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1.
Dokl Biochem Biophys ; 486(1): 238-242, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367830

RESUMO

The results of the study of the effect of a mononuclear dinitrosyl iron complex (DNIC7) with functional sulfur-containing ligands (NO donors) on the viability of multiple myeloma cells are presented. It was shown that DNIC7 decreased cell viability and inhibited the proliferation of multiple myeloma cells, i.e., exhibits cytotoxic properties. Fluorescent analysis showed that the DNIC7 compound decreases the level of intracellular glutathione and increases the level of reactive oxygen species in multiple myeloma cells. It is assumed that DNIC7 has a therapeutic potential for the treatment of cancer.


Assuntos
Antineoplásicos/farmacologia , Ferro/farmacologia , Mieloma Múltiplo/patologia , Óxidos de Nitrogênio/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo
2.
Bioresour Technol ; 289: 121688, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31247529

RESUMO

This study investigated the effects of adding nano-zerovalent iron (nZVI) at three concentrations (0, 80, and 160 mg/L) on the methane yield and the fate of antibiotic resistance genes (ARGs) during the anaerobic digestion (AD) of cattle manure. The addition of nZVI effectively enhanced the methane yield, where it significantly increased by 6.56% with 80 mg/L nZVI and by 6.43% with 160 mg/L nZVI. The reductions in the abundances of ARGs and Tn916/1545 were accelerated by adding 160 mg/L nZVI after AD. Microbial community analysis showed that nZVI mainly increased the abundances of bacteria with roles in hydrolysis and acidogenesis, whereas it reduced the abundance of Acinetobacter. Redundancy analysis indicated that the changes in mobile genetic elements made the greatest contribution to the fate of ARGs. The results suggest that 160 mg/L nZVI is a suitable additive for reducing the risks due to ARGs in AD.


Assuntos
Resistência Microbiana a Medicamentos , Ferro/farmacologia , Esterco/microbiologia , Anaerobiose , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Bovinos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Metano/biossíntese
3.
Chemosphere ; 226: 413-420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951935

RESUMO

Cd has high activity and bioavailability and is a poisonous element to plants. As a critical ecosysterm, mangroves are subjected to serious Cd pollution. In this research, the hypothesis was presented that improving Fe bioavailability would alleviate Cd phytotoxicity to Avicennia marina (Forsk.) Vierh. To test this, we examined the effect of four exogenous Fe and three Cd concentrations on A. marina. The results showed that a significant positive correlation excited between moderate exogenous Fe concentration and Cd tolerance of A. marina. Moderate exogenous Fe concentration directly or indirectly promoted the formation of Fe plaque, which immobilised more Cd on the root surface and decreased Cd absorption in roots. Furthermore, an exogenous Fe application increased plant biomass and Fe accumulation in A. marina tissues. This improved the competition between Fe and Cd within the plants. Therefore, an Fe application facilitated a decrease in Cd toxicity within A. marina. Simultaneously, a moderate Fe concentration caused an increase in low-molecular-weight organic acid (LMWOA) secretion from the roots. Meanwhile, Cd can be chelated/complexed by LMWOAs. It also played a crucial role in Cd detoxification in A. marina. In conclusion, Fe application accelerated the growth and enhanced Cd tolerance of A. marina. Therefore, improving Fe bioavailability will protect mangroves from Cd contamination.


Assuntos
Avicennia/efeitos dos fármacos , Cádmio/toxicidade , Ferro/uso terapêutico , Raízes de Plantas/efeitos dos fármacos , Avicennia/química , Ferro/farmacologia , Raízes de Plantas/química
4.
Chemosphere ; 226: 431-438, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951937

RESUMO

Arsenic (As) contamination of drinking water is a major cause of As toxicity in many parts of the world. A study was conducted to evaluate As removal from water containing 100-700 µg/L of As and As to Fe concentration ratios of 1:5-1:1000 using the coprecipitation process with and without As/Fe adsorption onto granular activated carbon (GAC). Fe concentration required to reduce As concentrations in order to achieve the WHO standard level of 10 µg/L increased exponentially with the increase in initial As concentration. When small amounts of GAC were added to the As/Fe solutions the Fe required to remove these As concentrations reduced drastically. This decline was due to the GAC adsorption of Fe and As, enhancing the removal of these metals through coprecipitation. Predictive regression equations were developed relating the GAC dose requirement to the initial As and Fe concentrations. Zeta potential data revealed that As was adsorbed on the GAC by outer-sphere complexation whereas Fe was adsorbed by inner-sphere complexation reversing the negative charge on GAC to positive values. X-ray diffraction of the GAC samples in the presence of Fe had an additional peak characteristic of ferrihydrite (Fe oxide) compared to that of the GAC sample without Fe. The study showed that incorporating an adsorbent into the coprecipitation process has the advantage of removing As from waters at all concentrations of Fe and As compared to coprecipitation alone which does not remove As to the required levels if Fe concentration is low.


Assuntos
Arsênico/efeitos adversos , Ferro/uso terapêutico , Poluentes Químicos da Água/química , Adsorção , Ferro/farmacologia
5.
Mater Sci Eng C Mater Biol Appl ; 98: 930-938, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813100

RESUMO

Hyperthermia-increasing temperature of cancerous tissue for a short period of time-is considered as an effective treatment for various cancer types such as malignant bone tumors. Superparamagnetic and ferromagnetic particles have been studied for their hyperthermic properties in treating various types of cancers. The activation of magnetic nanoparticles by an alternating magnetic field is currently being explored as a technique for targeted therapeutic heating of different tumors and is being studied as an adjuvant to conventional chemotherapy and radiation therapy. In the case of bone cancers, to increase the efficiency of treatment in the hyperthermia therapy, employed materials should support bone regeneration as well. Magnetite is one of the most attractive magnetic nanoceramics used in hyperthermia application. However, biocompatibility and bioactivity of this material have raised questions. There is a high demand for extremely efficient hyperthermia materials which are equally biocompatible to non-tumor cells and tissues. We report the development of a biocompatible and bioactive material with desirable magnetic properties that show excellent hyperthermia properties and can be used for destruction of the cancerous tissue in addition to supporting tissue regeneration for treatment of bone tumors. In the current study, iron (Fe3+)-containing HT nanostructured material was prepared, and its biocompatibility, bioactivity, and hyperthermia abilities were studied. The developed materials showed effective hyperthermic properties with increased biocompatibility as compared to magnetite.


Assuntos
Neoplasias Ósseas/terapia , Hipertermia Induzida , Ferro/farmacologia , Magnetismo , Nanopartículas de Magnetita/química , Silicatos/farmacologia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Difusão Dinâmica da Luz , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pós , Difração de Raios X
6.
Mater Sci Eng C Mater Biol Appl ; 99: 552-562, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889729

RESUMO

In this work, two new α +â€¯ß titanium alloys with low contents of ubiquitous and low-cost alloying elements (i.e., Mo and Fe) were designed on the basis of the electronic parameters and molybdenum equivalent approaches. The designed Ti - 2Mo - 0.5Fe at. % (TMF6) and Ti - 3Mo - 0.5Fe at. % (TMF8) alloys were produced using arc melting process for studying their mechanical, electrochemical and cytotoxicity compatibilities and comparing these compatibilities to those of Ti-6Al-4V ELI alloy. The cost of the used raw materials for producing the TMF6 and TMF8 alloys are almost 1/6 of those for producing the Ti-6Al-4V ELI alloy. The hardness of the two alloys are higher than that of the Ti-6Al-4V ELI alloy, while their Young's moduli (in the range of 85-82 GPa) are lower than that of the Ti-6Al-4V ELI alloy (110 GPa). Increasing the Mo equivalent from 6 (in TMF6 alloy) to 8 (in TMF8 alloy) led to an increase in the plastic strain percent from 4% to 17%, respectively, and a decrease in the ultimate tensile strength from 949 MPa to 800 MPa, respectively. The microstructure of TMF6 alloy consists of α'/α″ phases, while TMF8 alloy substantially consists of α″ phase. The corrosion current densities and the film resistances of the new alloys are in the range of 0.70-1.07 nA/cm2 and on the order of 105â€¯Ω·cm2, respectively. These values are more compatible with biomedical applications than those measured for the Ti-6Al-4V ELI alloy. Furthermore, the cell viabilities of the TMF6 and TMF8 alloys indicate their improved compatibility compared to that of the Ti-6Al-4V ELI alloy. The CCK-8 (Cell Counting Kit-8) assay was conducted to investigate the cytotoxicity, proliferation, and shape index of the cells of the candidate alloys. Overall, the measured compatibility of the new V-free low-cost alloys, particularly TMF8, makes them promising candidates for replacing the Ti-6Al-4V ELI alloy in biomedical applications.


Assuntos
Ligas/farmacologia , Materiais Biocompatíveis/economia , Materiais Biocompatíveis/farmacologia , Custos e Análise de Custo , Ferro/farmacologia , Molibdênio/farmacologia , Implantação de Prótese , Titânio/farmacologia , Ligas/economia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Forma Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corrosão , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Espectroscopia Dielétrica , Módulo de Elasticidade , Técnicas Eletroquímicas , Dureza , Camundongos , Estresse Mecânico , Resistência à Tração , Difração de Raios X
7.
Met Ions Life Sci ; 192019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30855107

RESUMO

Intravenous (IV) iron is widely used to provide supplementation when oral iron is ineffective or not tolerated. All commercially available intravenous iron formulations are comprised of iron oxyhydroxide cores coated with carbohydrates of varying structure and branch characteristics. The diameter of the iron-carbohydrate complexes ranges from 5-100 nm and meets criteria for nanoparticles. Clinical use of IV iron formulations entered clinical practice beginning of the late 1950s, which preceded the nanomedicine exploration frontier. Thus, these agents were approved without full exploration of labile iron release profiles or comprehensive biodistribution studies. The hypothesis for the pathogenesis of acute oxidative stress induced by intravenous iron formulations is the release of iron from the iron-carbohydrate structure, resulting in transient concentrations of labile plasma iron and induction of the Fenton chemistry and the Haber-Weiss reaction promoting formation of highly reactive free radicals such as the hydroxyl radical. Among available IV iron formulations, products with smaller carbohydrate shells are more labile and more likely to release labile iron directly into the plasma (i.e., before metabolism by the reticuloendothelial system). The proposed biologic targets of labile-iron-induced oxidative stress include nearly all systemic cellular components including endothelial cells, myocardium, liver as well as low density lipoprotein and other plasma proteins. Most studies have relied on plasma pharmacokinetic analyses that require many model assumptions to estimate contribution of the iron-carbohydrate complex to elevations in serum iron indices and hemoglobin. Additionally, the commercially available formulations have not been well studied with regard to optimal dosing regimens, long-term safety and comparative efficacy. The IV iron formulations fall into a class defined by the Food and Drug Administration as "Complex Drugs" and thus present considerable challenges for bioequivalence evaluation.


Assuntos
Compostos Férricos/farmacologia , Ferro/farmacologia , Nanopartículas Metálicas , Composição de Medicamentos , Humanos , Ferro/administração & dosagem , Ferro/farmacocinética , Estresse Oxidativo , Distribuição Tecidual
8.
Nutrients ; 11(3)2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30875895

RESUMO

Although dietary iron is a determinant of iron status in animals, body fat mass has been reported to have an inverse association with iron status in human studies. The goal of this study was to determine the relationship between Fe homeostasis, body composition, energy expenditure and neuroendocrine regulators for severe Fe-deficiency anaemia. Forty male Wistar albino rats recently weaned were divided at random into two groups: the control group was fed the basal diet, AIN-93G diet (normal-Fe) and the anaemic group received a low-Fe diet for 40 days. Neuroendocrine parameters that regulate basal metabolism and appetite (thyroid hormones, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, adrenocorticotropic hormone and corticosterone), body composition, respiratory volumes, energy expenditure, haematological and biochemical were assessed. Total body fat was lower, whereas lean mass, free and total water were higher in the anemic group. O2 consumption, CO2 production, energy expenditure (EE) and respiratory quotient (RQ) were lower in the Fe-deficient animals. Triiodothyronine and thyroxine hormones decreased, while thyroid-stimulating hormone increased in the anemic group. Circulating levels of ghrelin were lower in the anemic group, while GIP, glucagon, insulin, corticosterone and adrenocorticotropic hormone levels were higher. Fe-deficiency impairs weight gain in the rats, with marked reductions in lean mass and body fat, indicating lower energy stores.


Assuntos
Anemia Ferropriva/metabolismo , Metabolismo Basal/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ferro , Animais , Dieta , Ferro/deficiência , Ferro/metabolismo , Ferro/farmacologia , Masculino , Ratos , Ratos Wistar
9.
Virulence ; 10(1): 234-247, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30880633

RESUMO

Aspergillus fumigatus is the most prevalent airborne fungal pathogen that causes invasive fungal infections in immunosuppressed individuals. Adaptation to iron limited conditions is crucial for A. fumigatus virulence. To identify novel genes that play roles in adaptation to low iron conditions we performed an insertional mutagenesis screen in A. fumigatus. Using this approach, we identified the tptA gene in A. fumigatus, which shares homology with the Saccharomyces cerevisiae thiamine pyrophosphate (ThPP) transporter encoding gene tpc1. Heterologous expression of tpc1 in the tptA deletion mutant completely restored the ThPP auxotrophy phenotype, suggesting that Tpc1 and TptA are functional orthologues. Importantly, TptA was required for adaptation to low iron conditions in A. fumigatus. The ΔtptA mutant had decreased resistance to the iron chelator bathophenanthroline disulfonate (BPS) with severe growth defects. Moreover, loss of tptA decreased the expression of hapX, which is a major transcription factor indispensable for adaptation to iron starvation in A. fumigatus. Overexpression of hapX in the ΔtptA strain greatly rescued the growth defect and siderophore production by A. fumigatus in iron-depleted conditions. Mutagenesis experiments demonstrated that the conserved residues related to ThPP uptake in TptA were also required for low iron adaptation. Furthermore, TptA-mediated adaptation to low iron conditions was found to be dependent on carbon sources. Finally, loss of tptA resulted in the attenuation of virulence in a murine model of aspergillosis. Taken together, this study demonstrated that the mitochondrial ThPP transporter TptA promotes low iron adaptation and virulence in A. fumigatus.


Assuntos
Aspergillus fumigatus/genética , Aspergillus fumigatus/patogenicidade , Proteínas Fúngicas/genética , Ferro/metabolismo , Proteínas Mitocondriais/metabolismo , Tiamina Pirofosfato/metabolismo , Animais , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Transporte Biológico , Regulação Fúngica da Expressão Gênica , Ferro/farmacologia , Masculino , Camundongos , Proteínas Mitocondriais/genética , Aspergilose Pulmonar/microbiologia , Saccharomyces cerevisiae/genética , Fatores de Transcrição , Virulência
10.
Bioresour Technol ; 282: 202-210, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30861450

RESUMO

Weak magnetic field (WMF) provided by a magnet was proposed to enhance CH4 production from a swine manure-fed digester supplemented with micron-sized zero valent iron (ZVI). Compared to the control without ZVI addition and WMF application (RControl), treatments that included ZVI only (RZVI) and coupled WMF with ZVI (RZVI/WMF) increased the CH4 production by 77.0% and 124.5%, respectively. As evidenced by the elevated levels of total soluble iron, WMF apparently promoted the corrosion of ZVI, providing extra H2 for hydrogenotrophic methanogenesis and creating a more reductive environment to reduce propionic-type fermentation. Microbial analysis results revealed that the relative abundance of Methanothrix (capable of accepting electrons) in RZVI/WMF were 75.1% higher than that in RZVI. Essentially, WMF application promoted the direct interspecies electron transfer-based methanogenesis by (1) providing more electrons as the direct substrate, and (2) inducing Lorentz force to facilitate the mass transfer between the released electrons and the methanogens.


Assuntos
Ferro/farmacologia , Campos Magnéticos , Metano/metabolismo , Animais , Corrosão , Fermentação/efeitos dos fármacos , Esterco , Suínos
11.
J Pediatr Endocrinol Metab ; 32(3): 275-280, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30796846

RESUMO

Background It is known that iron deficiency anemia effects appetite and growth negatively. The aim of this study was to investigate the effect of iron therapy on appetite, growth and plasma ghrelin and leptin levels in children aged between 12 and 24 months with isolated nutritional iron deficiency anemia. Methods Iron deficiency anemia was diagnosed by clinic and laboratory findings. All 19 cases were given 5 mg/kg/day iron therapy for 3 months. Results The mean plasma ghrelin level was 936.7±428.8 pg/mL before therapy and it increased to 1284.7±533.3 pg/mL (p<0.001) while the mean plasma leptin level decreased from 3.4±1.6 ng/mL to 1.9±1.0 ng/mL (p<0.01) after therapy. The amount of daily caloric intake, carbohydrate and protein intake were significantly increased after therapy (p<0.001). Δ body weight was correlated with plasma ghrelin levels before and after therapy significantly. Conclusions In conclusion, the findings of this study indicate that plasma ghrelin level increases and leptin level decreases and growth accelerates because of an increase in appetite and daily calories, carbohydrate and protein amount in children with nutritional iron deficiency anemia after iron therapy. The increase in appetite and acceleration on growth in iron deficiency anemia might result from decreased leptin and increased plasma ghrelin levels. The most important finding of this study is significantly increased plasma ghrelin levels after iron therapy, and this finding might be related to both the improved appetite and catch-up growth.


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Apetite/fisiologia , Grelina/sangue , Ferro/uso terapêutico , Leptina/sangue , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Lactente , Ferro/farmacologia , Masculino , Resultado do Tratamento
12.
Vitam Horm ; 110: 101-129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798807

RESUMO

Iron, an essential nutrient, is required for many biological processes but is also toxic in excess. The lack of a mechanism to excrete excess iron makes it crucial for the body to regulate the amount of iron absorbed from the diet. This regulation is mediated by the hepatic hormone hepcidin. Hepcidin also controls iron release from macrophages that recycle iron and from hepatocytes that store iron. Hepcidin binds to the only known iron export protein, ferroportin, inducing its internalization and degradation and thus limiting the amount of iron released into the plasma. Important regulators of hepcidin, and therefore of systemic iron homeostasis, include plasma iron concentrations, body iron stores, infection and inflammation, hypoxia and erythropoiesis, and, to a lesser extent, testosterone. Dysregulation of hepcidin production contributes to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and non-transfused ß-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic inflammatory diseases and inherited iron-refractory iron-deficiency anemia. The present review summarizes our current understanding of the molecular mechanisms and signaling pathways contributing to hepcidin regulation by these factors and highlights the issues that still need clarification.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/metabolismo , Ferro/farmacologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Regulação da Expressão Gênica/fisiologia , Hepcidinas/genética , Humanos , Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/metabolismo , Transdução de Sinais
13.
Vitam Horm ; 110: 17-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798811

RESUMO

Hepcidin is central to regulation of iron metabolism. Its effect on a cellular level involves binding ferroportin, the main iron export protein, resulting in its internalization and degradation and leading to iron sequestration within ferroportin-expressing cells. Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron restricted erythropoiesis. Furthermore, insufficiently elevated hepcidin occurs in multiple diseases associated with iron overload. Abnormal iron metabolism as a consequence of hepcidin dysregulation is an underlying factor resulting in pathophysiology of multiple diseases and several agents aimed at manipulating this pathway have been designed, with some already in clinical trials. In this chapter, we present an overview of and rationale for exploring the development of hepcidin agonists and antagonists in various clinical scenarios.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Hepcidinas/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Ferro/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/genética , Humanos , Ferro/farmacologia , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/terapia , Transdução de Sinais
14.
J Neuroinflammation ; 16(1): 41, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777083

RESUMO

BACKGROUND: Excessive iron contributes to oxidative stress after central nervous system injury. NADPH oxidase (NOX) enzymes are upregulated in microglia after pro-inflammatory activation and contribute to oxidative stress. The relationship between iron, microglia, NOX, and oxidative stress is currently unclear. METHODS: We evaluated the effects of iron on lipopolysaccharide (LPS)-activated microglia and its secondary effect within neuronal co-cultures. Further, NOX2 and four specific inhibitors were tested to evaluate the relationship with the reactive oxygen species (ROS)-producing enzymes. RESULTS: An iron dose-dependent increase in ROS production among microglia treated with LPS was identified. Interestingly, despite this increase in ROS, inflammatory polarization alterations were not detected among the microglia after exposure to iron and LPS. Co-culture experimentation between primary neurons and exposed microglia (iron and LPS) significantly reduced neuronal cell number at 24 h, suggesting a profound neurotoxic effect despite the lack of a change in polarization phenotype. NOX2 and NOX4 inhibition significantly reduced ROS production among microglia exposed to iron and LPS and reduced neuronal damage and death in response to microglial co-culture. CONCLUSIONS: In conclusion, iron significantly increased ROS production and neurotoxicity without exacerbating LP-activated microglia phenotype in vitro, suggesting that iron contributes to microglia-related oxidative stress, and this may be a viable therapeutic target for injury or neurodegeneration. Further, this study highlights both NOX2 and NOX4 as potential therapeutic targets in the treatment of iron-induced microglia-related inflammation and neurotoxicity.


Assuntos
Ferro/farmacologia , Microglia/efeitos dos fármacos , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Aminopiridinas/farmacologia , Animais , Animais Recém-Nascidos , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Cocultura , Inibidores Enzimáticos/farmacologia , Ferritinas/genética , Ferritinas/metabolismo , Ferro/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/fisiologia , Neurônios/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pirazóis/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia
15.
Biomater Sci ; 7(4): 1311-1322, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30734774

RESUMO

Addressing nanomedicine resistance is critical for its ultimate clinical success; despite this, advancing the therapeutic designs for cancer therapy are rarely discussed in the literature. In this study, we discovered that ferroptosis is the central mechanism governing the therapeutic efficacy and resistance of treatment with zero-valent iron nanoparticles (ZVI NPs). In ZVI-sensitive oral cancer cells, ZVI NPs-induced ferroptosis was characterized by mitochondrial lipid peroxidation and reduced levels of glutathione peroxidases (GPx) in subcellular organelles. However, resistant cells could attenuate ZVI-induced oxidative stress and GPx reduction. They also showed stronger mitochondrial respiration ability, thus resisting ZVI NPs-induced mitochondrial membrane potential loss. Transcriptome comparison and quantitative polymerase chain reaction (qPCR) analysis revealed that ZVI-resistant cancer cells expressed a gene set related to enhanced NADPH supply, higher detoxification capacity of reactive oxygen species, and decreased sensitivity to ferroptosis inducers (FINs). Finally, we discovered that certain FINs were able to sensitize ZVI-resistant cancer cells to become treatable without compromising healthy non-malignant cells. These findings suggest that ferroptosis can serve as a druggable target for anti-cancer nanomedicine and therapeutic resistance modulation using ZVI NPs.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ferro/farmacologia , Neoplasias Bucais/tratamento farmacológico , Nanopartículas/química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ferro/química , Neoplasias Bucais/patologia , Relação Estrutura-Atividade
16.
Iran Biomed J ; 23(3): 209-19, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30797225

RESUMO

Background: Magnetotactic bacteria are a heterogeneous group of Gram-negative prokaryote cells that produce linear chains of magnetic particles called magnetosomes, intracellular organelles composed of magnetic iron particles. Many important applications have been defined for magnetic nanoparticles in biotechnology, such as cell separation applications, as well as acting as carriers of enzymes, antibodies, or anti-cancer drugs. Since the bacterial growth is difficult and the yield of magnetosome production is low, the application of magnetosome has not been developed on a commercial scale. Methods: Magnetospirillum gryphiswaldense strain MSR-1 was used in a modified current culture medium supplemented by different concentrations of oxygen, iron, carbon, and nitrogen, to increase the yield of magnetosomes. Results: Our improved MSR-1 culture medium increased magnetosome yield, magnetosome number per bacterial cell, magnetic response, and bacterial cell growth yield significantly. The yield of magnetosome increased approximately four times. The optimized culture medium containing 25 mM of Na-pyruvate, 40 mM of NaNO3, 200 µM of ferrous sulfate, and 5-10 ppm of dissolved oxygen (DO) resulted in 186.67 mg of magnetosome per liter of culture medium. The iron uptake increased significantly, and the magnetic response of the bacteria to the magnetic field was higher than threefold as compared to the previously reported procedures. Conclusion: This technique not only decreases the cultivation time but also reduces the production cost. In this modified method, the iron and DO are the major factors affecting the production of magnetosome by M. gryphiswaldense strain MSR-1. However, refining this technique will enable a further yield of magnetosome and cell density.


Assuntos
Meio Ambiente , Magnetossomos/metabolismo , Magnetospirillum/metabolismo , Carbono/farmacologia , Ferro/farmacologia , Magnetossomos/efeitos dos fármacos , Magnetossomos/ultraestrutura , Magnetospirillum/efeitos dos fármacos , Magnetospirillum/crescimento & desenvolvimento , Magnetospirillum/ultraestrutura , Nitrogênio/farmacologia , Oxigênio/farmacologia , Ácido Pirúvico/farmacologia
17.
J Basic Microbiol ; 59(4): 385-391, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30706958

RESUMO

The effects of varying concentrations (ranging from 0 to 10 µM) of two different metals that is, iron (Fe) and copper (Cu) on indigenous bacterial populations and their hydrolytic enzyme activities within the bacterioplankton assemblages from the surface waters of the Kalamazoo River were examined under controlled microcosm conditions. The two metals were added to water samples collected from the Kalamazoo River and examined for bacterial abundance and leucine aminopeptidase activities at various time intervals over a 48 h incubation period in the dark. Results revealed no concentration effects on the bacterial populations in the presence of both Fe and Cu, although the bacterial numbers varied significantly over time in both microcosms. Conversely, leucine aminopeptidase activities based on post-hoc tests using Bonferroni correction revealed significant differences to increasing concentrations of both metals over the study period. These results further validate previous knowledge regarding the importance of various metal ions in regulating bacterial community structures and also suggest that aminopeptidase have the potential of effectively functioning using diverse trace and heavy metals as extracellular peptidase cofactors in aquatic systems.


Assuntos
Bactérias/efeitos dos fármacos , Metais Pesados/farmacologia , Fitoplâncton/efeitos dos fármacos , Rios/microbiologia , Microbiologia da Água , Poluentes Químicos da Água/farmacologia , Bactérias/enzimologia , Bactérias/crescimento & desenvolvimento , Proteínas de Bactérias/análise , Cobre/metabolismo , Cobre/farmacologia , Ferro/metabolismo , Ferro/farmacologia , Leucil Aminopeptidase/análise , Metais Pesados/metabolismo , Michigan , Fitoplâncton/enzimologia , Fitoplâncton/crescimento & desenvolvimento , Rios/química , Poluentes Químicos da Água/metabolismo
18.
J Basic Microbiol ; 59(5): 458-464, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30730059

RESUMO

This study focuses on the effect of iron on hexose transporters which perform glucose uptake. For this aim, we investigated the role of iron in glucose utilization and expression of hexose transporters in Schizosaccharomyces pombe. We applied different iron concentrations (1, 2, 5, 10 mM) to the cells grown up to mid-logarithmic phase. According to analysis of cell viability and morphology, we determined 2 mM and 5 mM as non-toxic and toxic doses, respectively. Besides, glucose consumption efficiency increased (1.5-fold) in the cells which were exposed to these iron concentrations. qRT-PCR analysis of hexose transporter genes showed that the expression of ght2 and ght8 genes were downregulated under both non-toxic and toxic iron conditions, but that of ght5 gene was significantly decreased only by toxic iron dose. In conclusion, it was suggested for the first time in this study that the Ght5 protein, as being high affinity hexose transporter, might play a role in sensing and signaling of iron stress.


Assuntos
Ferro/farmacologia , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Schizosaccharomyces pombe/genética , Schizosaccharomyces/efeitos dos fármacos , Transporte Biológico , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Ferro/toxicidade , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Schizosaccharomyces/genética , Schizosaccharomyces/crescimento & desenvolvimento , Schizosaccharomyces/metabolismo , Estresse Fisiológico/genética
19.
Ultrason Sonochem ; 53: 68-76, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30600211

RESUMO

For the first time, the inactivation of Microcystis aeruginosa using sono-Fenton process at low frequency high intensity (20 kHz, 0.42 W/mL) and high frequency low intensity (800 kHz, 0.07 W/mL) was investigated, respectively. 20 kHz sono-Fenton treatment successfully reduced cyanobacterial cell number from 4.19 × 106 cells/mL to 0.45 × 106 cells/mL within 5 min treatment. Alternatively, efficient performance of 800 kHz sono-Fenton process was observed to decrease Microcystis cell number to 2.33 × 106 cells/mL after 5 min inactivation, with lower energy cost. It was found that powerful 20 kHz sonication induced pore formation on the cell wall, leading to extracellular damage, while 800 kHz irradiation with low intensity triggered intracellular uptake of chemicals, suggesting endocytosis effects. Furthermore, sono-Fenton Processes were found to be affected by the concentrations of Fenton's reagent, and pre-sonication time. Although solo Fenton treatment released microcystins in water, the degradation of microcystin-LR were achieved using 20 and 800 kHz sono-Fenton processes, respectively. The results of this work showed that severe extracellular oxidation is the vital inactivation mechanism of 20 kHz sono-Fenton process, while the internal oxidation caused by intracellularly delivered Fenton reagents is suggested to be the main cause of 800 kHz sono-Fenton inactivation, leading to much lower energy cost. This work provides alternative methods to control harmful cyanobacteria in water towards effective treatment.


Assuntos
Espaço Extracelular/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Espaço Intracelular/efeitos dos fármacos , Ferro/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Microcystis/efeitos dos fármacos , Microcystis/fisiologia , Sonicação , Relação Dose-Resposta a Droga , Espaço Extracelular/metabolismo , Espaço Intracelular/metabolismo , Microcystis/citologia , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
20.
Future Med Chem ; 11(2): 119-135, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30644327

RESUMO

Despite improvements in the 5-year survival rate to over 80% in cancers, such as Hodgkin lymphoma and testicular cancer, more aggressive tumors including pancreatic and brain cancer still have extremely low survival rates. The establishment of chemoresistance, responsible for the reduction in treatment efficiency and cancer relapse, is one possible explanation for this setback. Metal-based compounds, a class of anticancer drugs, are largely used in the treatment of cancer. Herein, we will review the use of metal-based small molecules in chemotherapy, focusing on recent studies, and we will discuss how new nonplatinum-based agents are prompting scientists to increase drug specificity to overcome chemoresistance in cancer cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Metais/química , Metais/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Carboplatina/química , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Cisplatino/química , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Cobre/química , Cobre/farmacologia , Cobre/uso terapêutico , Descoberta de Drogas , Ouro/química , Ouro/farmacologia , Ouro/uso terapêutico , Humanos , Irídio/química , Irídio/farmacologia , Irídio/uso terapêutico , Ferro/química , Ferro/farmacologia , Ferro/uso terapêutico , Metais/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Rênio/química , Rênio/farmacologia , Rênio/uso terapêutico , Ródio/química , Ródio/farmacologia , Ródio/uso terapêutico , Rutênio/química , Rutênio/farmacologia , Rutênio/uso terapêutico
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