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1.
Front Mol Biosci ; 10: 1242935, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37954978

RESUMEN

Background: Strigolactones are signaling molecules produced by plants, the main functions are the intracorporeal control of plant development and plant growth. GR24 strigolactone is one of the synthetic strigolactones and due to its universality and easy availability, it is a standard and model compound for research on the properties and role of strigolactones in human health. Purpose: In this research work, the impact of mainly GR24 strigolactone on the human body and the role of this strigol-type lactone in many processes that take place within the human body are reviewed. Study design: The article is a review of publications on the use of GR24 strigolactone in studies from 2010-2023. Publications were searched using PubMed, Elsevier, Frontiers, and Springer databases. The Google Scholar search engine was also used. For the review original research papers and reviews related to the presented topic were selected. Results: The promising properties of GR24 and other strigolactone analogs in anti-cancer therapy are presented. Tumor development is associated with increased angiogenesis. Strigolactones have been shown to inhibit angiogenesis, which may enhance the anticancer effect of these γ-lactones. Furthermore, it has been shown that strigolactones have anti-inflammatory and antioxidant properties. There are also a few reports which show that the strigolactone analog may have antimicrobial and antiviral activity against human pathogens. Conclusion: When all of this is considered, strigolactones are molecules whose versatile action is their undeniable advantage. The development of research on these phytohormones makes it possible to discover their new, unique properties and surprising biological activities in relation to many mammalian cells.

2.
Int J Mol Sci ; 23(20)2022 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-36293241

RESUMEN

The effect of the interaction between fullerenol C60(OH)36 (FUL) and alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae and human serum albumin (HSA) was studied by absorption spectroscopy, fluorescence spectroscopy, and time-resolved fluorescence spectroscopy. As shown in the study, the fluorescence intensities of ADH and HSA at excitation wavelengths λex = 280 nm (Trp, Tyr) and λex = 295 nm (Trp) are decreased with the increase in the FUL concentration. The results of time-resolved measurements indicate that both quenching mechanisms, dynamic and static, are present. The binding constant Kb and the number of binding sites were obtained for HSA and ADH. Thus, the results indicated the formation of FUL complexes and proteins. However, the binding of FUL to HSA is much stronger than that of ADH. The transfer of energy from the protein to FUL was also proved.


Asunto(s)
Nanopartículas , Albúmina Sérica , Humanos , Albúmina Sérica/metabolismo , Alcohol Deshidrogenasa/metabolismo , Sitios de Unión , Espectrometría de Fluorescencia , Albúmina Sérica Humana/química , Unión Proteica , Termodinámica , Dicroismo Circular
3.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34361101

RESUMEN

Currently, carbon nanoparticles play a large role as carriers of various types of drugs, and also have applications in other fields of medicine, e.g., in tissue engineering, where they are used to reconstruct bone tissue. They also contribute to the early detection of cancer cells, and can act as markers in imaging diagnostics. Their antibacterial and anti-inflammatory properties are also known. This feature is particularly important in dental implantology, where various types of bacterial infections and implant rejection often occur. The search for newer and more effective treatments may lead to future use of nanoparticles on a large scale. In this work, the current state of knowledge on the possible use of nanotubes, nanodiamonds, and fullerenes in therapy is reviewed. Both advantages and disadvantages of the use of carbon nanoparticles in therapy and diagnostics have been indicated.


Asunto(s)
Antineoplásicos/administración & dosificación , Carbono/química , Sistemas de Liberación de Medicamentos , Nanomedicina , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Medicina Regenerativa , Animales , Antineoplásicos/química , Humanos , Nanopartículas/química
4.
Int J Mol Sci ; 22(9)2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33922469

RESUMEN

With the ongoing commercialization, human exposure to plastic nanoparticles will dramatically increase, and evaluation of their potential toxicity is essential. There is an ongoing discussion on the human health effects induced by plastic particles. For this reason, in our work, we assessed the effect of polystyrene nanoparticles (PS-NPs) of various diameters (29, 44 and 72 nm) on selected parameters of oxidative stress and the viability of human peripheral blood mononuclear cells (PBMCs) in the in vitro system. Cells were incubated with PS-NPs for 24 h in the concentration range of 0.001 to 100 µg/mL and then labeled: formation of reactive oxygen species (ROS) (including hydroxyl radical), protein and lipid oxidation and cell viability. We showed that PS-NPs disturbed the redox balance in PBMCs. They increased ROS levels and induced lipid and protein oxidation, and, finally, the tested nanoparticles induced a decrease in PBMCs viability. The earliest changes in the PBMCs were observed in cells incubated with the smallest PS-NPs, at a concentration of 0.01 µg/mL. A comparison of the action of the studied nanoparticles showed that PS-NPs (29 nm) exhibited a stronger oxidative potential in PBMCs. We concluded that the toxicity and oxidative properties of the PS-NPs examined depended to significant degree on their diameter.


Asunto(s)
Leucocitos Mononucleares/efectos de los fármacos , Nanopartículas/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Poliestirenos/química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Supervivencia Celular , Humanos , Leucocitos Mononucleares/patología , Nanopartículas/química
5.
Free Radic Biol Med ; 160: 734-744, 2020 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-32871231

RESUMEN

Polyhydroxylated fullerenes (fullerenols) are excellent free radical scavengers. Despite the large number of reports on their reactions with reactive oxygen species, there is no report on their ability to trap lipid peroxyl radicals and act as chain-breaking antioxidants. In this work we studied the effect of fullerenol C60(OH)36 on the kinetics of peroxidation of polyunsaturated fatty acid ester (methyl linoleate) dispersed in two model systems that mimic biological systems: Triton X-100 micelles and Large Unilamellar Vesicles, at pH 4, 7 and 10. As a control antioxidant 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC, an analog of α-tocopherol) was used. In micellar systems at pH 4.0, C60(OH)36 reacts with peroxyl radicals with kinh= (5.8 ± 0.3) × 103 M-1s-1 (for PMHC kinh = 22 × 103 M-1s-1). Surprisingly, at pH 7 a retardation instead of inhibition was recorded, and at pH 10 no effect on the kinetics of the process was observed. In liposomal systems fullerenol was not active at pH 4.0 but at pH 7.0 kinh = (8.8 ± 2.6) × 103 M-1s-1 for fullerenol was 30% lower than kinh for PMHC. Using two fluorescent probes we confirmed that at pH 7.4 fullerenol/fullerenol anions are incorporated into the phospholipid heads of the bilayer. We also studied the cooperation of C60(OH)36 with PMHC: both compounds seem to contribute their peroxyl radical trapping abilities independently at pH 4 whereas at pH 7 and 10 a hyper-synergy was observed. The antioxidant action of C60(OH)36 and its synergy with PMHC was also confirmed for peroxidation of human erythrocytes at pH 7.4. Assuming the simplified structural model of fullerenol limited to 36 hydroxyls as the only functional groups attached to C60 core we found by density-functional theory a low energy structure with OH groups distributed in the form of two polyhydroxyl regions separating two unsubstituted carbon regions with biphenyl-like structure. Our calculations indicate that abstraction of hydrogen atom from fullerenol by peroxyl or tocopheroxyl radical is endoergic. As the electron transfer from fullerenol polyanion to the radicals is also energetically disfavoured, the most probable mechanism of reaction with radicals is subsequent addition of peroxyl/tocopheroxyl radicals to biphenyl moieties surrounded by OH groups.


Asunto(s)
Antioxidantes , Fulerenos , Depuradores de Radicales Libres , Humanos , Peroxidación de Lípido , Liposomas , alfa-Tocoferol
6.
Int J Mol Sci ; 21(11)2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32486253

RESUMEN

Brominated flame retardants (BFRs) have been using to reduce the flammability of plastics contained in many products, such as household articles, furniture, mattresses, textiles or insulation. Considering the fact that these compounds may be released into the environment leading to the exposure of living organisms, it is necessary to study their possible effects and mechanisms of action. Proteins play a crucial role in all biological processes. For this reason, a simple model of human serum albumin (HSA) was chosen to study the mechanism of BFRs' effect on proteins. The study determined interactions between selected BFRs, i.e., tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP), and HSA by measurement of fluorescence of intrinsic tryptophan and absorbance of circular dichroism (CD). In addition, in order to understand the possible effect of these compounds in their native environment, the effect of BFRs on membrane proteins of human erythrocytes (red blood cells, RBCs) was also assessed. Among bromophenols, PBP had the strongest oxidative effect on RBC membrane, and 2,4-DBP demonstrated the weakest fluorescence-quenching effect of both membrane tryptophan and HSA. By contrast to PBP, 2,4-DBP and 2,4,6-TBP caused spatial changes of HSA. We have observed that among all analyzed BFRs, TBBPA caused the strongest oxidation of RBC membrane proteins and the model HSA protein, causing reduction of fluorescence of tryptophan contained in them. TBBPA also changed albumin conformation properties, leading to impairment of the α-helix structure. However, TBBPS had the weakest oxidative effect on proteins among studied BFRs and did not affect the secondary structure of HSA.


Asunto(s)
Bromo/efectos adversos , Membrana Eritrocítica/efectos de los fármacos , Retardadores de Llama/efectos adversos , Proteínas de la Membrana/química , Albúmina Sérica Humana/química , Bromo/química , Dicroismo Circular , Retardadores de Llama/clasificación , Fluorescencia , Halogenación , Humanos , Hidrocarburos Bromados/efectos adversos , Hidrocarburos Bromados/química , Oxidantes/efectos adversos , Oxidantes/química , Oxígeno/química , Fenoles/efectos adversos , Fenoles/química , Bifenilos Polibrominados/efectos adversos , Bifenilos Polibrominados/química , Estructura Secundaria de Proteína , Proteínas/química , Triptófano/química
7.
Int J Mol Sci ; 21(7)2020 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-32224851

RESUMEN

The aim of this study was to investigate the uptake and accumulation of fullerenol C60(OH)36 into peripheral blood mononuclear cells (PBMCs). Some additional studies were also performed: measurement of fullerenol nanoparticle size, zeta potential, and the influence of fullerenol on the ionizing radiation-induced damage to PMBCs. Fullerenol C60(OH)36 demonstrated an ability to accumulate in PBMCs. The accumulation of fullerenol in those cells did not have a significant effect on cell survival, nor on the distribution of phosphatidylserine in the plasma membrane. However, fullerenol-induced depolarization of the mitochondrial membrane proportional to the compound level in the medium was observed. Results also indicated that increased fullerenol level in the medium was associated with its enhanced transport into cells, corresponding to its influence on the mitochondrial membrane. The obtained results clearly showed the ability of C60(OH)36 to enter cells and its effect on PBMC mitochondrial membrane potential. However, we did not observe radioprotective properties of fullerenol under the conditions used in our study.


Asunto(s)
Fulerenos/farmacología , Monocitos/metabolismo , Nanopartículas/metabolismo , Transporte Biológico , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Fulerenos/química , Humanos , Potencial de la Membrana Mitocondrial , Monocitos/efectos de los fármacos , Monocitos/efectos de la radiación , Nanopartículas/química , Radiación Ionizante
8.
Chemosphere ; 227: 93-99, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30986606

RESUMEN

Currently, more and more concerns are related to oxidative stress appearing in cells as a result of xenobiotics action. It has been found that selected brominated flame retardants (BFRs) can cause reactive oxygen species (ROS) induction at environmental concentrations. Excessive ROS induction can contribute to the redox imbalance in the cell. Therefore, the aim of our work was to evaluate the effect of selected BFRs on the activity of antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the level of reduced glutathione (GSH) in human erythrocytes. Erythrocytes were incubated with tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) in the concentration ranging from 1 to 100 µg/ml. This study has shown that the BFRs studied disturbed redox balance in human erythrocytes. TBBPA caused more significant decrease in antioxidant enzymes activities than other compounds examined. Among bromophenols studied, 2,4-DBP most strongly affected antioxidant system, which indicated that the number of bromine atoms in the molecule did not significantly affect the pro-oxidative properties of the BFRs examined.


Asunto(s)
Antioxidantes/metabolismo , Retardadores de Llama/toxicidad , Bromo , Catalasa/metabolismo , Eritrocitos/efectos de los fármacos , Retardadores de Llama/análisis , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Halogenación , Humanos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Fenoles , Bifenilos Polibrominados/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
9.
Exp Mol Pathol ; 105(1): 98-109, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29909157

RESUMEN

Since the first identification of fullerenes (C60) and their synthesis in 1985, those compounds have been extensively studied in the biomedical field. In particular, their water-soluble derivatives, fullerenols (C60(OH)n, n = 2-48), have recently been the subject of numerous investigations concerning their antioxidant and prooxidant properties in biological systems. A small fraction of that research has focused on the possible use of C60 and C60(OH)n in neuroscience and the therapy of pathologies such as dementia, amyloid-ß (Aß) formation, and Parkinson's disease. However, only a few studies have focused on their direct effects on neuronal network viability and excitability, especially with the use of electrophysiological and electrochemical approaches. Therefore, we addressed the issue of the direct effect of hydroxylated fullerene nanoparticles C60(OH)36 on local field potentials at the hippocampal formation (HPC) level. With the use of in vitro hippocampal formation slices as a stable model of inducing theta oscillations, and an in vivo model of an anesthetized rat, herein we provide the first convergent electropharmacological evidence that C60(OH)36 at relatively high concentrations (60 µM and 80 µM in vitro; 0.2 µg/µl in vivo) is capable of attenuating the amplitude, power, and frequency of theta oscillations in the HPC neuronal network. At the same time, lower concentrations did not induce any apparent changes. Theta band oscillations constitute a key physiological phenotypic property, which served here as a sensitive assay enabling the study of neural network excitability. Moreover, we report that C60(OH)36 at the concentrations of 60 µM and 80 µM is capable of producing epilepsy in the HPC in vitro, which suggests that C60(OH)n, when applied at higher doses, may have a deleterious effect on the functioning of neuronal networks.


Asunto(s)
Epilepsia/etiología , Fulerenos/farmacología , Hipocampo/efectos de los fármacos , Ritmo Teta , Animales , Relación Dosis-Respuesta a Droga , Fulerenos/administración & dosificación , Fulerenos/toxicidad , Hipocampo/fisiología , Masculino , Ratas , Ratas Wistar
10.
Biochim Biophys Acta Biomembr ; 1860(8): 1528-1536, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29778781

RESUMEN

Fullerenols (polyhydroxylated fullerene C60) are nanomaterial with potentially broad applicability in biomedical sciences with high antioxidant ability, thus, we investigated the radioprotecting potential of fullerenol C60(OH)36 on human erythrocytes irradiated by high-energy electrons of 6 MeV. The results demonstrate that C60(OH)36 at concentration of 150 µg/mL protects the erythrocytes against the radiation-induced hemolysis (comparing to non-protected cells, we observed 30% and 39% protection for 0.65 and 1.3 kGy irradiation doses, respectively). The protecting effect was confirmed by 32% decreased release of potassium cations comparing to the cells irradiated without C60(OH)36. Measurements of the amount of lactate dehydrogenase (LDH) released from the irradiated erythrocytes showed that the size of the pores formed by irradiation was not sufficient to release LDH across the erythrocyte membranes. We also report a significant decrease of the affinity of acetylcholinesterase (AChE) for the substrate in the presence of fullerenol, indicating the relatively strong adsorption of C60(OH)36 to components of plasma membrane. Changes in membrane fluidity detected by fluorescence spectroscopy and conformational changes in membrane proteins detected by spin labeling suggest the dose-dependent formation of disulfide groups as an effect of oxidation and this process was inhibited by C60(OH)36. We suppose that scavenging the ROS as well as adsorption of fullerenol to membrane proteins and steric protection of -SH groups against oxidation are responsible for the observed effects.


Asunto(s)
Membrana Eritrocítica/metabolismo , Fulerenos/metabolismo , Hemólisis/efectos de los fármacos , Sustancias Protectoras/farmacología , Radiación Ionizante , Acetilcolinesterasa/metabolismo , Células Cultivadas , Electrones , Membrana Eritrocítica/química , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Fulerenos/química , Fulerenos/farmacología , Hemólisis/efectos de la radiación , Humanos , L-Lactato Deshidrogenasa/metabolismo , Fluidez de la Membrana/efectos de los fármacos , Fluidez de la Membrana/efectos de la radiación , Potasio/metabolismo , Sustancias Protectoras/síntesis química , Sustancias Protectoras/metabolismo
12.
Med Pr ; 67(6): 817-831, 2016 Dec 22.
Artículo en Polaco | MEDLINE | ID: mdl-28005089

RESUMEN

Malignant tumors are one of the main causes of death in Poland. One of the objectives of contemporary biomedical research is to maximize the effects of therapeutic strategies. The actions undertaken to improve therapeutic agents are aimed at reducing the side effects of cancer treatments. Another direction of investigations is the search for protective substances that reduce the toxicity of the drug to normal cells. Carbon-based nanomaterials (fullerenes and their derivatives, graphene, carbon nanotubes, nanodiamonds) are a broad class of nanoparticles that have potential biomedical applications in both therapy and diagnostics. The aim of this paper is to review biological properties of fullerenols in the context of their use in various strategies of cancer treatments. The authors also discuss the possibility of simultaneous use of nanoparticles in therapy and diagnosis, that is, in theranostics. Current knowledge indicates that fullerenes and their hydrophilic derivatives, especially fullerenols, show low or no toxicity. They may contribute to the inhibition of tumor growth and protection of normal cells through their antioxidant properties, as well as to the regulation of expression of genes involved in apoptosis and angiogenesis, and stimulation of the immune response. Gadoliniumcontaining endohedral fullerenes are less toxic as a contrast agents in magnetic resonance imaging, and they may also inhibit tumor growth, which is a promising result for theranostics. Med Pr 2016;67(6):817-831.


Asunto(s)
Antineoplásicos/uso terapéutico , Fulerenos/uso terapéutico , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Humanos , Polonia
13.
Biomed Res Int ; 2013: 751913, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24222914

RESUMEN

Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today's science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper.


Asunto(s)
Fulerenos/uso terapéutico , Nanomedicina , Neoplasias/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Portadores de Fármacos , Humanos , Neoplasias/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico , Estrés Oxidativo/efectos de los fármacos , Agua/química
14.
Postepy Hig Med Dosw (Online) ; 67: 859-72, 2013 Aug 23.
Artículo en Polaco | MEDLINE | ID: mdl-24018451

RESUMEN

Fullerenols, the water-soluble derivatives of fullerenes, are currently being recently intensively studied in the context of the possibility of their application in the biomedicine. Due to their hydrophilic properties and the ability to eliminate free radicals, fullerenols may in the future provide a solid alternative to currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases and radiobiology. Depending on the research protocol applied, fullerenols may also act as pro oxidants. The dualistic nature of fullerenols may contribute to finding new biomedical applications of these agents in the future, by exerting a cytotoxic or protective effect respectively against cancer cells or healthy cells. Because of the encapsulated structure of fullerenols, there exists the possibility of their application in medical diagnostics in the transfer of contrast agents or in the drug transport. During the planning of an experiment designed to investigate the effects of radiation in combination with derivatives of water-soluble fullerenes, the possibility of appearance of the "dose-response effect" should be taken into consideration since it significantly contributes to one of the two possible effects: protection or sensitization. The same applies to the possibility of using these compounds as potential neuroprotectors. Fullerenol may protect neurons in the particular areas of the brain but in the definedcertain doses it may also induce cell death. A giant leap in the field of nanotechnology not only leads scientists to search for new applications of nanomaterials such as fullerenols, but also raises the question about their harmful effect on the environment. High utilization of hardly biodegradable fullerenols increases the likelihood of their accidental release into natural systems and their bioaccumulation. Despite convincing evidences about the potential applications of fullerenols in biomedicine, we still have insufficient knowledge about the mechanism of action of these molecules and their possible side effects.


Asunto(s)
Fulerenos/química , Fulerenos/farmacología , Sustancias Protectoras/farmacología , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Nanoestructuras , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Sustancias Protectoras/química
15.
Biochim Biophys Acta ; 1828(9): 2007-14, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23702461

RESUMEN

The present study was aimed at investigating the effect of fullerenol C60(OH)36 on chosen parameters of the human erythrocyte membrane and the preliminary estimation of the properties of fullerenol as a potential linking agent transferring the compounds (e.g., anticancer drugs) into the membrane of erythrocytes. The results obtained in this study confirm the impact of fullerenol on erythrocyte cytoskeletal transmembrane proteins, particularly on the band 3 protein. The presence of fullerenol in each of the concentrations used prevented degradation of the band 3 protein. The results show that changes in the morphology of red blood cells caused by high concentrations of fullerenol (up to 150mg/L) did not lead to increased red blood cell hemolysis or the leakage of potassium. Moreover, fullerenol slightly prevented hemolysis and potassium efflux. The protective effect of fullerenol at the concentration of 150mg/L was 20.3%, and similar results were obtained for the efflux of potassium. The study shows that fullerenol slightly changed the morphology of the cells and, therefore, altered the intracellular organization of erythrocytes through the association with cytoskeletal proteins.


Asunto(s)
Proteína 1 de Intercambio de Anión de Eritrocito/química , Citoesqueleto/efectos de los fármacos , Portadores de Fármacos/química , Membrana Eritrocítica/efectos de los fármacos , Fulerenos/química , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Forma de la Célula/efectos de los fármacos , Células Cultivadas , Citoesqueleto/química , Citoesqueleto/metabolismo , Portadores de Fármacos/farmacología , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Fulerenos/farmacología , Hemólisis/efectos de los fármacos , Humanos , Potasio/metabolismo , Unión Proteica
16.
Int J Biol Macromol ; 57: 38-44, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23474396

RESUMEN

The aim of this work was to examine the effect of two organophosphorous compounds i.e. bromfenvinphos (BFVF) and chlorfenvinphos (CFVF) possessing acaricidal and insecticidal properties, on the activity of human erythrocytes acetylcholinesterase (AChE, EC 3.1.1.7). Moreover, the effect of five bromfenvinphos production impurities on AChE activity was studied. The erythrocytes were incubated with the compounds studied in the concentrations range from 0.05 to 250 µM for 1h. The organophosphorous compounds studied in low concentrations increased Km value but they did not change Vmax value (competitive inhibition). Higher concentrations of the compounds studied decreased Vmax value and increased Km value, what revealed a mixed type of AChE inhibition by these xenobiotics. Basic significance in AChE activity inhibition has the type of halogen in vinyl group. Chlorfenvinphos (insecticide) exhibited stronger enzyme inhibition than bromfenvinphos. CFVF and dibromo-bromfenvinphos possessed the lowest Ki and Ki' values among all the compounds studied. The presence of Cl atom (chlorfenvinphos) instead of Br atom (bromfenvinphos) considerably increases antiesterase activity of the individual compound. Three impurities like 2,4-dichlorophenacyl bromide, 2,4-dichlorophenacylidene bromide and 2,4-dichlorophenacylidyne bromide did not induce any statistically changes in AChE activity. Two impurities of bromfenvinphos such as: dihydro-bromfenvinphos and dibromo-bromfenvinphos revealed significant effect on the AChE activity, which may be connected with the presence a phosphate group in these substances. It was proven that an increase in antiesterase activitiy of the compounds studied corresponded with the increase in the number of Br atoms at carbon of their vinyl group: dibromo-bromfenvinphos>bromfenvinphos>dihydro-bromfenvinphos.


Asunto(s)
Acetilcolinesterasa/química , Clorfenvinfos/análogos & derivados , Clorfenvinfos/química , Inhibidores de la Colinesterasa/química , Eritrocitos/enzimología , Contaminación de Medicamentos , Humanos
17.
Biochim Biophys Acta ; 1828(2): 241-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22989725

RESUMEN

The influence of fullerenol on the activities of human erythrocyte membrane ATPases and the fluidity of the plasma membrane as well as the possibility of fullerenol incorporation into the plasma membrane were investigated. Fullerenol at concentrations up to 150 µg/mL induced statistically significant decreases in the anisotropy of 1-anilino-8-naphthalene sulfonate (ANS) (14%), N,N,N-trimethyl-4-(6-phenyl-1,3,5,-hexatrien-1-yl)phenylammonium p-toluenesulfonate (TMA-DPH) (7.5%) and 1,6-diphenyl-1,3,5-hexatriene (DPH) (9.5%) after a 1-hour incubation at 37°C. The effect disappeared for ANS and TMA-DPH, but not for DPH, after washing out the fullerenol. Incubation of erythrocyte membranes with fullerenol led to decreases in the activities of Na(+),K(+)-ATPase (to 23% of the control value), Ca(2+)-ATPase (to 16% of control) and Mg(2+)-ATPase (to 22% of control). Washing out the fullerenol lessened the inhibition of the Na(+),K(+)-ATPase (37% of control) and Ca(2+)-ATPase (23.5% of control); however, it did not influence Mg(2+)-ATPase activity. Furthermore, fullerenol could associate with erythrocyte plasma membranes. Our results suggest that fullerenol associates primarily with the surface of the plasma membrane; however, it can also migrate deeper inside the membrane. Moreover, fullerenol influences membrane ATPases so that it may modulate ion transport across membranes.


Asunto(s)
Adenosina Trifosfatasas/química , Membrana Eritrocítica/metabolismo , Eritrocitos/enzimología , Fulerenos/química , Anisotropía , Transporte Biológico , ATPasa de Ca(2+) y Mg(2+)/química , ATPasas Transportadoras de Calcio/química , Membrana Celular/metabolismo , Relación Dosis-Respuesta a Droga , Eritrocitos/citología , Humanos , Iones , Fluidez de la Membrana , ATPasa Intercambiadora de Sodio-Potasio/química , Propiedades de Superficie
18.
Postepy Biochem ; 56(4): 456-62, 2010.
Artículo en Polaco | MEDLINE | ID: mdl-21473050

RESUMEN

Molecule of fullerene, having a spherical or ellipsoidal shape, is made of rings consisting of five or six carbon atoms, combined with conjugated pi bonds. Delocalization of pi electrons in the molecule of fullerene makes it easy to scavenge free radicals. But, despite being the effective antioxidants and radical scavengers fullerenes may be prooxidants by reactive oxygen species generation. Mammalian cells consist mainly of water (about 70%). Thus, the radical and non-radical products of water radiolysis are the basic sources of radiation damage to biomolecules. Reactive oxygen species, such as hydroxyl (HO*) and superoxide (O2-*) radicals and hydrogen peroxide (H2O2), are responsible for radiation-induced damage in aerated systems. Free radical mechanism of radiation damage suggests that scavengers of free radicals should protect cellular structures against damage. Electron donor compounds should also exhibit protective properties towards oxidized functional groups by reducing them. However, the electron transfer from fullerene to oxygen may generate superoxide radical. The shape of fullerenes allows them to act as carriers of radioactive atoms of isotopes used in the therapy and medical diagnostics. Fullerenes and their derivatives due to its properties are new promising chemicals for application in radiobiology. Fullerenes may be radioprotectors, radiosensitizer or auxiliary compounds in diagnostic imaging. What they are depends on the experimental system used.


Asunto(s)
Fulerenos/química , Fulerenos/farmacología , Protectores contra Radiación/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Animales , Radicales Libres/metabolismo , Humanos , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/prevención & control , Protectores contra Radiación/química , Fármacos Sensibilizantes a Radiaciones/química , Radiobiología/métodos
19.
Food Chem Toxicol ; 46(1): 359-67, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17889420

RESUMEN

Although it is known that phenoxyacetic herbicides significantly affect the oxidative status of human erythrocytes, there is no direct evidence of their ability to induce free radical production. To demonstrate this phenomenon we investigated the effect of two commonly used phenoxyherbicides-sodium salt of 2,4-dichlorophenoxyacetic acid (2,4-D-Na) and sodium salt of 4-chloro-2-methylphenoxyacetic acid (MCPA-Na) on oxidation of dihydrorhodamine 123 and H(2)DCFDA as well as on carbonyl group content in cellular proteins. Moreover, haemoglobin denaturation was also measured. The rate of fluorescent probe oxidation was significantly higher for 2,4-D-Na, while both compounds exerted similar effects on protein carbonyl group (an increase in their content) and on denaturation of haemoglobin (no changes were observed). These results and the previous data led us to a conclusion that pro-oxidative action of phenoxyherbicides is strongly dependent on the localization of the substituent in the phenol ring. We also proposed a metabolic reaction chain that explains the mechanism of action of 2,4-D-Na in vivo.


Asunto(s)
Ácido 2,4-Diclorofenoxiacético/toxicidad , Ácido 2-Metil-4-clorofenoxiacético/toxicidad , Eritrocitos/metabolismo , Radicales Libres/sangre , Herbicidas/toxicidad , Rodaminas/metabolismo , Eritrocitos/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Humanos , Técnicas In Vitro , Indicadores y Reactivos , Cinética , Oxidación-Reducción , Carbonilación Proteica/efectos de los fármacos , Desnaturalización Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
20.
Postepy Biochem ; 53(1): 91-6, 2007.
Artículo en Polaco | MEDLINE | ID: mdl-17718393

RESUMEN

Fullerenes are chemical structures made of carbon atoms. The stable form is molecule composed of 60 carbon atoms arranged in a soccer ball-shaped structure. With respect to its electron donor and acceptor capability and photochemical behavior fullerenes can be effective antioxidants and radical scavengers or prooxidants and photosensitizers. These properties of fullerenes have paid attention on their possible biological applications. Results of previous studies point to the great dependance of fullerenes activity upon quality, quantity and geometry of substituents in fullerene derivatives. Some of fullerene derivatives show antiviral and antimicrobial activity, including anti-HIV properties. C60 and its derivatives are able to exhibit cytotoxic and enzyme-inhibiting abilities as well as radical-quenching and antioxidative abilities. Generation of reactive oxygen species under influence of visible light is another ability of fullerene derivetives desired in photodynamic therapy.


Asunto(s)
Carbono/química , Carbono/farmacología , Fulerenos/química , Fulerenos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Antivirales/química , Antivirales/farmacología , Oxidantes/química , Oxidantes/farmacología , Oxidación-Reducción , Fotoquímica/métodos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores
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