Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 74
Filter
1.
Antioxid Redox Signal ; 35(14): 1269-1270, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1510863

ABSTRACT

Cumpstey et al. (Antioxid Redox Signal 2021;10.1089/ars.2021.0017) have thoroughly reviewed the changes to the redox biology that determine individual resilience against COVID-19, and that hint at future treatment regimes. Verd and Verd question whether paracetamol, in the words of Cumpstey et al., "has the potential to overwhelm the body's ability to cope and maintain homeostasis" in COVID-19 patients. In response to this letter, the authors of Cumpstey et al. (Feelisch, Cumpstey, Clarka, Santolinic, and Jacksondargue) argue that what matters for human resilience against SARS-CoV-2 and other stressors is not simply determined by what is ingested/inhaled but also by how these substances can be handled by the body. The ability to cope with competing demands is determined by the extent to which the building blocks essential for cell/organ protection, function, adjustment, and healing can continue to be made available in sufficient quantities. To this end, dietary quality and nutrient status are fundamental determinants of the metabolic background against which all of these factors (including over-the-counter medications such as paracetamol) operate and either support or compromise the balanced functioning of the reactive species interactome.


Subject(s)
COVID-19 , Pandemics , Diet , Humans , Oxidation-Reduction , SARS-CoV-2
2.
Mech Ageing Dev ; 199: 111551, 2021 10.
Article in English | MEDLINE | ID: covidwho-1492370

ABSTRACT

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox®), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Drug Development , NF-E2-Related Factor 2/metabolism , Organoids/drug effects , Oxidative Stress/drug effects , Polyphenols/pharmacology , Vitamin D/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacology , COVID-19/drug therapy , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Humans , NF-E2-Related Factor 2/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Organoids/metabolism , Oxidation-Reduction , Oxidative Stress/genetics
3.
Environ Sci Technol ; 55(17): 12009-12018, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1483072

ABSTRACT

Diatrizoate, a refractory ionic iodinated X-ray contrast media (ICM) compound, cannot be efficiently degraded in a complex wastewater matrix even by advanced oxidation processes. We report in this research that a homogeneous process, thiourea dioxide (TDO) coupled with trace Cu(II) (several micromoles, ubiquitous in some wastewater), is effective for reductive deiodination and degradation of diatrizoate at neutral pH values. Specifically, the molar ratio of iodide released to TDO consumed reached 2 under ideal experimental conditions. TDO eventually decomposed into urea and sulfite/sulfate. Based on the results of diatrizoate degradation, TDO decomposition, and Cu(I) generation and consumption during the TDO-Cu(II) reaction, we confirmed that Cu(I) is responsible for diatrizoate degradation. However, free Cu(I) alone did not work. It was proposed that Cu(I) complexes are actual reactive species toward diatrizoate. Inorganic anions and effluent organic matter negatively influence diatrizoate degradation, but by increasing the TDO dosage, as well as extending the reaction time, its degradation efficiency can still be guaranteed for real hospital wastewater. This reduction reaction could be potentially useful for in situ deiodination and degradation of diatrizoate in hospital wastewater before discharge into municipal sewage networks.


Subject(s)
Diatrizoate , Water Pollutants, Chemical , Contrast Media , Oxidation-Reduction , Thiourea/analogs & derivatives , Waste Water , Water Pollutants, Chemical/analysis
5.
Antioxid Redox Signal ; 35(14): 1207-1225, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1475726

ABSTRACT

Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.


Subject(s)
Acetylcysteine/metabolism , COVID-19/metabolism , Hydrogen Sulfide/metabolism , Humans , Oxidation-Reduction
6.
Front Immunol ; 12: 699389, 2021.
Article in English | MEDLINE | ID: covidwho-1450805

ABSTRACT

The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of "nutritional immunity" to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to >8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to >150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations' Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893-0.6849, p-value < 0.0003] as well as incidence [r (23):0.8084-0.5658; p-value < 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients' data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.


Subject(s)
COVID-19/diet therapy , COVID-19/mortality , SARS-CoV-2/drug effects , Zinc/blood , Zinc/therapeutic use , COVID-19/epidemiology , Comorbidity , Dietary Supplements , Europe/epidemiology , Humans , Oxidation-Reduction/drug effects , Oxidative Stress , SARS-CoV-2/immunology
7.
J Am Chem Soc ; 143(40): 16777-16785, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1442692

ABSTRACT

The most recent global health crisis caused by the SARS-CoV-2 outbreak and the alarming use of chemical warfare agents highlight the necessity to produce efficient protective clothing and masks against biohazard and chemical threats. However, the development of a multifunctional protective textile is still behind to supply adequate protection for the public. To tackle this challenge, we designed multifunctional and regenerable N-chlorine based biocidal and detoxifying textiles using a robust zirconium metal-organic framework (MOF), UiO-66-NH2, as a chlorine carrier which can be easily coated on textile fibers. A chlorine bleaching converted the amine groups located on the MOF linker to active N-chlorine structures. The fibrous composite exhibited rapid biocidal activity against both Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) with up to a 7 log reduction within 5 min for each strain as well as a 5 log reduction of SARS-CoV-2 within 15 min. Moreover, the active chlorine loaded MOF/fiber composite selectively and rapidly degraded sulfur mustard and its chemical simulant 2-chloroethyl ethyl sulfide (CEES) with half-lives less than 3 minutes. The versatile MOF-based fibrous composite designed here has the potential to serve as protective cloth against both biological and chemical threats.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Chemical Warfare Agents/chemistry , Chlorine/pharmacology , Metal-Organic Frameworks/pharmacology , Protective Clothing , Animals , Anti-Bacterial Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Cell Line , Chlorine/chemistry , Escherichia coli/drug effects , Halogenation , Humans , Metal-Organic Frameworks/chemical synthesis , Microbial Sensitivity Tests , Mustard Gas/analogs & derivatives , Mustard Gas/chemistry , Oxidation-Reduction , SARS-CoV-2/drug effects , Staphylococcus aureus/drug effects , Textiles , Zirconium/chemistry
8.
Oxid Med Cell Longev ; 2021: 9221693, 2021.
Article in English | MEDLINE | ID: covidwho-1438138

ABSTRACT

Objective: Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated. Methods: The total content (t) and reduced forms (r) of aminothiols were determined in patients with COVID-19 (n = 59) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification. Results: Low tGSH level was associated with the risk of severe COVID-19 (tGSH ≤ 1.5 µM, mild vs. moderate/severe: risk ratio (RR) = 3.09, p = 0.007) and degree of lung damage (tGSH ≤ 1.8 µM, CT < 2 vs. CT ≥ 2: RR = 2.14, p = 0.0094). The rGSH level showed a negative association with D-dimer levels (ρ = -0.599, p = 0.014). Low rCG level was also associated with the risk of lung damage (rCG ≤ 1.3 µM, CT < 2 vs. CT ≥ 2: RR = 2.28, p = 0.001). Levels of rCG (ρ = -0.339, p = 0.012) and especially tCG (ρ = -0.551, p = 0.004) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19. Conclusion: Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19.


Subject(s)
COVID-19/diagnosis , Dipeptides/blood , Glutathione/blood , Advanced Oxidation Protein Products/blood , Aged , Amino Acids, Sulfur/blood , Biomarkers/blood , COVID-19/blood , COVID-19/pathology , Dipeptides/metabolism , Female , Glutathione/metabolism , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Oxidation-Reduction , SARS-CoV-2/isolation & purification , Severity of Illness Index
9.
Mikrochim Acta ; 188(10): 335, 2021 Sep 09.
Article in English | MEDLINE | ID: covidwho-1411927

ABSTRACT

A practical colorimetric assay was developed for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, magnetic γ Fe2O3 nanoparticles were synthesized and used as a peroxidase-like mimic activity molecule. In the presence of γ Fe2O3 nanoparticles, the color change of H2O2 included 3,3',5,5'-tetramethylbenzidine was monitored at the wavelength of 654 nm when spike protein interacted with angiotensin-converting enzyme 2 receptor. This oxidation-reduction reaction was examined both spectroscopically and by using electrochemical techniques. The experimental parameters were optimized and the analytical characteristics investigated. The developed assay was applied to real SARS-CoV-2 samples, and very good results that were in accordance with the real time polymerase chain reaction were obtained.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Colorimetry/methods , Magnetic Iron Oxide Nanoparticles/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Benzidines/chemistry , Biosensing Techniques/methods , COVID-19 Testing/instrumentation , Catalysis , Chromogenic Compounds/chemistry , Cysteine/chemistry , Humans , Hydrogen Peroxide/chemistry , Limit of Detection , Nasopharynx/virology , Oropharynx/virology , Oxidation-Reduction , Peroxidase/chemistry , Spike Glycoprotein, Coronavirus/metabolism
10.
Eur Rev Med Pharmacol Sci ; 25(16): 5304-5309, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1395677

ABSTRACT

OBJECTIVE: There is more pronounced hypercoagulation in COVID-19 infection than in other viral lung infections. Oxidized phospholipids (OxPLs) appear in COVID-19-infected lungs due to oxidative stress, after which they promote the induction of tissue factor (TF) expression and inflammatory programmers in monocytes, as well as activate endothelial cells to recruit and bind to monocytes. Therefore, we aimed to demonstrate the role of OxPLs in inflammatory and procoagulant responses in COVID-19 infection. PATIENTS AND METHODS: Patients with a positive SARS-CoV-2 polymerase chain reaction test and ten healthy donors were included in the study. Peripheral blood was drawn at inclusion for OxPAPC, IFN-γ, and CCL2 serum level measurements. Clinical data were collected from electronic patient medical files. The serum levels of OxPAPC, IFNγ, and CCL2 were measured by immune assays. RESULTS: Seventy-two patients were included in the study. OxPAPC and CCL2 were higher in the patients than in the controls (<0.003 and 0.011, respectively). INF-γ did not significantly differ between groups. There was no difference between the patients with lung involvement and those without CCL2, INF-γ, and OxPAPC. D-dimer, CRP, and ferritin were higher in the patients with lung involvement. Serum levels of INF-γ and CCL2 were positively correlated with each other (r:0.757, p<0.0001), but no correlation was detected between OxPAPC and INF-γ or CCL2. There was no correlation between OxPAPC and hematologic or biochemical parameters. CONCLUSIONS: OxPAPC, which is thought to contribute to hypercoagulability, was found to be high in the patients with Covid-19 infection. The role of OxPLs in COVID-19-associated hypercoagulopathy should be investigated further in experimental models and in larger patient groups.


Subject(s)
Blood Coagulation , COVID-19/blood , Phospholipids/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Oxidative Stress , SARS-CoV-2/isolation & purification , Young Adult
11.
Molecules ; 26(17)2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1390702

ABSTRACT

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase "super substrates" that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.


Subject(s)
Immunity, Innate , Leukocyte Elastase/metabolism , Methionine/analogs & derivatives , Neutrophils/immunology , Biocatalysis , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Catalytic Domain/genetics , Enzyme Assays , Host-Pathogen Interactions/immunology , Humans , Leukocyte Elastase/antagonists & inhibitors , Leukocyte Elastase/genetics , Lung/immunology , Lung/pathology , Lung/virology , Methionine/metabolism , Molecular Dynamics Simulation , Neutrophil Infiltration , Neutrophils/enzymology , Oxidation-Reduction/drug effects , Proteolysis/drug effects , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/pathology , SARS-CoV-2/immunology , Substrate Specificity/immunology
12.
Int J Mol Sci ; 22(9)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1389396

ABSTRACT

Chloroxylenol (PCMX) is applied as a preservative and disinfectant in personal care products, currently recommended for use to inactivate the SARS-CoV-2 virus. Its intensive application leads to the release of PCMX into the environment, which can have a harmful impact on aquatic and soil biotas. The aim of this study was to assess the mechanism of chloroxylenol biodegradation by the fungal strains Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373, and investigate the ecotoxicity of emerging by-products. The residues of PCMX and formed metabolites were analysed using GC-MS. The elimination of PCMX in the cultures of tested microorganisms was above 70%. Five fungal by-products were detected for the first time. Identified intermediates were performed by dechlorination, hydroxylation, and oxidation reactions catalysed by cytochrome P450 enzymes and laccase. A real-time quantitative PCR analysis confirmed an increase in CYP450 genes expression in C. elegans cells. In the case of T. versicolor, spectrophotometric measurement of the oxidation of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) showed a significant rise in laccase activity during PCMX elimination. Furthermore, with the use of bioindicators from different ecosystems (Daphtoxkit F and Phytotoxkit), it was revealed that the biodegradation process of PCMX had a detoxifying nature.


Subject(s)
Cunninghamella/metabolism , Trametes/metabolism , Xylenes/metabolism , Animals , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Daphnia/drug effects , Daphnia/physiology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation , Laccase/metabolism , Oxidation-Reduction , Toxicity Tests , Xylenes/analysis , Xylenes/pharmacology
13.
Molecules ; 26(16)2021 Aug 19.
Article in English | MEDLINE | ID: covidwho-1376915

ABSTRACT

G-quadruplexes (G4s) are higher-order supramolecular structures, biologically important in the regulation of many key processes. Among all, the recent discoveries relating to RNA-G4s, including their potential involvement as antiviral targets against COVID-19, have triggered the ever-increasing need to develop selective molecules able to interact with parallel G4s. Naphthalene diimides (NDIs) are widely exploited as G4 ligands, being able to induce and strongly stabilize these structures. Sometimes, a reversible NDI-G4 interaction is also associated with an irreversible one, due to the cleavage and/or modification of G4s by functional-NDIs. This is the case of NDI-Cu-DETA, a copper(II) complex able to cleave G4s in the closest proximity to the target binding site. Herein, we present two original Cu(II)-NDI complexes, inspired by NDI-Cu-DETA, differently functionalized with 2-(2-aminoethoxy)ethanol side-chains, to selectively drive redox-catalyzed activity towards parallel G4s. The selective interaction toward parallel G4 topology, controlled by the presence of 2-(2-aminoethoxy)ethanol side chains, was already firmly demonstrated by us using core-extended NDIs. In the present study, the presence of protonable moieties and the copper(II) cavity, increases the binding affinity and specificity of these two NDIs for a telomeric RNA-G4. Once defined the copper coordination relationship and binding constants by competition titrations, ability in G4 stabilization, and ROS-induced cleavage were analyzed. The propensity in the stabilization of parallel topology was highlighted for both of the new compounds HP2Cu and PE2Cu. The results obtained are particularly promising, paving the way for the development of new selective functional ligands for binding and destructuring parallel G4s.


Subject(s)
Coordination Complexes/chemistry , Copper/chemistry , G-Quadruplexes , Imides/chemistry , Naphthalenes/chemistry , Binding Sites , DEET/chemistry , Ligands , Oxidation-Reduction , Polyethylene Glycols/chemistry , Structure-Activity Relationship
14.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Article in English | MEDLINE | ID: covidwho-1360221

ABSTRACT

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called "long COVID-19," reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.


Subject(s)
COVID-19/metabolism , Encephalomyelitis/metabolism , Fatigue Syndrome, Chronic/metabolism , Animals , COVID-19/complications , COVID-19/etiology , COVID-19/immunology , Encephalomyelitis/immunology , Fatigue Syndrome, Chronic/immunology , Humans , Oxidation-Reduction
15.
Biomed Chromatogr ; 35(12): e5212, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1349236

ABSTRACT

Remdesivir (RDV) is the first antiviral drug, approved by the Food and Drug Administration, to treat severe acute respiratory syndrome coronavirus 2. RDV is a relatively new chemical entity, 'ester prodrug', with no reported stability profile. Due to the urgency of its use and thus fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried out on a C18 column (250 × 4.6 mm, 5 µm) with dual detection: diode array at 240 nm and fluorescence at λex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in the ratio of 55:45 (v/v), respectively, was used. The linearity range using HPLC-diode array detection was 0.1-15 µg/mL, whereas that using fluorimetric detection was 0.05-15 µg/mL. As per the International Conference on Harmonization guidelines, RDV has been degraded by accelerated alkaline, acidic, neutral hydrolysis, oxidative, heat, and photolytic stress conditions. Possible degradation hypothesis of the parent molecule has been suggested and illustrated. The proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. The developed methods were fully validated and proved suitable for quality control routine analysis of RDV in raw material and pharmaceutical dosage forms.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/chemistry , COVID-19/drug therapy , Prodrugs/chemistry , Acetonitriles/chemistry , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/pharmacology , Alanine/chemistry , Alanine/pharmacology , Antiviral Agents/pharmacology , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Drug Stability , Hot Temperature , Humans , Hydrolysis , Limit of Detection , Oxidation-Reduction , Photolysis
16.
Reprod Fertil Dev ; 33(12): 683-690, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1331436

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing coronavirus disease 2019 (COVID-19). Because COVID-19 is a multisystem infection, there are some concerns regarding its possible effects on male fertility. This study aimed to investigate the effects of COVID-19 on semen oxidative status and parameters 14 and 120 days after diagnosis in patients presenting with moderate infection (defined as respiratory symptoms, with or without fever, with Spo2 <93% and >90% and lung involvement <50%). Semen samples were obtained from 20 participants at two time points: the first sample on Day 14 and the second on Day 120 after diagnosis. Semen parameters (sperm concentration, motility, morphology, and viability) were evaluated, as were levels of seminal reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC) and sperm DNA fragmentation. Semen parameters, including sperm motility and DNA integrity, improved at 120 days after the COVID-19 diagnosis relative to values at 14 days. In addition, ROS and MDA levels were significantly reduced in patients 120 days after infection, and TAC increased at 120 days compared with 14 days (during the acute stage of infection). In conclusion, the present study shows that the detrimental effects of COVID-19 on sperm properties caused by oxidative stress decrease up to Day 120 after diagnosis.


Subject(s)
COVID-19/metabolism , Oxidative Stress , Semen/metabolism , Spermatozoa/metabolism , Adult , COVID-19/diagnosis , DNA Fragmentation , Humans , Male , Malondialdehyde/metabolism , Middle Aged , Oxidation-Reduction , Prospective Studies , Reactive Oxygen Species/metabolism , Semen Analysis , Severity of Illness Index , Sperm Count , Sperm Motility , Spermatozoa/pathology , Time Factors , Young Adult
17.
Antioxid Redox Signal ; 35(14): 1269-1270, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1322602

ABSTRACT

Cumpstey et al. (Antioxid Redox Signal 2021;10.1089/ars.2021.0017) have thoroughly reviewed the changes to the redox biology that determine individual resilience against COVID-19, and that hint at future treatment regimes. Verd and Verd question whether paracetamol, in the words of Cumpstey et al., "has the potential to overwhelm the body's ability to cope and maintain homeostasis" in COVID-19 patients. In response to this letter, the authors of Cumpstey et al. (Feelisch, Cumpstey, Clarka, Santolinic, and Jacksondargue) argue that what matters for human resilience against SARS-CoV-2 and other stressors is not simply determined by what is ingested/inhaled but also by how these substances can be handled by the body. The ability to cope with competing demands is determined by the extent to which the building blocks essential for cell/organ protection, function, adjustment, and healing can continue to be made available in sufficient quantities. To this end, dietary quality and nutrient status are fundamental determinants of the metabolic background against which all of these factors (including over-the-counter medications such as paracetamol) operate and either support or compromise the balanced functioning of the reactive species interactome.


Subject(s)
COVID-19 , Pandemics , Diet , Humans , Oxidation-Reduction , SARS-CoV-2
18.
J Am Chem Soc ; 143(30): 11544-11553, 2021 08 04.
Article in English | MEDLINE | ID: covidwho-1319014

ABSTRACT

Exponential molecular amplification such as the polymerase chain reaction is a powerful tool that allows ultrasensitive biodetection. Here, we report a new exponential amplification strategy based on photoredox autocatalysis, where eosin Y, a photocatalyst, amplifies itself by activating a nonfluorescent eosin Y derivative (EYH3-) under green light. The deactivated photocatalyst is stable and rapidly activated under low-intensity light, making the eosin Y amplification suitable for resource-limited settings. Through steady-state kinetic studies and reaction modeling, we found that EYH3- is either oxidized to eosin Y via one-electron oxidation by triplet eosin Y and subsequent 1e-/H+ transfer, or activated by singlet oxygen with the risk of degradation. By reducing the rate of the EYH3- degradation, we successfully improved EYH3--to-eosin Y recovery, achieving efficient autocatalytic eosin Y amplification. Additionally, to demonstrate its flexibility in output signals, we coupled the eosin Y amplification with photoinduced chromogenic polymerization, enabling sensitive visual detection of analytes. Finally, we applied the exponential amplification methods in developing bioassays for detection of biomarkers including SARS-CoV-2 nucleocapsid protein, an antigen used in the diagnosis of COVID-19.


Subject(s)
Coronavirus Nucleocapsid Proteins/analysis , Eosine Yellowish-(YS)/analogs & derivatives , Spectrometry, Fluorescence/methods , 3,3'-Diaminobenzidine/chemistry , Biomarkers/chemistry , Catalysis/radiation effects , Eosine Yellowish-(YS)/chemical synthesis , Eosine Yellowish-(YS)/radiation effects , Fluorescence , Light , Limit of Detection , Oxidation-Reduction/radiation effects , Phosphoproteins/analysis , Polyethylene Glycols/chemistry , Polymerization , Proof of Concept Study , SARS-CoV-2/chemistry
19.
Adv Sci (Weinh) ; 8(18): e2101498, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316192

ABSTRACT

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.


Subject(s)
Acute Kidney Injury/drug therapy , Antioxidants/pharmacology , Oxidation-Reduction/drug effects , Polyvinyls/pharmacology , Pyrrolidines/pharmacology , Titanium/pharmacology , Acute Kidney Injury/metabolism , Apoptosis/drug effects , Humans , Kidney/drug effects , Kidney/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
20.
J Inorg Biochem ; 223: 111546, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1313251

ABSTRACT

Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled "cytokine storm". This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.


Subject(s)
Antioxidants/pharmacology , COVID-19/drug therapy , Melatonin/pharmacology , Reactive Oxygen Species/metabolism , Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , COVID-19/immunology , COVID-19/metabolism , Cytokine Release Syndrome/immunology , Cytokines/metabolism , Hemeproteins/metabolism , Humans , Hypochlorous Acid/metabolism , Nitric Oxide/metabolism , Oxidation-Reduction , Oxidative Stress/drug effects , Peroxidase/metabolism , SARS-CoV-2 , Sleep/drug effects , Vitamin B Deficiency/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...