Examinando por Autor "Madrid, Yolanda"

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Ability of selenium species to inhibit metal-induced Aβ aggregation involved in the development of Alzheimer’s disease
(Springer, 2020-04-22) Vicente-Zurdo, David; Romero-Sánchez, Iván; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Extracellular accumulation of amyloid beta peptide (Aβ) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer’s disease (AD). Metals could induce Aβ aggregation, by their redox activity or binding properties to amyloid β fibrils, leading to their accumulation and deposition outside neurons. For this reason, metal chelation may have an acknowledged part to play in AD prevention and treatment. In the current work, the role of different selenium species, including selenium nanoparticles, in Aβ aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Aβ1–42 aggregation fibrils and to disaggregate them once formed. Transition biometals such as Fe(II), Cu(II), and Zn(II) at 50 μM were selected to establish the in vitro models. The DPPH assay was used to determine the antioxidant capacity of the evaluated selenium species. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) and with both chitosan and chlorogenic acid polyphenol (CGA@ChSeNPs) showed the highest antioxidant properties with EC50 of 0.9 and 0.07 mM, respectively. UV–Vis and d1(UV–Vis) spectra also revealed that selenium species, in particular selenomethionine (SeMet), were able to interact with metals. Regarding Aβ1–42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Aβ aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Aβ aggregation, as well as a high disaggregation capacity of Aβ fibrils in both the presence and absence of biometals, in addition to reducing the length and width (20% of reduction in the presence of Zn(II)) of the generated Aβ fibrils
Cytotoxicity, uptake and accumulation of selenium nanoparticles and other selenium species in neuroblastoma cell lines related to Alzheimer's disease by using cytotoxicity assays, TEM and single cell-ICP-MS
(Elsevier, 2023-04-08) Vicente-Zurdo, David; Gómez-Gómez, Beatriz; Romero-Sánchez, Iván; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, representing 80% of the total dementia cases. The “amyloid cascade hypothesis” stablishes that the aggregation of the beta-amyloid protein (Aβ42) is the first event that subsequently triggers AD development. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) have demonstrated excellent anti-amyloidogenic properties in previous works, leading to an improvement of AD aetiology. Here, the in vitro effect of selenium species in AD model cell line has been study to obtain a better assessment of their effects in AD treatment. For this purpose, mouse neuroblastoma (Neuro-2a) and human neuroblastoma (SH-SY5Y) cell lines were used. Cytotoxicity of selenium species, such as selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys) and Ch-SeNPs, has been determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry methods. Intracellular localisation of Ch-SeNPs, and their pathway through SH-SY5Y cell line, have been evaluated by transmission electron microscopy (TEM). The uptake and accumulation of selenium species by both neuroblastoma cell lines have been quantified at single cell level by single cell- Inductively Coupled Plasma with Mass Spectrometry detection (SC-ICP-MS), with a previous optimisation of transport efficiency using gold nanoparticles (AuNPs) ((69 ± 3) %) and 2.5 mm calibration beads ((92 ± 8) %). Results showed that Ch-SeNPs would be more readily accumulated by both cell lines than organic species being accumulation ranges between 1.2 and 89.5 fg Se cell−1 for Neuro-2a and 3.1–129.8 fg Se cell−1 for SH-SY5Y exposed to 250 μM Ch-SeNPs. Data obtained were statistically treated using chemometric tools. These results provide an important insight into the interaction of Ch-SeNPs with neuronal cells, which could support their potential use in AD treatment
Impact of fish growing conditions and cooking methods on selenium species in swordfish and salmon fillets
(Elsevier, 2019-10) Vicente-Zurdo, David; Gómez-Gómez, Beatriz; Pérez-Corona, María Teresa; Madrid, Yolanda
This study evaluates the effect of fish growing conditions (captured fisheries or aquaculture) and cooking methods (fried, oven-baked and smoked) on selenium species distribution in fish fillets (salmon and swordfish). Fillets from 10 individual fishes for each fish species were analyzed. Selenium speciation was examined using HPLC–ICP–MS. Selenium in fillet samples was mainly present as organic selenium (around 93% of selenium content). Selenomethionine (SeMet) and selenocystine (SeCys2) were the main species found in salmon, regardless of its growing conditions (farmed or wild). However, SeCys2 was found at a higher concentration in wild salmon fillets. Concerning swordfish, SeMet, SeCys2 and selenomethylselenocysteine (SeMetSeCys) were detected and quantified. New selenium species were not produced when fillets were cooked. However, differences in selenium species distribution were observed for some fishes and/or treatments. Baking led to a notable increase of SeMetSeCys in swordfish (68% of the total selenium), in comparison with the amount of SeMetSeCys found in raw fish (17% of total selenium), whereas a notable decrease of SeCys2 occurred when salmon was submitted to the different cooking techniques. In contrast, smoked salmon provided a selenium species distribution similar to that of raw farmed salmon.
Neuroprotective activity of selenium nanoparticles against the effect of amino acid enantiomers in Alzheimer’s disease
(Springer, 2022-08-19) Vicente-Zurdo, David; Rodríguez-Blázquez, Sandra; Gómez-Mejía, Esther; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Alzheimer’s disease (AD), the most prevalent neurodegenerative disease, is characterized by extracellular accumulation of amyloid-beta protein (Aβ), which is believed to be the very starting event of AD neurodegeneration. In this work, D-Phe, D-Ala, and D-Glu amino acids, which are the non-occurring enantiomeric form in the human body, and also D-Asp and DL-SeMet, have proved to be amyloidogenic regarding Aβ42 aggregation in TEM studies. These amyloidogenic amino acid enantiomers also widened Aβ42 fibrils up to 437% regarding Aβ42 alone, suggesting that Aβ42 aggregation is enantiomerically dependent. To inhibit enantiomeric-induced amyloid aggregation, selenium nanoparticles stabilized with chitosan (Ch-SeNPs) were successfully synthesized and employed. Thus, Ch-SeNPs reduced and even completely inhibited Aβ42 aggregation produced in the presence of some amino acid enantiomers. In addition, through UV–Vis spectroscopy and fluorescence studies, it was deduced that Ch-SeNPs were able to interact differently with amino acids depending on their enantiomeric form. On the other hand, antioxidant properties of amino acid enantiomers were evaluated by DPPH and TBARS assays, with Tyr enantiomers being the only ones showing antioxidant effect. All spectroscopic data were statistically analysed through experimental design and response surface analysis, showing that the interaction between the Ch-SeNPs and the amino acids studied was enantioselective and allowing, in some cases, to establish the concentration ratios in which this interaction is maximum
Novel Rivastigmine Derivatives as Promising Multi‐Target Compounds for Potential Treatment of Alzheimer’s Disease
(MDPI, 2022-06-26) Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia; Brunetti, Leonardo; Piemontese, Luca; Raquel Pereira-Santos, A; Cardoso, Sandra M; Madrid, Yolanda; Chaves, Sílvia; Santos, M. Amélia
Alzheimer’s disease (AD) is the most serious and prevalent neurodegenerative disorder still without cure. Since its aetiology is diverse, recent research on anti‐AD drugs has been focused on multi‐target compounds. In this work, seven novel hybrids (RIV–BIM) conjugating the active moiety of the drug rivastigmine (RIV) with 2 isomeric hydroxyphenylbenzimidazole (BIM) units were developed and studied. While RIV assures the inhibition of cholinesterases, BIM provides further appropriate properties, such as inhibition of amyloid β‐peptide (Aβ) aggregation, antioxidation and metal chelation. The evaluated biological properties of these hybrids included antioxidant activity; inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and Aβ42 aggregation; as well as promotion of cell viability and neuroprotection. All the compounds are better inhibitors of AChE than rivastigmine (IC50 = 32.1 μM), but compounds of series 5 are better inhibitors of BChE (IC50 = 0.9−1.7 μM) than those of series 4. Series 5 also showed good capacity to inhibit self‐ (42.1−58.7%) and Cu(II)‐induced (40.3−60.8%) Aβ aggregation and also to narrow (22.4−42.6%) amyloid fibrils, the relevant compounds being 5b and 5d. Some of these compounds can also prevent the toxicity induced in SH‐SY5Y cells by Aβ42 and oxidative stress. Therefore, RIV– BIM hybrids seem to be potential drug candidates for AD with multi‐target abilities.
Rivastigmine–Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Compounds for Potential Treatment of Neurodegenerative Diseases
(MDPI, 2023-05-05) Vicente-Zurdo, David; Brunetti, Leonardo; Piemontese, Luca; Guedes, Beatriz; Cardoso, Sandra M; Chavarria, Daniel; Borges, Fernanda; Madrid, Yolanda; Chaves, Sílvia; Santos, M. Amélia
With the goal of combating the multi-faceted Alzheimer’s disease (AD), a series of Rivastigmine-Benzimidazole (RIV–BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-β (Aβ) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson’s disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the Aβ-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent
Screening the extraction process of phenolic compounds from pressed grape seed residue: Towards an integrated and sustainable management of viticultural waste
(Elsevier, 2022-11-01) Gómez-Mejía, Esther; Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
The integrated valorisation of waste from the food chain to obtain value-added compounds with biological functionality will facilitate the transition to the era of a sustainable bioeconomy. To this end, an efficient matrix solid-phase dispersion (MSPD) extraction method was developed and optimized, using experimental factorial design and response surface methodology, for polyphenols recovery from pressed grape seeds obtained after the extraction of essential oils by cold pressing. Gallic, dihydroxybenzoic, p-coumaric and trans-ferulic acid, naringin, resveratrol, quercetin and kaempferol were quantified at 2.1–295 μg g−1 by capillary liquid chromatography coupled to a diode array detector and a mass analyser (cLC-DAD-MS). Furthermore, total antioxidant activity, free radical scavenging and lipid peroxidation suppression, together with the inhibition of beta-amyloid (Αβ42) protein aggregation, considered one of the main pathological effects of Alzheimer's disease, were evaluated. Potent lipid peroxidation inhibition (IC50 0.238 ± 0.003 ng g−1) was observed, along with the reduction of Αβ42 fibril width (9.4–54.8%) and aggregation. The results presented proved that the MSPD extraction method could be considered as an efficient and sustainable methodology to produce phenolic-rich extracts that may serve as an alternative antioxidant and neuroprotective ingredient for the food or pharmaceutical formulations, leading to the cascade valorisation of winery by-products.
Selenium and mercury concentration in drinking water and food samples from a coal mining area in Brazil
(Springer, 2019-04-02) dos Santos, Marina; da Silva Júnior, Flavio Manoel Rodrigues; Vicente-Zurdo, David; Baisch, Paulo Roberto Martins; Muccillo-Baisch, Ana Luíza; Madrid, Yolanda
Selenium (Se) is an essential element for human health and can also alleviate the toxicity of elements such as mercury (Hg), which is considered deleterious to health. The study area is an important coal mineral region in Brazil, generating 40% of all Brazilian coal. During the coal mining process, Se and Hg are released, which can induce potential human health risks via the food chain. The purpose of the present study is to determine total Se and its species and total Hg in drinking water and food locally produced from a coal mining area, to assess the impact of coal mining. The samples were collected in two cities, with and without coal mining influence. Total Se levels in drinking water and food were assessed by inductively coupled plasma mass spectrometry (ICP-MS) and its species by high-performance liquid-ICP-MS, while total Hg was determined by cold vapor atomic fluorescence spectrometry. Drinking water (1.1 ± 0.2 mg L−1 dry weight) (p = 0.02) and tomatoes (1.5 ± 0.1 mg kg−1 dry weight) (p = 0.01) from the coal mining area had higher total Se concentration than the control area. The highest Se concentrations were found in animal-based food (6.4 ± 0.8 mg kg−1 dry weight) with an important contribution of Se IV (65%). The analyzed sample did not accumulate a significant amount of Hg. Future studies on the estimates of daily intake of these elements and dietary pattern of the population are needed to make appropriate dietary recommendations and support public health action
Single-cell ICP-MS for evaluating the Se-protective effect against MeHg+-induced neurotoxicity in human neuroblastoma cell line (SH-SY5Y)
(Springer, 2023-11-14) Fernández-Bautista, Tamara; Gómez-Gómez, Beatriz; Vicente-Zurdo, David; Madrid, Yolanda
The protective effect of selenium (Se) against Hg-induced neurotoxicity has been widely investigated; however, the mechanisms behind this interaction have not been fully elucidated yet. In the current work, the role of Se against MeHg+-induced cytotoxicity in the human neuroblastoma cell line (SH-SY5Y) is reported for the first time by tracking Hg uptake and accumulation at the single-cell level by inductively coupled plasma-mass spectrometry in single-cell mode (SC-ICP-MS). The influence of different Se species (SeMet, SeMeSeCys, citrate-SeNPs, and chitosan-SeNPs) on MeHg+ cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. SeMet and SeMeSeCys exhibited protective effects against MeHg+-induced cell death, particularly at high MeHg+ concentrations (LC50). In addition, chitosan-SeNPs showed greater protection compared to citrate-SeNPs when co-exposed with MeHg+. Interestingly, SC-ICP-MS unveiled the heterogeneous distribution of Hg uptake by SH-SY5Y cells. Co-exposure of SeMet and SeMeSeCys with MeHg+ led to a reduction of the amount of Hg accumulated per individual cell, which decreased the maximum level of Hg per cell by half (from 60 fg Hg cell−1 to 30 fg Hg cell−1) when SeMet was present, along with a decrease in the percentage of cells that accumulated the highest quantity of MeHg+. All these data corroborate the protective role of Se against Hg toxicity at the cellular level.