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Antioxidants
Special Issues
Delivery of Gaseous Signal Molecules
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Delivery of Gaseous Signal Molecules

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 2021) | Viewed by 32214

Special Issue Editor

Dr. Urara Hasegawa

E-Mail Website
Guest Editor
Department of Materials Science and Engineering, Pennsylvania State University, State College, PA, USA
Interests: polymeric micelles; gaseous signal molecules; drug delivery system; stimuli-responsive biomaterials

Special Issue Information

Dear Colleagues,

Gaseous signal molecules such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S) and other gaseous molecules are produced in almost all tissues in the body and exert regulatory functions in various physiological and pathological processes. Despite the biological significance of these gases, the mechanisms of their biological actions are largely unknown and their therapeutic potential has not been well explored. This is partially due to the lack of gas delivery technologies, which mimics the endogenous production of these gaseous signal molecules in the body. These gases share several challenging characteristics such as high volatility, rapid diffusion, short half-lives under physiological conditions as well as complex dose-dependent biological activities. Therefore, there is a need to develop gas delivery systems that enable to deliver controlled amount of gaseous signal molecules for a specific period of time to target cells and tissues. 

This Special Issue welcomes original research papers and reviews focusing on gas delivery technologies, such as small gas donor compounds, biomaterials and medical devices, to expand our understanding of biological roles of gaseous signal molecules as well as to explore their therapeutic potential, which will lead to innovative approaches for the prevention and treatment of a wide variety of diseases.

Dr. Urara Hasegawa
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. 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

  • Nitric oxide
  • Carbon monoxide
  • Hydrogen sulfide
  • Gas donor compounds
  • Nanoparticles
  • Biomaterials
  • Medical devices

Published Papers (7 papers)

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Research

Jump to: Review

16 pages, 23041 KiB  
Article
Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma
by Charles E. Amankwa, Sudershan R. Gondi, Adnan Dibas, Courtney Weston, Arlene Funk, Tam Nguyen, Kytai T. Nguyen, Dorette Z. Ellis and Suchismita Acharya
Antioxidants 2021, 10(4), 575; https://doi.org/10.3390/antiox10040575 - 08 Apr 2021
Cited by 16 | Viewed by 3148
Abstract
Oxidative stress induced death and dysregulation of trabecular meshwork (TM) cells contribute to the increased intraocular pressure (IOP) in primary open angle (POAG) glaucoma patients. POAG is one of the major causes of irreversible vision loss worldwide. Nitric oxide (NO), a small gas [...] Read more.
Oxidative stress induced death and dysregulation of trabecular meshwork (TM) cells contribute to the increased intraocular pressure (IOP) in primary open angle (POAG) glaucoma patients. POAG is one of the major causes of irreversible vision loss worldwide. Nitric oxide (NO), a small gas molecule, has demonstrated IOP lowering activity in glaucoma by increasing aqueous humor outflow and relaxing TM. Glaucomatous pathology is associated with decreased antioxidant enzyme levels in ocular tissues causing increased reactive oxygen species (ROS) production that reduce the bioavailability of NO. Here, we designed, synthesized, and conducted in vitro studies of novel second-generation sulfur containing hybrid NO donor-antioxidants SA-9 and its active metabolite SA-10 to scavenge broad-spectrum ROS as well as provide efficient protection from t-butyl hydrogen peroxide (TBHP) induced oxidative stress while maintaining NO bioavailability in TM cells. To allow a better drug delivery, a slow release nanosuspension SA-9 nanoparticles (SA-9 NPs) was prepared, characterized, and tested in dexamethasone induced ocular hypertensive (OHT) mice model for IOP lowering activity. A single topical eye drop of SA-9 NPs significantly lowered IOP (61%) at 3 h post-dose, with the effect lasting up to 72 h. This class of molecule has high potential to be useful for treatment of glaucoma. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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15 pages, 1897 KiB  
Article
Generation of Rat Monoclonal Antibody to Detect Hydrogen Sulfide and Polysulfides in Biological Samples
by Shingo Kasamatsu, Yuki Kakihana, Taisei Koga, Hisashi Yoshioka and Hideshi Ihara
Antioxidants 2020, 9(11), 1160; https://doi.org/10.3390/antiox9111160 - 21 Nov 2020
Cited by 9 | Viewed by 2805
Abstract
Hydrogen sulfide (H2S) is endogenously produced by enzymes and via reactive persulfide/polysulfide degradation; it participates in a variety of biological processes under physiological and pathological conditions. H2S levels in biological fluids, such as plasma and serum, are correlated with [...] Read more.
Hydrogen sulfide (H2S) is endogenously produced by enzymes and via reactive persulfide/polysulfide degradation; it participates in a variety of biological processes under physiological and pathological conditions. H2S levels in biological fluids, such as plasma and serum, are correlated with the severity of various diseases. Therefore, development of a simple and selective H2S measurement method would be advantageous. This study aimed to generate antibodies specifically recognizing H2S derivatives and develop a colorimetric immunoassay for measuring H2S in biological samples. We used N-ethylmaleimide (NEM) as an H2S detection agent that forms a stable bis-S-adduct (NEM-S-NEM). We also prepared bis-S-heteroadduct with 3-maleimidopropionic acid, which, in conjugation with bovine serum albumin, was to immunize Japanese white rabbits and Wistar rats to enable generation of polyclonal and monoclonal antibodies, respectively. The generated antibodies were evaluated by competitive enzyme-linked immunosorbent assay. We could obtain two stable hybridoma cell lines producing monoclonal antibodies specific for NEM-S-NEM. By immunoassay with the monoclonal antibody, the H2S level in mouse plasma was determined as 0.2 μM, which was identical to the level detected by mass spectrometry. Taken together, these monoclonal antibodies can be a useful tool for a simple and highly selective immunoassay to detect H2S in biological samples. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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18 pages, 3521 KiB  
Article
Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BKCa Channels
by Yan Li, Jin Bai, Yi-hua Yang, Naoto Hoshi and Dong-bao Chen
Antioxidants 2020, 9(11), 1127; https://doi.org/10.3390/antiox9111127 - 13 Nov 2020
Cited by 16 | Viewed by 2253
Abstract
Opening of large conductance calcium-activated and voltage-dependent potassium (BKCa) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H2S) has been recently identified [...] Read more.
Opening of large conductance calcium-activated and voltage-dependent potassium (BKCa) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H2S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H2S-induced UA dilation is unknown. Here, we tested whether H2S activated BKCa channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BKCa subunits were found in human UA in vitro and hUASMC in vitro, and high β1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BKCa blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BKCa activity in hUASMC. H2S dose (NaHS, 1–1000 µM)-dependently potentiated BKCa currents and open probability. Co-incubation with a Ca2+ blocker nifedipine (5 µM) or a chelator (ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 5 mM) did not alter H2S-potentiated BKCa currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H2S stimulated human UA relaxation at least partially via activating SM BKCa channels independent of extracellular Ca2+. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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20 pages, 3168 KiB  
Article
The Inhibitory Effects of Slow-Releasing Hydrogen Sulfide Donors in the Mechanical Allodynia, Grip Strength Deficits, and Depressive-Like Behaviors Associated with Chronic Osteoarthritis Pain
by Gerard Batallé, Laura Cabarga and Olga Pol
Antioxidants 2020, 9(1), 31; https://doi.org/10.3390/antiox9010031 - 29 Dec 2019
Cited by 28 | Viewed by 3665
Abstract
Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl [...] Read more.
Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K/p-Akt, and maintained high levels of antioxidant/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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Review

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17 pages, 1465 KiB  
Review
Disrupted H2S Signaling by Cigarette Smoking and Alcohol Drinking: Evidence from Cellular, Animal, and Clinical Studies
by Ethan Read, Jiechun Zhu and Guangdong Yang
Antioxidants 2021, 10(1), 49; https://doi.org/10.3390/antiox10010049 - 03 Jan 2021
Cited by 11 | Viewed by 3388
Abstract
The role of endogenous hydrogen sulfide (H2S) as an antioxidant regulator has sparked interest in its function within inflammatory diseases. Cigarette and alcohol use are major causes of premature death, resulting from chronic oxidative stress and subsequent tissue damage. The activation [...] Read more.
The role of endogenous hydrogen sulfide (H2S) as an antioxidant regulator has sparked interest in its function within inflammatory diseases. Cigarette and alcohol use are major causes of premature death, resulting from chronic oxidative stress and subsequent tissue damage. The activation of the Nrf2 antioxidant response by H2S suggests that this novel gasotransmitter may function to prevent or potentially reverse disease progression caused by cigarette smoking or alcohol use. The purpose of this study is to review the interrelationship between H2S signaling and cigarette smoking or alcohol drinking. Based on the databases of cellular, animal, and clinical studies from Pubmed using the keywords of H2S, smoking, and/or alcohol, this review article provides a comprehensive insight into disrupted H2S signaling by alcohol drinking and cigarette smoking-caused disorders. Major signaling and metabolic pathways involved in H2S-derived antioxidant and anti-inflammatory responses are further reviewed. H2S supplementation may prove to be an invaluable asset in treating or preventing diseases in those suffering from cigarette or alcohol addiction. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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14 pages, 1452 KiB  
Review
Nitric Oxide Nano-Delivery Systems for Cancer Therapeutics: Advances and Challenges
by Long Binh Vong and Yukio Nagasaki
Antioxidants 2020, 9(9), 791; https://doi.org/10.3390/antiox9090791 - 26 Aug 2020
Cited by 29 | Viewed by 5904
Abstract
Nitric oxide (NO) plays important roles in various physiological and pathological functions and processes in the human body. Therapeutic application of NO molecules has been investigated in various diseases, including cardiovascular disease, cancer, and infections. However, the extremely short half-life of NO, which [...] Read more.
Nitric oxide (NO) plays important roles in various physiological and pathological functions and processes in the human body. Therapeutic application of NO molecules has been investigated in various diseases, including cardiovascular disease, cancer, and infections. However, the extremely short half-life of NO, which limits its clinical use considerably, along with non-specific distribution, has resulted in a low therapeutic index and undesired adverse effects. To overcome the drawbacks of using this gaseous signaling molecule, researchers in the last several decades have focused on innovative medical technologies, specifically nanoparticle-based drug delivery systems (DDSs), because these systems alter the biodistribution of the therapeutic agent through controlled release at the target tissues, resulting in a significant therapeutic drug effect. Thus, the application of nano-systems for NO delivery in the field of biomedicine, particularly in the development of new drugs for cancer treatment, has been increasing worldwide. In this review, we discuss NO delivery nanoparticle systems, with the aim of improving drug delivery development for conventional chemotherapies and controlling multidrug resistance in cancer treatments. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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31 pages, 5644 KiB  
Review
Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review
by Fan Rong, Yizhang Tang, Tengjiao Wang, Tao Feng, Jiang Song, Peng Li and Wei Huang
Antioxidants 2019, 8(11), 556; https://doi.org/10.3390/antiox8110556 - 15 Nov 2019
Cited by 101 | Viewed by 9774
Abstract
Polymeric materials releasing nitric oxide have attracted significant attention for therapeutic use in recent years. As one of the gaseous signaling agents in eukaryotic cells, endogenously generated nitric oxide (NO) is also capable of regulating the behavior of bacteria as well as biofilm [...] Read more.
Polymeric materials releasing nitric oxide have attracted significant attention for therapeutic use in recent years. As one of the gaseous signaling agents in eukaryotic cells, endogenously generated nitric oxide (NO) is also capable of regulating the behavior of bacteria as well as biofilm formation in many metabolic pathways. To overcome the drawbacks caused by the radical nature of NO, synthetic or natural polymers bearing NO releasing moiety have been prepared as nano-sized materials, coatings, and hydrogels. To successfully design these materials, the amount of NO released within a certain duration, the targeted pathogens and the trigger mechanisms upon external stimulation with light, temperature, and chemicals should be taken into consideration. Meanwhile, NO donors like S-nitrosothiols (RSNOs) and N-diazeniumdiolates (NONOates) have been widely utilized for developing antimicrobial polymeric agents through polymer-NO donor conjugation or physical encapsulation. In addition, antimicrobial materials with visible light responsive NO donor are also reported as strong and physiological friendly tools for rapid bacterial clearance. This review highlights approaches to delivery NO from different types of polymeric materials for combating diseases caused by pathogenic bacteria, which hopefully can inspire researchers facing common challenges in the coming ‘post-antibiotic’ era. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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