of Cys₁₀₆, was observed. Distinct from the persulfide groups in GlpE (PDB entry:1GMX) and rhobov (PDB entry:1BOI), the persulfide group of RDL2 is located in a peanut-like pocket of the neutral electrostatic field and is far away from positively charged amino acid residues of its active-site loop, suggesting no interaction between them. This finding suggests that the positively charged amino acid residues are not involved in the stabilization of the persulfide group. Activity assays indicate that the Arg₁₁₁ of the active-site loop is critical for the sulfane sulfur transfer. In vitro assays indicate that Arg propels the thiosulfate decomposition. Thus, we propose that Arg can offer a hydrogen bond-rich, acidic-like microenvironment in RDL2 in which thiosulfate decomposes to release sulfane sulfur. Thr of the active-site loop of rhodaneses has the same functions as Arg. Our proposal may explain the catalyzing mechanism of rhodaneses. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

28 pages, 3415 KiB

Open AccessReview

Reactive Sulfur Compounds in the Fight against COVID-19

by Małgorzata Iciek, Anna Bilska-Wilkosz, Michał Kozdrowicki and Magdalena Górny

Antioxidants 2022, 11(6), 1053; https://doi.org/10.3390/antiox11061053 - 26 May 2022

Cited by 12 | Viewed by 3900

Abstract

The SARS-CoV-2 coronavirus pandemic outbreak in 2019 resulted in the need to search for an effective and safe strategy for treating infected patients, relieving symptoms, and preventing severe disease. SARS-CoV-2 is an RNA virus that can cause acute respiratory failure and thrombosis, as well as impair circulatory system function. Permanent damage to the heart muscle or other cardiovascular disorders may occur during or after the infection. The severe course of the disease is associated with the release of large amounts of pro-inflammatory cytokines. Due to their documented anti-inflammatory, antioxidant, and antiviral effects, reactive sulfur compounds, including hydrogen sulfide (H₂S), lipoic acid (LA), N-acetylcysteine (NAC), glutathione (GSH), and some other lesser-known sulfur compounds, have attracted the interest of scientists for the treatment and prevention of the adverse effects of diseases caused by SARS-CoV-2. This article reviews current knowledge about various endogenous or exogenous reactive sulfur compounds and discusses the possibility, or in some cases the results, of their use in the treatment or prophylaxis of COVID-19. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

17 pages, 2223 KiB

Open AccessReview

A Whiff of Sulfur: One Wind a Day Keeps the Doctor Away

by Eduard Tiganescu, Markus Alexander Lämmermann, Yannick Ney, Ahmad Yaman Abdin, Muhammad Jawad Nasim and Claus Jacob

Antioxidants 2022, 11(6), 1036; https://doi.org/10.3390/antiox11061036 - 24 May 2022

Cited by 1 | Viewed by 2669

Abstract

Reactive Sulfur Species (RSS), such as allicin from garlic or sulforaphane from broccoli, are fre-quently associated with biological activities and possible health benefits in animals and humans. Among these Organic Sulfur Compounds (OSCs) found in many plants and fungi, the Volatile Sulfur Compounds (VSCs) feature prominently, not only because of their often-pungent smell, but also because they are able to access places which solids and solutions cannot reach that easily. Indeed, inorganic RSS such as hydrogen sulfide (H₂S) and sulfur dioxide (SO₂) can be used to lit-erally fumigate entire rooms and areas. Similarly, metabolites of garlic, such as allyl methyl sulfide (AMS), are formed metabolically in humans in lower concentrations and reach the airways from inside the body as part of one’s breath. Curiously, H₂S is also formed in the gastrointestinal tract by gut bacteria, and the question of if and for which purpose this gas then crosses the barriers and enters the body is indeed a delicate matter for equally delicate studies. In any case, nature is surprisingly rich in such VSCs, as fruits (for instance, the infamous durian) demonstrate, and therefore these VSCs represent a promising group of compounds for further studies. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

14 pages, 1151 KiB

Open AccessReview

Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge

by Bernd Moosmann and Parvana Hajieva

Antioxidants 2022, 11(5), 885; https://doi.org/10.3390/antiox11050885 - 29 Apr 2022

Cited by 11 | Viewed by 2724

Abstract

Thiyl radicals are exceptionally interesting reactive sulfur species (RSS), but rather rarely considered in a biological or medical context. We here review the reactivity of protein thiyl radicals in aqueous and lipid phases and provide an overview of their most relevant reaction partners in biological systems. We deduce that polyunsaturated fatty acids (PUFAs) are their preferred reaction substrates in lipid phases, whereas protein side chains arguably prevail in aqueous phases. In both cellular compartments, a single, dominating thiyl radical-specific antioxidant does not seem to exist. This conclusion is rationalized by the high reaction rate constants of thiyl radicals with several highly concentrated substrates in the cell, precluding effective interception by antioxidants, especially in lipid bilayers. The intractable reactivity of thiyl radicals may account for a series of long-standing, but still startling biochemical observations surrounding the amino acid cysteine: (i) its global underrepresentation on protein surfaces, (ii) its selective avoidance in aerobic lipid bilayers, especially the inner mitochondrial membrane, (iii) the inverse correlation between cysteine usage and longevity in animals, (iv) the mitochondrial synthesis and translational incorporation of cysteine persulfide, and potentially (v) the ex post introduction of selenocysteine into the genetic code. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Figure 1

16 pages, 9295 KiB

Open AccessReview

Heparan Sulfate, Mucopolysaccharidosis IIIB and Sulfur Metabolism Disorders

by Marta Kaczor-Kamińska, Kamil Kamiński and Maria Wróbel

Antioxidants 2022, 11(4), 678; https://doi.org/10.3390/antiox11040678 - 30 Mar 2022

Cited by 7 | Viewed by 2455

Abstract

Mucopolysaccharidosis, type IIIB (MPS IIIB) is a rare disease caused by mutations in the N-alpha-acetylglucosaminidase (NAGLU) gene resulting in decreased or absent enzyme activity. On the cellular level, the disorder is characterized by the massive lysosomal storage of heparan sulfate (HS)—one species of glycosaminoglycans. HS is a sulfur-rich macromolecule, and its accumulation should affect the turnover of total sulfur in cells; according to the studies presented here, it, indeed, does. The lysosomal degradation of HS in cells produces monosaccharides and inorganic sulfate (SO₄²⁻). Sulfate is a product of L-cysteine metabolism, and any disruption of its levels affects the entire L-cysteine catabolism pathway, which was first reported in 2019. It is known that L-cysteine level is elevated in cells with the Naglu^−/− gene mutation and in selected tissues of individuals with MPS IIIB. The level of glutathione and the Naglu^−/− cells’ antioxidant potential are significantly reduced, as well as the activity of 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) and the level of sulfane sulfur-containing compounds. The direct reason is not yet known. This paper attempts to identify some of cause-and-effect correlations that may lead to this condition and identifies research directions that should be explored. Full article

(This article belongs to the Special Issue Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy)

► Show Figures

Journal Menu

Journal Browser

Reactive Sulfur Species (RSS) in Physiological and Pathological Conditions and in Therapy

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (10 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI