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1.
Sci Rep ; 14(1): 18570, 2024 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-39127758

RESUMO

Three-finger proteins are the most abundant toxins in the venom of Naja ashei, a snake species from the Elapidae family. This research aimed to describe the effects of varying charges of these proteins, isolated from Naja ashei venom using SEC and IEX chromatography. The study examined how differently charged three-finger toxin fractions interact with and affect neuroblastoma (SK-N-SH) and promyeloblast (HL-60) cells, as well as model Langmuir membranes and liposomes designed to mimic cellular lipid composition. Findings revealed that protein surface charges significantly impact cell survival (MTT assay), membrane damage (lactate dehydrogenase release, malondialdehyde formation), and the structural and electrochemical properties of model membranes (Langmuir membranes and zeta potential for liposomes and cancer cell lines). Results indicated that SK-N-SH cells, characterized by a higher negative charge on their cell membranes, interacted more effectively with positively charged toxins than HL-60 cells. However, the mechanism of these electrostatic interactions is complex. The research demonstrated that electrostatic and mechanical membrane modifications induced by venom proteins can significantly affect cell metabolism. Additionally, the total charge of the membrane, influenced by polar lipid components and phospholipid saturation, plays a decisive role in toxin interaction.


Assuntos
Membrana Celular , Venenos Elapídicos , Humanos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Venenos Elapídicos/química , Animais , Naja , Linhagem Celular Tumoral , Células HL-60 , Sobrevivência Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Lipossomos/química , Neuroblastoma/patologia , Neuroblastoma/metabolismo
2.
Molecules ; 29(15)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39125033

RESUMO

The toxicity of silver nanoparticles (AgNPs) depends on their physicochemical properties. The ongoing research aims to develop effective methods for modifying AgNPs using molecules that enable control over the processes induced by nanoparticles in both normal and cancerous cells. Application of amino acid-stabilized nanoparticles appears promising, exhibiting tunable electrokinetic properties. Therefore, this study focused on determining the influence of the surface charge of cysteine (CYS)-stabilized AgNPs on their toxicity towards human normal B (COLO-720L) and T (HUT-78) lymphocyte cell lines. CYS-AgNPs were synthesized via the chemical reduction. Transmission electron microcopy (TEM) imaging revealed that they exhibited a quasi-spherical shape with an average size of 18 ± 3 nm. CYS-AgNPs remained stable under mild acidic (pH 4.0) and alkaline (7.4 and 9.0) conditions, with an isoelectric point observed at pH 5.1. Following a 24 h treatment of lymphocytes with CYS-AgNPs, concentration-dependent alterations in cell morphology were observed. Positively charged CYS-AgNPs notably decreased lymphocyte viability. Furthermore, they exhibited grater genotoxicity and more pronounced disruption of biological membranes compared to negatively charged CYZ-AgNPs. Despite both types of AgNPs interacting similarly with fetal bovine serum (FBS) and showing comparable profiles of silver ion release, the biological assays consistently revealed that the positively charged CYS-AgNPs exerted stronger effects at all investigated cellular levels. Although both types of CYS-AgNPs have the same chemical structure in their stabilizing layers, the pH-induced alterations in their surface charge significantly affect their biological activity.


Assuntos
Cisteína , Nanopartículas Metálicas , Prata , Prata/química , Cisteína/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Humanos , Sobrevivência Celular/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linhagem Celular , Propriedades de Superfície , Concentração de Íons de Hidrogênio , Tamanho da Partícula
3.
Sci Rep ; 14(1): 16636, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025941

RESUMO

In therapies, curcumin is now commonly formulated in liposomal form, administered through injections or creams. This enhances its concentration at the cellular level compared to its natural form ingestion. Due to its hydrophobic nature, curcumin is situated in the lipid part of the membrane, thereby modifying its properties and influencing processes The aim of the research was to investigate whether the toxicity of specific concentrations of curcumin, assessed through biochemical tests for the SK-N-SH and H-60 cell lines, is related to structural changes in the membranes of these cells, caused by the localization of curcumin in their hydrophobic regions. Biochemical tests were performed using spectrophotometric methods. Langmuir technique were used to evaluate the interaction of the curcumin with the studied lipids. Direct introduction of curcumin into the membranes alters their physicochemical parameters. The extent of these changes depends on the initial properties of the membrane. In the conducted research, it has been demonstrated that curcumin may exhibit toxicity to human cells. The mechanism of this toxicity is related to its localization in cell membranes, leading to their dysfunction. The sensitivity of cells to curcumin presence depends on the saturation level of their membranes; the more rigid the membrane, the lower the concentration of curcumin causes its disruption.


Assuntos
Membrana Celular , Curcumina , Neuroblastoma , Curcumina/farmacologia , Curcumina/química , Humanos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Linhagem Celular Tumoral , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Interações Hidrofóbicas e Hidrofílicas
4.
Int J Mol Sci ; 24(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38139005

RESUMO

Human immune cells possess the ability to react complexly and effectively after contact with microbial virulence factors, including those transported in cell-derived structures of nanometer sizes termed extracellular vesicles (EVs). EVs are produced by organisms of all kingdoms, including fungi pathogenic to humans. In this work, the immunomodulatory properties of EVs produced under oxidative stress conditions or at host concentrations of CO2 by the fungal pathogen Candida albicans were investigated. The interaction of EVs with human pro-monocytes of the U-937 cell line was established, and the most notable effect was attributed to oxidative stress-related EVs. The immunomodulatory potential of tested EVs against human THP-1 macrophages was verified using cytotoxicity assay, ROS-production assay, and the measurement of cytokine production. All fungal EVs tested did not show a significant cytotoxic effect on THP-1 cells, although a slight pro-oxidative impact was indicated for EVs released by C. albicans cells grown under oxidative stress. Furthermore, for all tested types of EVs, the pro-inflammatory properties related to increased IL-8 and TNF-α production and decreased IL-10 secretion were demonstrated, with the most significant effect observed for EVs released under oxidative stress conditions.


Assuntos
Citocinas , Vesículas Extracelulares , Humanos , Citocinas/metabolismo , Candida albicans/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Vesículas Extracelulares/metabolismo
5.
Int J Environ Health Res ; 32(4): 885-901, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32772735

RESUMO

Modern nanotechnology allows obtaining zinc oxide nanomaterials with unique properties that let its use in a wide range of commercial applications. Direct contact with these particles as well as their release into the environment is almost inevitable. This review aims to consider whether the toxicity of zinc oxide nanoparticles found in numerous test models is a real threat to humans and plants. Emerging reports indicated both the risks and benefits associated with the use of zinc oxide nanoparticles in a manner dependent on the concentration and a method of synthesis, as well as the tested object. The amounts needed to achieve the antibacterial activity of ZnO-NPs, and the reported amounts of these nanoparticles in consumer products are sufficient to have a negative impact on living organisms. The most sensitive to their action are human cells, and the mechanism of cytotoxicity is mainly associated with the formation of oxidative stress caused by the action of zinc ions. ZnO-NPs in small concentration can have positive affect to plants, but it poses a threat to more sensitive ones.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Humanos , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Nanotecnologia , Estresse Oxidativo , Óxido de Zinco/toxicidade
6.
J Appl Toxicol ; 42(4): 570-587, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34558088

RESUMO

Silver nanoparticles (AgNPs) prepared and stabilized by diverse biologically active substances seem to be especially useful in diverse biological and medical applications. The combination of AgNPs with bioactive substances, such as antioxidants, can lead to the development of new systems of desired anticancer properties. In this research, AgNPs were prepared with the use of diverse antioxidant combinations including gallic acid (GA), (-)-epicatechin-3-gallate (EGCG), and caffeine (CAF). The insightful physicochemical characteristic revealed that each type of AgNPs exhibited spherical shape, comparable size distribution and negative surface charge. Surface-enhanced Raman spectroscopy (SERS) delivered the information about the chemistry of AgNP stabilizing layers, which turned out to be a crucial factor tuning toxicity of AgNPs toward murine B16 melanoma cells (B16-F0) and human skin melanoma (COLO 679) cells. EGCGAgNPs were the most cytotoxic among all the investigated AgNPs. They strongly reduced the activity of mitochondria, damaged cell membrane integrity, and penetrated inside the cells causing DNA damage. In turn, the toxicity of GAAgNPs strongly manifested via the induction of oxidative stress in the cells. It was found that CAFGAAgNPs exhibited the lowest toxicity toward the melanoma cells, which proved that a proper combination of antioxidants enable to prepare AgNPs of differentiated toxicity. It was established that human skin melanoma cells were significantly more sensitive to AgNPs than the murine melanoma cells.


Assuntos
Antineoplásicos , Melanoma , Nanopartículas Metálicas , Animais , Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Humanos , Melanoma/tratamento farmacológico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Prata/química , Prata/toxicidade , Análise Espectral Raman
7.
J Appl Toxicol ; 42(2): 334-341, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34235764

RESUMO

Currently, we are dealing with ever-increasing pollution of the environment with metal and metal oxide nanoparticles. One type of these, zinc oxide nanoparticles (ZnO-NPs), are increasingly used in areas such as cosmetology, electrical engineering, medicine, and even in the food and textile industries. As a consequence, ZnO-NPs may enter the human body in many ways. Their influence on the body is still not clear. Here, we define the mechanism of the initial toxicity of ZnO-NPs to cells based on interaction with the lipid part of the native and model cell membrane. The selected cell lines react differently to contact with nanoparticles. We found a disruption of the native membranes of B16-F0 cells and to a lesser extent of COLO 679. In turn, the membrane of COLO 679 cells was more peroxidated, and cell viability was much lower. A model of the lipid part of the membrane was created for B16-F0 cells and compared with previously published studies on immune cells. On the basis of physicochemical parameters obtained for individual lipids and a mix representing the native membrane of the tested cells, we concluded that exposure to nanoparticles resulted in a change within the model membranes (specifically with the polar parts of lipids). The greatest interaction has been noticed between ZnO-NPs and zwitterionic phospholipids (PC and PE), cholesterol, and negatively charged phosphatidylglycerol. Assessing the interactions between the membrane and nanoparticles will help to better understand the first steps of its toxicity mechanism.


Assuntos
Membrana Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Óxido de Zinco/toxicidade , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
8.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443533

RESUMO

Quercetin is a polyphenolic compound, the effects of which raise scientists' doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).


Assuntos
Membrana Celular/efeitos dos fármacos , Neuroblastoma/patologia , Quercetina/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Ozônio/farmacologia , Pressão , Temperatura
9.
J Appl Toxicol ; 41(11): 1863-1878, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33881181

RESUMO

The properties of silver nanoparticles (AgNPs) synthesized using compounds exhibiting biological activity seem to constitute an interesting issue worthy of examination. In these studies, two types of AgNPs were synthesized by a chemical reduction method using well-known antioxidants: gallic acid (GA) and ascorbic acid (AA). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the AgNPs were spherical. The average size was equal to 26 ± 6 nm and 20 ± 7 nm in the case of ascorbic acid-silver nanoparticles (AAgNPs) and gallic acid-silver nanoparticles (GAAgNPs), respectively. Surface-enhanced Raman spectroscopy (SERS) confirmed that the AgNPs were not stabilized by pure forms of applied antioxidants. Changes in mitochondrial activity and secretion of inflammatory and apoptosis mediators after the exposure of human promyelocytic (HL-60) and histiocytic lymphoma (U-937) cells to the AgNPs were studied to determine the impact of stabilizing layers on nanoparticle toxicity. The GAAgNPs were found to be more toxic for the cells than the AAgNPs. Their toxicity was manifested by a strong reduction in mitochondrial activity and induction of the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-9. The addition of pure antioxidants to the AgNP suspensions was found to influence their toxicity. There was a significant positive effect in the case of the mixture of AA with AAgNPs and GA with GAAgNPs. The results obtained suggest that the presence of stabilizing agents adsorbed on the surface of AgNPs is the main factor in shaping their toxicity. Nevertheless, the toxic effect can be also tuned by the introduction of free antioxidant molecules to the AgNP suspensions.


Assuntos
Antioxidantes/metabolismo , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Células HL-60 , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Prata/química , Análise Espectral Raman , Células U937
10.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918763

RESUMO

Three-finger toxins are naturally occurring proteins in Elapidae snake venoms. Nowadays, they are gaining popularity because of their therapeutic potential. On the other hand, these proteins may cause undesirable reactions inside the body's cells. A full assessment of the safety of Naja ashei venom components for human cell application is still unknown. The aim of the study was to determine the effect of the exogenous application of three-finger toxins on the cells of monocytes (U-937) and promyelocytes (HL-60), with particular emphasis on the modification of their membranes under the influence of various doses of 3FTx protein fraction (0-120 ng/mL). The fraction exhibiting the highest proportion of 3FTx proteins after size exclusion chromatography (SEC) separation was used in the experiments. The structural response of cell membranes was described on the basis of single-component and multi-component Langmuir monolayers that mimicked the native membranes. The results show that the mechanism of protein-lipid interactions depends on both the presence of lipid polar parts (especially zwitterionic type of lipids) and the degree of membrane saturation (the greatest-for unsaturated lipids). The biochemical indicators reflecting the tested cells (MDA, LDH, cell survival, induction of inflammation, LD50) proved the results that were obtained for the model.


Assuntos
Venenos Elapídicos/química , Venenos Elapídicos/toxicidade , Membranas Artificiais , Naja/metabolismo , Proteínas/toxicidade , Animais , Fracionamento Químico , Cromatografia em Gel , Feminino , Células HL-60 , Humanos , L-Lactato Desidrogenase/metabolismo , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Membranas , Pressão , Temperatura , Células U937
11.
Colloids Surf B Biointerfaces ; 200: 111593, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33540348

RESUMO

In this work, we clearly focus on the comparative cytotoxicity investigations of several protein-stabilized gold nanoclusters (Au NCs) towards lymphocytes B (COLO-720 L) and lymphocytes T (HUT-78) cells. For synthesis, the one-pot template-assisted method was carried out using lysozyme (LYZ), human (HSA) and bovine (BSA) serum albumins, and gamma globulin (γG) as stabilizing agents. Regardless of the type of proteins, all synthesized Au NCs possess intense red emission (λem ∼ 650 nm) and have similar size of a metal core (ca. 1.4 nm) with negative surface charge at pH = 7.4. During the treatment of cells with clusters, changes in mitochondrial activity, membrane integrity, secretion of inflammatory and apoptosis mediators of the lymphocytes were studied to determine the potential effect of protein layers on the toxicity of clusters. It was found that γG-Au NCs induced the highest disorders in mitochondrial activity, but the influence of other NCs on the cell viability was minor. Besides, all Au NCs caused oxidative stress by peroxidation of membrane lipids. The secretion of malonic dialdehyde (MDA) was enhanced by LYZ- and γG-Au NCs. Apart from LYZ-Au NCs, the clusters did not exhibit strong proinflammatory and apoptotic properties. The enhanced secretion of tumor necrosis factor (TNF-α) by lymphocytes B, in comparison to control, was independent of the clusters type. Despite the lack of significant influence of the Au NCs on the viability of the lymphocytes, they can stimulate undesirable cellular processes, which clearly depends on the stabilizing proteins.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Bovinos , Sobrevivência Celular , Corantes , Corantes Fluorescentes , Humanos , Linfócitos , Nanopartículas Metálicas/toxicidade
12.
J Appl Toxicol ; 41(3): 458-469, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33103261

RESUMO

The development of nanotechnology has led to the increased production of zinc oxide nanoparticles (ZnO-NPs) and their application in a wide variety of everyday products. It creates the need for a full assessment of their safety for humans. The aim of the study was to assess the toxic effects of ZnO-NPs on model human cells of the immune system: U-937, HL-60, HUT-78, and COLO-720L. Particular attention was paid to the direct interaction of the nanoparticles with membrane lipids and the role of zinc ions in the mechanism of their toxicity. Cell viability, lipid peroxidation, cell membrane integrity, and the amount of zinc ions released from nanoparticles were tested. Disruption in cell metabolism was noted for ZnO-NPs concentrations from 6.25 mg/L. Contact with ZnO-NPs caused lipid peroxidation of all cells and correlated with membrane disruption of HL-60, HUT-78, and COLO-720L cells. Model monolayers (Langmuir technique) were used to assess the interaction of the nanoparticles with the studied lipids. Physicochemical parameters, such as the area per molecule at maximal layer compression, the pressure at which the monolayer collapses, and the static compression modulus, were calculated. The models of the HL-60 and U-937 cell membranes under ZnO-NPs treatment reacted in a different way. It has also been shown that Zn2+ are not the main causative factor of ZnO-NPs toxicity. Investigating the early stages of mechanism of nanoparticles toxicity will allow for a more complete risk assessment and development of methods for a safer synthesis of engineering nanomaterials.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Óxido de Zinco/toxicidade , Humanos
13.
J Appl Toxicol ; 41(9): 1425-1437, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33368402

RESUMO

Zinc oxide nanoparticles (ZnO-NPs) are widely used in almost every area of life. Therefore, exposure to them is unavoidable, which makes it necessary to assess their safety for humans. This paper aims to determine toxicity of ZnO-NPs of two diameters toward human immune cells responsible for: innate response (U-937 and HL-60) and acquired response (COLO-720L and HUT-78). Mitochondrial activity, membrane integrity, degree of cellular lipid oxidation, induction of inflammation, and activation of the apoptosis pathway were evaluated to determine differences in cellular response to the tested nanoparticles. ZnO-NPs with a diameter of 100 and 130 nm cause significant cell mortality at 25 and 12 mg/L, respectively. Mitochondrial damage leads to the activation of the caspase cascade and, consequently, to cell apoptosis. ZnO-NPs also cause peroxidation of membrane lipids. Due to the photocatalytic properties of ZnO-NPs, the effect of ultraviolet (UV) irradiation on the degree of their toxicity was also investigated. However, UV irradiation enhances the toxic effect of nanoparticles mainly by weakening the cell's defense capabilities. ZnO-NPs are cytotoxic to human immune system, and they may cause both long-term and short-term negative effects.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Óxido de Zinco/toxicidade , Imunidade Adaptativa/efeitos da radiação , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/patologia , Humanos , Imunidade Celular/efeitos da radiação , Imunidade Inata/efeitos da radiação , Inflamação/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta
14.
J Environ Sci Health B ; 55(8): 719-725, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538258

RESUMO

The industrialization of the agricultural sector has significantly increased the use of chemicals such as pesticides. Therefore, exposure to them is unavoidable, which makes it necessary to assess their safety for humans at actual exposure doses. This paper aims to determine toxicity of three types of pesticides toward human immune cells (HL-60 and U-937): glyphosate (GLY), deltamethrin (DEL), and chlorothalonil (CHL). Cell viability, membrane integrity, inflammation induction, and antioxidant activity were evaluated to determine differences in cellular response to the tested plant protection agents. In experimental models, all tested substances caused increased mortality of cells after only 24 h. Cell membrane damage was recorded under DEL and CHL influences. The largest disintegration of the cell membrane was due to the action of 100 µg/mL DEL for U-937 and CHL at 1 µg/mL for HL-60. GLY at a concentration of 3,600 µg/mL caused significant peroxidation of U-937 cells' lipids. CHL-induced inflammation in both types of cells tested. DEL and GLY also induced antioxidant activity in cells. These results lead to the conclusion that the tested pesticides act cytotoxically to the cells of the human immune system in doses to which both farmers and consumers are exposed.


Assuntos
Glicina/análogos & derivados , Sistema Imunitário/efeitos dos fármacos , Nitrilas/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Agricultura , Antioxidantes/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Fazendeiros , Glicina/toxicidade , Células HL-60 , Humanos , Sistema Imunitário/citologia , Peroxidação de Lipídeos/efeitos dos fármacos , Exposição Ocupacional , Testes de Toxicidade , Glifosato
15.
Acta Biochim Pol ; 66(3): 365-370, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31531419

RESUMO

Effect of metal oxide nanoparticles on calli of two wheat varieties: Parabola (stress tolerant) and Raweta (sensitive) was studied. ZnO induced 10% larger membrane damage in Raweta calli. TiO2, Al2O3, and ZrO2 caused nearly 30% greater lactate dehydrogenase leakage for Raweta compared to Parabola. UV-irradiation of samples containing ZnO particles intensified this effect. Membrane lipid peroxidation in ZnO treated Raweta calli was twice as high as in Parabola and further increased after UV-irradiation. TiO2, Al2O3, and ZrO2 nanoparticles caused a 4-fold increase in malondialdehyde concentration in Raweta calli in comparison to Parabola calli. The nanoparticles studied damaged the cellular defense system by inactivating the antioxidative enzymes.


Assuntos
Óxido de Alumínio/toxicidade , Nanopartículas Metálicas/química , Titânio/toxicidade , Triticum/efeitos dos fármacos , Óxido de Zinco/toxicidade , Zircônio/toxicidade , Óxido de Alumínio/química , Membrana Celular/metabolismo , Sobrevivência Celular , Proteção de Cultivos/métodos , L-Lactato Desidrogenase/antagonistas & inibidores , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Lipídeos de Membrana/química , Estresse Oxidativo , Tamanho da Partícula , Peroxidase/antagonistas & inibidores , Células Vegetais/efeitos dos fármacos , Células Vegetais/metabolismo , Células Vegetais/efeitos da radiação , Superóxido Dismutase/antagonistas & inibidores , Titânio/química , Triticum/citologia , Triticum/enzimologia , Raios Ultravioleta/efeitos adversos , Óxido de Zinco/química , Zircônio/química
16.
RSC Adv ; 9(67): 39367-39380, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-35540630

RESUMO

Here we report studies on the synthesis of 12 new heterocyclic derivatives that differ in three structural motifs and the simultaneous evaluation of the impact of these three variables on the biological properties. The examined compounds are based on rhodanine and 2-thiohydantoin cores equipped with hydrogen or carboxymethyl substituents at the N-3 position and linked to a triphenylamine moiety through 1,4-phenylene, 1,4-naphthalenylene and 1,9-anthracenylene spacers at the C-5 position of the heterocycles. All the compounds were synthesized very quickly, selectively and in high yields according to the developed microwave-assisted Knoevenagel condensation protocol, and they were characterized thoroughly with NMR, FT-IR and ESI-HRMS techniques. The derivatives were tested for their activity against selected strains of Gram-positive and Gram-negative bacteria and yeast. Two compounds showed good activity against Gram-positive bacteria, and all of them showed low cytotoxicity against three cell lines of the human immune system. Based on membrane permeability assays it was demonstrated that the active compounds do not penetrate the cell membrane, and thus they must act on the bacterial cell surface. Finally, we proved that the evaluated structure modifications had a synergistic effect and the simultaneous presence of a 1,4-phenylene spacer and carboxymethyl group at N-3 caused the highest boost in antimicrobial activity.

17.
Mycotoxin Res ; 35(1): 89-98, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30411199

RESUMO

The progressive contamination of food products by mycotoxins such as zearalenone (ZEN) has prompted the search for specific substances that can act as protectors against an accumulation of these toxins. This paper discusses the effect of selenium ions and 24-epibrassinolide (EBR) as non-organic and organic compounds that preserve human lymphoblastic cells U-937 under ZEN stressogenic conditions. Based on measurements of cell viability and a DAPI test, concentrations of ZEN at 30 µmol/l, Se at 2.5 µmol/l and EBR at 0.005 µmol/l were selected. The addition of both protectors resulted in an increase in the viability of ZEN-treated cells by about 16%. This effect was connected with a decrease in lipid peroxidation (a decrease in the malonyldialdehyde content) and the generation of reactive oxygen species, which were determined by a cellular ROS/superoxide detection assay and the SOD activity. The Se protection was observed as the blocking of the all excess ROS, while the EBR action was mainly concentrated on something other than the superoxide radical itself. The experiments on the model lipid membranes that mimic the environment of U-937 cells confirmed the affect of ZEN on the structure and physicochemical properties of human membranes. Although the presence of both Se and EBR reduced the effect of ZEN by blocking its interaction with a membrane, the action of Se was more evident.


Assuntos
Brassinosteroides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Micotoxinas/farmacologia , Selênio/farmacologia , Esteroides Heterocíclicos/farmacologia , Brassinosteroides/química , Membrana Celular , Fragmentação do DNA , Humanos , Íons , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Esteroides Heterocíclicos/química , Células U937
18.
Colloids Surf B Biointerfaces ; 160: 429-437, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28987952

RESUMO

The preparation of stable cysteine-capped silver nanoparticles (AgNPs), via the reduction of silver ions with sodium borohydride and modification of formed nanoparticles by l-cysteine, was developed. The micrographs from transmission electron microscopy (TEM) revealed that the spherical AgNPs exhibited an average size equal to 22±4nm. Surface enhanced Raman spectroscopy (SERS) and inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed a chemisorption of cysteine molecules on the AgNPs. Additionally, dynamic light scattering (DLS) measurements showed that the AgNPs were stable for ionic strength lower than 5×10-3molL-1 and at 6.8

Assuntos
Cisteína/química , Nanopartículas Metálicas/química , Prata/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Células HL-60 , Humanos , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Concentração Osmolar , Oxirredução/efeitos dos fármacos , Prata/farmacologia , Células U937
19.
Colloids Surf B Biointerfaces ; 156: 397-404, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28551574

RESUMO

The toxicity of three types of silver nanoparticles towards histiocytic lymphoma (U-937) and human promyelocytic cells (HL-60) was studied. The nanoparticles were synthesized in a chemical reduction method using sodium borohydride. Trisodium citrate and cysteamine hydrochloride were used to generate a negative and positive nanoparticle surface charge. The evaluation of cell viability, membrane integrity, antioxidant activity and the induction of inflammation were used to evaluate the difference in cellular response to the nanoparticle treatment. The results revealed that the cysteamine-stabilized (positively charged) nanoparticles (SBATE) were the least toxic although they exhibited a similar ion release profile as the unmodified (negatively charged) nanoparticles obtained using sodium borohydride (SBNM). Citrate-stabilized nanoparticles (SBTC) induced superoxide dismutase (SOD) activity in the HL-60 cells and total antioxidant activity in the U-937 cells despite their resistance to oxidative dissolution. The toxicity of SBNM nanoparticles was manifested in the disruption of membrane integrity, decrease in the mitochondrial functions of cells and the induction of inflammation. These findings allowed to conclude that mechanism of silver nanoparticle cytotoxicity is the combination of effects coming from the surface charge of nanoparticles, released silver ions and biological activity of stabilizing agent molecules.


Assuntos
Antioxidantes/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Prata/farmacologia , Antioxidantes/química , Antioxidantes/toxicidade , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HL-60 , Humanos , Concentração de Íons de Hidrogênio , Óxido Nítrico/biossíntese , Prata/química , Prata/toxicidade , Relação Estrutura-Atividade , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Células U937
20.
Toxicol Mech Methods ; 27(1): 58-71, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27780388

RESUMO

The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO3, CH3COOAg and AgClO4) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60. For both cell lines, silver salts are more toxic than the corresponding nanoparticles. Cell viability after treatment with the two forms of silver (salt/particle) is dependent on silver dose and degree of cells differentiation. Addition of the silver salt of doses greater than 5 mg/L results in decreased cell viability by over 60%, whereas nanoparticles' addition reduces cell viability on average by 30%. On the basis of the determined LD50 values it can be stated that for the tested cells the most toxic are AgClO4 and TAC. Production of nitric oxide, which is a mediator of inflammation, is the greatest after treatment of the cells by TAC. Different interactions of studied nanoparticles with albumin has been found and it was shown that addition of albumin to the cells treated by nanoparticles reduces their toxic effects. Obtained by us highly purified, mono-disperse AgNPs exhibit diverse effects relative to the biological systems, depending on the precursor salt used.


Assuntos
Acetatos/toxicidade , Nanopartículas Metálicas/toxicidade , Percloratos/toxicidade , Compostos de Prata/toxicidade , Nitrato de Prata/toxicidade , Prata/toxicidade , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células HL-60 , Humanos , Dose Letal Mediana , Nanopartículas Metálicas/química , Óxido Nítrico/imunologia , Prata/química , Propriedades de Superfície , Células U937
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