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1.
Oxid Med Cell Longev ; 2022: 8067857, 2022.
Article in English | MEDLINE | ID: covidwho-2138250

ABSTRACT

Background: Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods: The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results: Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions: Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.


Subject(s)
COVID-19 , Humans , Prospective Studies , SARS-CoV-2 , Lipoproteins , Oxidation-Reduction , Antioxidants
2.
J Transl Med ; 20(1): 549, 2022 Nov 26.
Article in English | MEDLINE | ID: covidwho-2139331

ABSTRACT

BACKGROUND: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. METHODS: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. RESULTS: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. CONCLUSIONS: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.


Subject(s)
COVID-19 , Osteoarthritis , Animals , Mice , Humans , Endoplasmic Reticulum Stress , Pandemics , Oxidation-Reduction , Homeostasis , Osteoarthritis/drug therapy , Antiviral Agents
3.
Redox Biol ; 56: 102465, 2022 10.
Article in English | MEDLINE | ID: covidwho-2105815

ABSTRACT

BACKGROUND: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. METHODS: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. RESULTS: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. CONCLUSION: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.


Subject(s)
COVID-19 , Antioxidants/metabolism , Electron Spin Resonance Spectroscopy , Free Radicals , Humans , Hydrogen Peroxide , Intercellular Adhesion Molecule-1/metabolism , Interleukin-17/metabolism , Nitrates , Nitrites , Oxidants/metabolism , Oxidation-Reduction , Oxidative Stress , RNA, Messenger/metabolism , Uric Acid , Vascular Cell Adhesion Molecule-1/metabolism
4.
Chemistry ; 28(48): e202200906, 2022 Aug 26.
Article in English | MEDLINE | ID: covidwho-2047510

ABSTRACT

This paper describes a synthesis of ALC-0315 by a sequence that more than doubles the overall yield relative to the published one, and that employs much cleaner reactions, thereby facilitating purifications to a considerable extent.


Subject(s)
COVID-19 Vaccines , COVID-19 , Amination , Amino Alcohols , COVID-19/prevention & control , Decanoates , Humans , Lipids , Oxidation-Reduction , Vaccines, Synthetic , mRNA Vaccines
5.
PLoS One ; 17(9): e0274910, 2022.
Article in English | MEDLINE | ID: covidwho-2039433

ABSTRACT

It is well known that the presence of comorbidities and age-related health issues may hide biochemical and metabolic features triggered by SARS-CoV-2 infection and other diseases associated to hypoxia, as they are by themselves chronic inflammatory conditions that may potentially disturb metabolic homeostasis and thereby negatively impact on COVID-19 progression. To unveil the metabolic abnormalities inherent to hypoxemia caused by COVID-19, we here applied gas chromatography coupled to mass spectrometry to analyze the main metabolic changes exhibited by a population of male patients less than 50 years of age with mild/moderate and severe COVID-19 without pre-existing comorbidities known to predispose to life-threatening complications from this infection. Several differences in serum levels of particular metabolites between normal controls and patients with COVID-19 as well as between mild/moderate and severe COVID-19 were identified. These included increased glutamic acid and reduced glutamine, cystine, threonic acid, and proline levels. In particular, using the entire metabolomic fingerprint obtained, we observed that glutamine/glutamate metabolism was associated with disease severity as patients in the severe COVID-19 group presented the lowest and higher serum levels of these amino acids, respectively. These data highlight the hypoxia-derived metabolic alterations provoked by SARS-CoV-2 infection in the absence of pre-existing co-morbidities as well as the value of amino acid metabolism in determining reactive oxygen species recycling pathways, which when impaired may lead to increased oxidation of proteins and cell damage. They also provide insights on new supportive therapies for COVID-19 and other disorders that involve altered redox homeostasis and lower oxygen levels that may lead to better outcomes of disease severity.


Subject(s)
COVID-19 , Glutamic Acid , Amino Acids/metabolism , Cystine/metabolism , Gas Chromatography-Mass Spectrometry , Glutamic Acid/metabolism , Glutamine/metabolism , Homeostasis , Humans , Hypoxia , Male , Oxidation-Reduction , Oxygen , Proline/metabolism , Reactive Oxygen Species , SARS-CoV-2
6.
Sci Total Environ ; 850: 157851, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2036502

ABSTRACT

The rapid spread of coronavirus disease 2019 has increased the consumption of some antiviral drugs, wherein these are discharged into wastewater, posing risks to the ecosystem and human health. Therefore, efforts are being made for the development of advanced oxidation processes (AOPs) to remediate water containing these pharmaceuticals. Here, the toxicity evolution of the antiviral drug ribavirin (RBV) was systematically investigated during its degradation via the UV/TiO2/H2O2 advanced oxidation process. Under optimal conditions, RBV was almost completely eliminated within 20 min, although the mineralization rate was inadequate. Zebrafish embryo testing revealed that the ecotoxicity of the treated RBV solutions increased at some stages and decreased as the reaction time increased, which may be attributed to the formation and decomposition of various transformation products (TPs). Liquid chromatography-mass spectrometry analysis along with density functional theory calculations helped identify possible toxicity increase-causing TPs, and quantitative structure activity relationship prediction revealed that most TPs exhibit higher toxicity than the parent compound. The findings of this study suggest that, in addition to the removal rate of organics, the potential ecotoxicity of treated effluents should also be considered when AOPs are applied in wastewater treatment.


Subject(s)
COVID-19 , Water Pollutants, Chemical , Water Purification , Animals , Antiviral Agents/analysis , Antiviral Agents/toxicity , Ecosystem , Humans , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Pharmaceutical Preparations , Ribavirin/toxicity , Ultraviolet Rays , Waste Water/chemistry , Water/analysis , Water Pollutants, Chemical/analysis , Water Purification/methods , Zebrafish
7.
Huan Jing Ke Xue ; 43(9): 4597-4607, 2022 Sep 08.
Article in Chinese | MEDLINE | ID: covidwho-2025656

ABSTRACT

The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO4-·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of CQP and major free radicals to explore its mechanism of influence. The results showed that the degradation efficiency of CQP could reach 91.3% after 10 min under UV/PS, which was significantly higher than that under UV, sunlight, or PS alone. At pH=6.9, the second-order rate reaction constants of CQP with HO· and SO4-· were 8.9×109 L·(mol·s)-1and 1.4×1010 L·(mol·s)-1, respectively, and the main active species was SO4-·. The degradation rate of CQP increased with increasing concentrations of PS and decreased with the addition of HCO3- and Cl-. The removal efficiency of CQP was inhibited under stronger alkaline conditions. N-de-ethylation, cleavage of the C-N bond, and hydrogen abstraction were proposed as the principal pathways of CQP degradation based on LC-MS analysis. The mineralization rate of CQP could be improved by increasing PS concentration and pH values. This study could be helpful for the treatment of anti-COVID-19 pharmaceutical wastewater.


Subject(s)
Water Pollutants, Chemical , Chloroquine/analogs & derivatives , Hydroxyl Radical/analysis , Hydroxyl Radical/chemistry , Oxidation-Reduction , Waste Water/analysis , Water Pollutants, Chemical/analysis
8.
Int J Mol Sci ; 23(17)2022 Sep 03.
Article in English | MEDLINE | ID: covidwho-2010113

ABSTRACT

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.


Subject(s)
Advanced Oxidation Protein Products , COVID-19 , Advanced Oxidation Protein Products/metabolism , Albumins/metabolism , Humans , Oxidation-Reduction , Oxidative Stress
9.
Cell Biochem Funct ; 40(7): 694-705, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1990431

ABSTRACT

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death.


Subject(s)
COVID-19 , Antioxidants/metabolism , C-Reactive Protein/metabolism , Humans , Interleukin-6/metabolism , Oxidation-Reduction , Reactive Oxygen Species/metabolism , SARS-CoV-2
10.
Environ Sci Pollut Res Int ; 29(45): 67604-67640, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1982293

ABSTRACT

This review summarizes research data on the pharmaceutical drugs used to treat the novel SARS-CoV-2 virus, their characteristics, environmental impacts, and the advanced oxidation processes (AOP) applied to remove them. A literature survey was conducted using the electronic databases Science Direct, Scopus, Taylor & Francis, Google Scholar, PubMed, and Springer. This complete research includes and discusses relevant studies that involve the introduction, pharmaceutical drugs used in the SARS-CoV-2 pandemic: chemical characteristics and environmental impact, advanced oxidation process (AOP), future trends and discussion, and conclusions. The results show a full approach in the versatility of AOPs as a promising solution to minimize the environmental impact associated with these compounds by the fact that they offer different ways for hydroxyl radical production. Moreover, this article focuses on introducing the fundamentals of each AOP, the main parameters involved, and the concomitance with other sources and modifications over the years. Photocatalysis, sonochemical technologies, electro-oxidation, photolysis, Fenton reaction, ozone, and sulfate radical AOP have been used to mineralize SARS-CoV-2 pharmaceutical compounds, and the efficiencies are greater than 65%. According to the results, photocatalysis is the main technology currently applied to remove these pharmaceuticals. This process has garnered attention because solar energy can be directly utilized; however, low photocatalytic efficiencies and high costs in large-scale practical applications limit its use. Furthermore, pharmaceuticals in the environment are diverse and complex. Finally, the review also provides ideas for further research needs and major concerns.


Subject(s)
COVID-19 , Ozone , Water Pollutants, Chemical , Water Purification , Humans , Hydrogen Peroxide/chemistry , Hydroxyl Radical/chemistry , Oxidation-Reduction , Ozone/chemistry , Pharmaceutical Preparations , SARS-CoV-2 , Sunlight , Waste Water/chemistry , Water , Water Pollutants, Chemical/analysis , Water Purification/methods
12.
Nature ; 609(7928): 801-807, 2022 09.
Article in English | MEDLINE | ID: covidwho-1960390

ABSTRACT

Anorexia and fasting are host adaptations to acute infection, and induce a metabolic switch towards ketogenesis and the production of ketone bodies, including ß-hydroxybutyrate (BHB)1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we show that the production of BHB is impaired in individuals with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) but not in those with  influenza-induced ARDS. We found that BHB promotes both the survival of and the production of interferon-γ by CD4+ T cells. Applying a metabolic-tracing analysis, we established that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but could be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we show in mice that a ketogenic diet and the delivery of BHB as a ketone ester drink restores CD4+ T cell metabolism and function in severe respiratory infections, ultimately reducing the mortality of mice infected with SARS-CoV-2. Altogether, our data reveal that BHB is an alternative source of carbon that promotes T cell responses in pulmonary viral infections, and highlight impaired ketogenesis as a potential confounding factor in severe COVID-19.


Subject(s)
COVID-19 , Energy Metabolism , Ketones , Respiratory Distress Syndrome , SARS-CoV-2 , T-Lymphocytes , 3-Hydroxybutyric Acid/biosynthesis , 3-Hydroxybutyric Acid/metabolism , Amino Acids/biosynthesis , Amino Acids/metabolism , Animals , COVID-19/complications , COVID-19/immunology , COVID-19/pathology , Diet, Ketogenic , Esters/metabolism , Glutathione/biosynthesis , Glutathione/metabolism , Glycolysis , Interferon-gamma/biosynthesis , Ketone Bodies/metabolism , Ketones/metabolism , Mice , Orthomyxoviridae/pathogenicity , Oxidation-Reduction , Oxidative Phosphorylation , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology
13.
Methods Mol Biol ; 2511: 333-344, 2022.
Article in English | MEDLINE | ID: covidwho-1941387

ABSTRACT

Infection with SARS-CoV-2, the causative agent of COVID-19, causes numerous cellular dysfunctions. The virus enters the host cells and hijacks the cell machinery for its replication, resulting in disturbances of the oxidative, reductive balance, increased production of damaging reactive oxygen species (ROS), and mitochondrial dysfunction. This damaging cycle can make cells less resistant to infection and make the host more likely to experience a severe disease course. Treatment with antioxidants has been tested as a potential approach to reduce the effects of this disorder. Here, we present a protocol to assess the impact of treatment with a mixture of curcuminoids on physiological and molecular biomarkers, focusing on determining total antioxidant capacity. We used a cohort of diabetes patients with an imbalance in redox mechanisms as such patients are more likely to become severely ill from COVID-19 than healthy persons.


Subject(s)
COVID-19 , Antioxidants/metabolism , Antioxidants/therapeutic use , Humans , Oxidation-Reduction , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , SARS-CoV-2
14.
Int J Mol Sci ; 23(1)2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1938830

ABSTRACT

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term "oxidative stress" is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.


Subject(s)
Homeostasis/physiology , Animals , Circadian Rhythm/physiology , Humans , Oxidation-Reduction , Oxidative Stress/physiology , Precision Medicine , Signal Transduction/physiology
15.
Int J Mol Sci ; 23(11)2022 May 31.
Article in English | MEDLINE | ID: covidwho-1892899

ABSTRACT

We studied the kinetics of the reaction of N-acetyl-l-cysteine (NAC or RSH) with cupric ions at an equimolar ratio of the reactants in aqueous acid solution (pH 1.4-2) using UV/Vis absorption and circular dichroism (CD) spectroscopies. Cu2+ showed a strong catalytic effect on the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical (ABTSr) consumption and autoxidation of NAC. Difference spectra revealed the formation of intermediates with absorption maxima at 233 and 302 nm (ε302/Cu > 8 × 103 M-1 cm-1) and two positive Cotton effects centered at 284 and 302 nm. These intermediates accumulate during the first, O2-independent, phase of the NAC autoxidation. The autocatalytic production of another chiral intermediate, characterized by two positive Cotton effects at 280 and 333 nm and an intense negative one at 305 nm, was observed in the second reaction phase. The intermediates are rapidly oxidized by added ABTSr; otherwise, they are stable for hours in the reaction solution, undergoing a slow pH- and O2-dependent photosensitive decay. The kinetic and spectral data are consistent with proposed structures of the intermediates as disulfide-bridged dicopper(I) complexes of types cis-/trans-CuI2(RS)2(RSSR) and CuI2(RSSR)2. The electronic transitions observed in the UV/Vis and CD spectra are tentatively attributed to Cu(I) → disulfide charge transfer with an interaction of the transition dipole moments (exciton coupling). The catalytic activity of the intermediates as potential O2 activators via Cu(II) peroxo-complexes is discussed. A mechanism for autocatalytic oxidation of Cu(I)-thiolates promoted by a growing electronically coupled -[CuI2(RSSR)]n- polymer is suggested. The obtained results are in line with other reported observations regarding copper-catalyzed autoxidation of thiols and provide new insight into these complicated, not yet fully understood systems. The proposed hypotheses point to the importance of the Cu(I)-disulfide interaction, which may have a profound impact on biological systems.


Subject(s)
Acetylcysteine , Sulfhydryl Compounds , Antioxidants , Copper/chemistry , Disulfides , Oxidation-Reduction , Oxygen/chemistry , Reactive Oxygen Species
16.
Int J Mol Sci ; 23(11)2022 May 25.
Article in English | MEDLINE | ID: covidwho-1892893

ABSTRACT

Malaria is an infectious disease and a serious public health problem in the world, with 3.3 billion people in endemic areas in 100 countries and about 200 million new cases each year, resulting in almost 1 million deaths in 2018. Although studies look for strategies to eradicate malaria, it is necessary to know more about its pathophysiology to understand the underlying mechanisms involved, particularly the redox balance, to guarantee success in combating this disease. In this review, we addressed the involvement of oxidative stress in malaria and the potential benefits of antioxidant supplementation as an adjuvant antimalarial therapy.


Subject(s)
Antimalarials , Malaria , Antimalarials/pharmacology , Antimalarials/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Humans , Malaria/drug therapy , Oxidation-Reduction , Oxidative Stress
17.
Int J Environ Res Public Health ; 19(11)2022 06 03.
Article in English | MEDLINE | ID: covidwho-1892883

ABSTRACT

In this study, the removal of persistent emerging and dangerous pollutants (pharmaceuticals and pathogens) in synthetic wastewater was evaluated by the application of heterogeneous Advanced Oxidation Processes. To do that, a Metal-Organic Framework (MOF), Basolite® F-300 was selected as a catalyst and combined with peroxymonosulfate (PMS) as oxidants in order to generate sulphate radicals. Several key parameters such as the PMS and Basolite® F-300 concentration were evaluated and optimized using a Central Composite Experimental Design for response surface methodology for the inactivation of Escherichia coli. The assessment of the degradation of an analgesic and antipyretic pharmaceutical, antipyrine, revealed that is necessary to increase the concentration of PMS and amount of Basolite® F-300, in order to diminish the treatment time. Finally, the PMS-Basolite® F-300 system can be used for at least four cycles without a reduction in its ability to disinfect and degrade persistent emerging and dangerous pollutants such as pharmaceuticals and pathogens.


Subject(s)
Disinfection , Water Pollutants, Chemical , Antipyrine , Escherichia coli , Oxidation-Reduction , Peroxides , Pharmaceutical Preparations , Water Pollutants, Chemical/analysis
18.
Redox Biol ; 54: 102362, 2022 08.
Article in English | MEDLINE | ID: covidwho-1882476

ABSTRACT

In blood, the majority of endothelial nitric oxide (NO) is scavenged by oxyhemoglobin, forming nitrate while a small part reacts with dissolved oxygen to nitrite; another fraction may bind to deoxyhemoglobin to generate nitrosylhemoglobin (HbNO) and/or react with a free cysteine to form a nitrosothiol. Circulating nitrite concentrations in healthy individuals are 200-700 nM, and can be even lower in patients with endothelial dysfunction. Those levels are similar to HbNO concentrations ([HbNO]) recently reported, whereby EPR-derived erythrocytic [HbNO] was lower in COVID-19 patients compared to uninfected subjects with similar cardiovascular risk load. We caution the values reported may not reflect true (patho)physiological concentrations but rather originate from complex chemical interactions of endogenous nitrite with hemoglobin and ascorbate/N-acetylcysteine. Using an orthogonal detection method, we find baseline [HbNO] to be in the single-digit nanomolar range; moreover, we find that these antioxidants, added to blood collection tubes to prevent degradation, artificially generate HbNO. Since circulating nitrite also varies with lifestyle, dietary habit and oral bacterial flora, [HbNO] may not reflect endothelial activity alone. Thus, its use as early marker of NO-dependent endothelial dysfunction to stratify COVID-19 patient risk may be premature. Moreover, oxidative stress not only impairs NO formation/bioavailability, but also shifts the chemical landscape into which NO is released, affecting its downstream metabolism. This compromises the endothelium's role as gatekeeper of tissue nutrient supply and modulator of blood cell function, challenging the body's ability to maintain redox balance. Further studies are warranted to clarify whether the nature of vascular dysfunction in COVID-19 is solely of endothelial nature or also includes altered erythrocyte function.


Subject(s)
COVID-19 , Nitrites , Electron Spin Resonance Spectroscopy , Endothelium/metabolism , Hemoglobins/metabolism , Humans , Nitric Oxide/metabolism , Nitrites/metabolism , Oxidation-Reduction , Translational Research, Biomedical
19.
Int J Mol Sci ; 22(19)2021 Sep 25.
Article in English | MEDLINE | ID: covidwho-1855648

ABSTRACT

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.


Subject(s)
Antioxidants/metabolism , Esterases/metabolism , Protein Transport/physiology , Serum Albumin/metabolism , Signal Transduction/physiology , Animals , Humans , Oxidation-Reduction
20.
Trends Biochem Sci ; 47(5): 372-374, 2022 05.
Article in English | MEDLINE | ID: covidwho-1821500

ABSTRACT

Modifications of cysteine residues in redox-sensitive proteins are key to redox signaling and stress response in all organisms. A novel type of redox switch was recently discovered that comprises lysine and cysteine residues covalently linked by an nitrogen-oxygen-sulfur (NOS) bridge. Here, we discuss chemical and biological implications of this discovery.


Subject(s)
Cysteine , Lysine , Cysteine/chemistry , Lysine/metabolism , Oxidation-Reduction , Oxidative Stress , Protein Processing, Post-Translational , Proteins/chemistry
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