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1.
Eur J Med Chem ; 232: 114175, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35151223

RESUMEN

oxidative stress is caused by an abundant generation of reactive oxygen species, associated to a diminished capacity of the endogenous systems of the organism to counteract them. Activation of pro-oxidative pathways and boosting of inflammatory cytokines are always encountered in viral infections, including SARS-CoV-2. So, the importance of counteracting cytokine storm in COVID-19 pathology is highly important, to hamper the immunogenic damage of the endothelium and alveolar membranes. Antioxidants prevent oxidative processes, by impeding radical species generation. It has been proved that vitamin intake lowers oxidative stress markers, alleviates cytokine storm and has a potential role in reducing disease severity, by lowering pro-inflammatory cytokines, hampering hyperinflammation and organ failure. For the approached compounds, direct antiviral roles are also discussed in this review, as these activities encompass secretion of antiviral peptides, modulation of angiotensin-converting enzyme 2 receptor expression and interaction with spike protein, inactivation of furin protease, or inhibition of pathogen replication by nucleic acid impairment induction. Vitamin administration results in beneficial effects. Nevertheless, timing, dosage and mutual influences of these micronutrients should be carefullly regarded.


Asunto(s)
Antioxidantes , Tratamiento Farmacológico de COVID-19 , Antiinflamatorios , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , SARS-CoV-2 , Vitaminas/farmacología , Vitaminas/uso terapéutico
2.
Eur J Med Chem ; 209: 112891, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33032084

RESUMEN

The present review paper focuses on the chemistry of oxidative stress mitigation by antioxidants. Oxidative stress is understood as a lack of balance between the pro-oxidant and the antioxidant species. Reactive oxygen species in limited amounts are necessary for cell homeostasis and redox signaling. Excessive reactive oxygenated/nitrogenated species production, which counteracts the organism's defense systems, is known as oxidative stress. Sustained attack of endogenous and exogenous ROS results in conformational and oxidative alterations in key biomolecules. Chronic oxidative stress is associated with oxidative modifications occurring in key biomolecules: lipid peroxidation, protein carbonylation, carbonyl (aldehyde/ketone) adduct formation, nitration, sulfoxidation, DNA impairment such strand breaks or nucleobase oxidation. Oxidative stress is tightly linked to the development of cancer, diabetes, neurodegeneration, cardiovascular diseases, rheumatoid arthritis, kidney disease, eye disease. The deleterious action of reactive oxygenated species and their role in the onset and progression of pathologies are discussed. The results of oxidative attack become themselves sources of oxidative stress, becoming part of a vicious cycle that amplifies oxidative impairment. The term antioxidant refers to a compound that is able to impede or retard oxidation, acting at a lower concentration compared to that of the protected substrate. Antioxidant intervention against the radicalic lipid peroxidation can involve different mechanisms. Chain breaking antioxidants are called primary antioxidants, acting by scavenging radical species, converting them into more stable radicals or non-radical species. Secondary antioxidants quench singlet oxygen, decompose peroxides, chelate prooxidative metal ions, inhibit oxidative enzymes. Moreover, four reactivity-based lines of defense have been identified: preventative antioxidants, radical scavengers, repair antioxidants, and those relying on adaptation mechanisms. The specific mechanism of a series of endogenous and exogenous antioxidants in particular aspects of oxidative stress, is detailed. The final section resumes critical conclusions regarding antioxidant supplementation.


Asunto(s)
Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/química , Antioxidantes/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Oftalmopatías/tratamiento farmacológico , Oftalmopatías/metabolismo , Humanos , Enfermedades Renales/dietoterapia , Enfermedades Renales/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedades Vasculares/tratamiento farmacológico , Enfermedades Vasculares/metabolismo
3.
Beilstein J Org Chem ; 14: 2580-2588, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30410619

RESUMEN

Pseudomonas aeruginosa relies on the quorum sensing (QS) signaling system as a central regulator mechanism of virulence expression that contributes to the formation and maintenance of biofilms and tolerance to conventional antimicrobials. QS Signaling molecules (QSSMs) may be recognized and may function also within the host cells, being potentially involved in the progression of the infectious process. In this study we evaluate the expression of adhesion and inflammatory molecules in endothelial cells treated with P. aeruginosa QSSMs, in order to bring new insights on the mechanisms involved in the interaction of P. aeruginosa with host cells during the infectious process. Endothelial cells were stimulated with 20 µM of main P. aeruginosa QSSMs (OdDHL = N-(3-oxododecanoyl)-L-homoserine lactone, C4HSL = N-butyryl-L-homoserine lactone, PQS = 2-heptyl-3-hydroxy-4(1H)-quinolone and HHQ = 2-heptyl-4-quinolone). Adherence to endothelial cells, inert substratum and biofilm formation was evaluated. The expression of adhesion molecules (VE-cadherin, PECAM-1, ICAM-1, and P-selectin) and inflammatory response molecules (IL-1ß, IL-6, TNFα, TGFß, and eNOS) was assessed by qRT-PCR and flow cytometry. Our results showed that bacterial adherence to inert substratum and biofilm were decreased in the presence of all tested QSSMs. The adherence index of PAO1 laboratory strain to host cells was decreased between 10-40% in the presence of QSSMs, as compared to untreated control. Expression of eukaryotic cells adhesion molecules ICAM-1 and P-selectin was stimulated by QSSMs, whereas VE-cadherin and PECAM-1 levels were increased only by C4HSL. The inflammatory response of endothelial cells was also modulated, as observed by the modified expression of IL-1ß (for C4HSL, PQS and HHQ), IL-6 (for C4HSL and HHQ), TNFα (for C4HSL and HHQ), TGFß, and eNOS factors. Our results demonstrate that the main pseudomonadal QSSMs differentially modulate endothelial cells adhesion and proinflammatory cytokine expression. These observations provide new insights in the mechanisms by which different QSSMs activate endothelial cells and modulate the infectious process, and support the importance of recent studies aiming to develop anti-QS therapeutic strategies to fight against P. aeruginosa infections.

4.
Eur J Med Chem ; 157: 1326-1345, 2018 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-30196058

RESUMEN

Oxidative decay and microbial spoilage are issues of concern, as they constitute threats to human health. Natural antioxidants and antimicrobials hamper the negative impact of synthetic compounds and they need appropriate delivery systems. Different nanostructures can be developed: association colloids-based nanostructures, nanoemulsions, nanoliposomes, nanolaminates, nanofibers, carbon nanotubes, nanocomposites. The main nanoencapsulation techniques applied to antioxidants and antimicrobials are described: association colloid-based nanoincorporation, lipid-based nanoencapsulation techniques, encapsulation techniques based on biologically-derived polymeric nanocarriers, encapsulation techniques based on non-biological polymeric nanocarriers, cyclodextrin incorporation, electrospraying and electrospinning, carbon nanotubes and nanocomposite encapsulation. Several nanoencapsulation methods can be followed by freeze-drying or spray-drying. Protection of bioactive compounds and controlled release are achieved, but the impact of the nanomaterials on human health and on the environment should be considered. The influence of the nanoencapsulation techniques on the antioxidant/antimicrobial activity is discussed. The choice of the appropriate encapsulation method is vital. Bioactivity increase, preservation or decrease, depend on the interactions established between the functional groups of encapsulated compound and the encapsulating nanomaterial.


Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Nanoestructuras/química , Nanotecnología , Animales , Antibacterianos/química , Antioxidantes/química , Humanos
5.
Eur J Med Chem ; 143: 922-935, 2018 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-29227932

RESUMEN

The present paper aims to review the natural food preservatives with antimicrobial properties emphasizing their importance for the future of food manufacturing and consumers' health. The extraction procedures applied to natural antimicrobials will be considered, followed by the description of some natural preservatives' antimicrobial mechanism of action, including (i) membrane rupture with ATP-ase activity inhibition, (ii) leakage of essential biomolecules from the cell, (iii) disruption of the proton motive force and (iiii) enzyme inactivation. Moreover, a provenance-based classification of natural antimicrobials is discussed by considering the sources of origin for the major natural preservative categories: plants, animals, microbes and fungi. As well, the structure influence on the antimicrobial potential is considered. Natural preservatives could also constitute a viable alternative to address the critical problem of microbial resistance, and to hamper the negative side effects of some synthetic compounds, while meeting the requirements for food safety, and exerting no negative impact on nutritional and sensory attributes of foodstuffs.


Asunto(s)
Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Productos Biológicos/farmacología , Conservantes de Alimentos/farmacología , Hongos/efectos de los fármacos , Parásitos/efectos de los fármacos , Animales , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Conservantes de Alimentos/química , Conservantes de Alimentos/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Pruebas de Sensibilidad Parasitaria
6.
Oxid Med Cell Longev ; 2016: 9130976, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28044094

RESUMEN

The present paper aims at reviewing and commenting on the analytical methods applied to antioxidant and antioxidant capacity assessment in plant-derived products. Aspects related to oxidative stress, reactive oxidative species' influence on key biomolecules, and antioxidant benefits and modalities of action are discussed. Also, the oxidant-antioxidant balance is critically discussed. The conventional and nonconventional extraction procedures applied prior to analysis are also presented, as the extraction step is of pivotal importance for isolation and concentration of the compound(s) of interest before analysis. Then, the chromatographic, spectrometric, and electrochemical methods for antioxidant and antioxidant capacity determination in plant-derived products are detailed with respect to their principles, characteristics, and specific applications. Peculiarities related to the matrix characteristics and other factors influencing the method's performances are discussed. Health benefits of plants and derived products are described, as indicated in the original source. Finally, critical and conclusive aspects are given when it comes to the choice of a particular extraction procedure and detection method, which should consider the nature of the sample, prevalent antioxidant/antioxidant class, and the mechanism underlying each technique. Advantages and disadvantages are discussed for each method.


Asunto(s)
Antioxidantes/análisis , Fitoquímicos/análisis , Plantas/química , Métodos Analíticos de la Preparación de la Muestra , Antioxidantes/aislamiento & purificación , Extractos Vegetales/química
7.
Eur J Med Chem ; 97: 55-74, 2015 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-25942353

RESUMEN

This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.


Asunto(s)
Estrés Oxidativo , Especies Reactivas de Oxígeno/toxicidad , Antioxidantes/uso terapéutico , Humanos , Modelos Biológicos , Estrés Oxidativo/efectos de los fármacos
8.
Curr Pharm Biotechnol ; 16(2): 152-61, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25594291

RESUMEN

Antibiotic resistance is a major problem in current contemporary medicine and it has become a major concern of the 21st century. New resistance mechanisms developed by microorganisms spread greatly, threatening the ability to treat numerous infectious diseases, and increasing the number of nosocomial infections. Besides the role in immunology and glycobiology where they are used as hemaglutinine and identification of complex carbohydrates and glycoconjugates, lectins proved to mediate diversified biological functions like cytotoxicity, complement activation, cell-to-cell and host-pathogen communications, innate immune response, and cell-to-cell signalling. Recently, great interest has been developed for the research and applications of lectins in agriculture and medicine due to their antiparasitic and antimicrobial potentials. This review focuses on the recent data regarding the antimicrobial and antiparasitic activities of lectins, by presenting the role of lectins in host-pathogen interaction and also the cytotoxic effects on microorganisms and parasites. Identification and characterisation of new lectins with antimicrobial activity could serve as a natural alternative for the treatment of infections caused by antibiotic-resistant microorganisms and parasites.


Asunto(s)
Antiinfecciosos/farmacología , Lectinas/farmacología , Animales , Antiinfecciosos/uso terapéutico , Humanos , Lectinas/uso terapéutico
9.
Molecules ; 16(2): 1349-65, 2011 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-21285920

RESUMEN

A method was developed for assessing ascorbic acid concentration in fruit juices and wine by differential pulse voltammetry. The oxidation peak for ascorbic acid occurs at about 530 mV (versus SCE) on a Pt strip working electrode and at about 470 mV on a carbon paste working electrode. The influence of the operational parameters like the pulse amplitude and the pulse period on the analytical signal was investigated. The obtained calibration graph shows a linear dependence between the peak height and ascorbic acid concentration within the range 0.31-20 mM with a Pt working electrode, and within the range 0.07-20 mM with a carbon paste working electrode. The equation of the calibration graph was y = 21.839x + 35.726, r² = 0.9940, when a Pt strip electrode was used (where y represents the value of the current intensity measured for the peak height, expressed as µA and x the analyte concentration, as mM). R.S.D. = 2.09%, n = 10, C(ascorbic acid) = 2.5 mM. The equation of the calibration graph was y = 3.4429x + 5.7334, r² = 0.9971, when a carbon paste electrode was used (where y represents the value of intensity measured for the peak height, expressed as µA and x the analyte concentration, as mM). R.S.D. = 2.35%, n = 10, C(ascorbic acid) = 2.5 mM. The developed method was applied to ascorbic acid assessment in fruit juices and wine. The ascorbic acid content determined ranged between 6.83 mg/100 mL juice for soft drinks (Fanta Madness) and 54.74 mg/100 mL for citrus (lemon) juices obtained by squeezing fruit. Different ascorbic acid concentrations (from standard solutions) were added to the analysed samples, the degree of recovery being comprised between 94.74 and 104.97%. The results of ascorbic acid assessment by differential pulse voltammetry were compared with those obtained by cyclic voltammetry. The results obtained by the two methods were in good agreement.


Asunto(s)
Ácido Ascórbico/análisis , Bebidas/análisis , Carbono/química , Electroquímica/métodos , Electrodos , Frutas/química , Vino/análisis , Humanos , Platino (Metal)/química , Potenciometría/métodos
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