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1.
F1000Res ; 9: 674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123349

RESUMO

Background: The ability to protect workers and healthcare professionals from infection by SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is of great concern. Hospitals, nursing homes and employers are adopting infection control strategies based on guidance from leading public health organizations such as the CDC, OSHA, FDA, and other government bodies. Certain hard surface disinfectants are effective against SARS-CoV-2 but are not suitable for use on skin or personal protective equipment (PPE) that comes into contact with skin. Furthermore, near-ubiquitous alcohol-based hand sanitizers are acceptable for use on skin, but they are not suitable for use on PPE. PPE, especially masks, are also commonly being used for longer durations than normal. There is a need for new products and techniques that can effectively disinfect PPE during wear time without having detrimental effects on surrounding skin. Clyraguard spray is a novel copper iodine complex designed to be used on non-critical PPE. Methods: In this study, the Clyraguard copper iodine complex was tested for its ability to inactivate SARS-CoV-2 in solution. Results: These data indicate the product to be effective in reducing SARS-CoV-2 titers in a time-dependent manner, with the virus being reduced below the detection limits within 30 minutes. Conclusions: These results suggest that Clyraguard may be an effective tool for mitigating cross-contamination of non-critical PPE that may come into contact with SARS-CoV-2.


Assuntos
Betacoronavirus/efeitos dos fármacos , Cobre/farmacologia , Desinfetantes/farmacologia , Iodo/farmacologia , Inativação de Vírus/efeitos dos fármacos , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral
2.
Mutat Res ; 856-857: 503217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928365

RESUMO

We studied the genotoxicity and cellular uptake of nanosized (<50 nm) and fine (<10 µm) copper oxide (CuO) particles in vitro in human bronchial epithelial (BEAS-2B) cells. In addition, the effect of dispersing the particles using bovine serum albumin (BSA) on DNA damage induction was investigated. DNA damage was assessed by the alkaline comet (single cell gel electrophoresis) assay after 3-h, 6-h and 24-h exposures. The cytokinesis-block micronucleus assay was applied to study chromosome damage. Both fine- and nanosized CuO particles induced a dose-dependent increase in DNA damage at all timepoints tested. However, nanosized CuO damaged DNA at lower doses and higher levels compared with fine CuO. Dispersing the nanoparticles in the presence of BSA (0.6 mg/mL) resulted in a small and inconsistent decrease in DNA damage compared with dispersions in serum-free cell culture medium only. CuO nanoparticles induced a clear dose-dependent increase in micronucleated cells at doses that strongly increased cytostasis and were markedly cytotoxic at 24 and 48 h. Fine CuO showed a slight induction of micronuclei. Hyperspectral microscopy indicated a substantial cellular uptake of both types of particles after a 3-h exposure to a dose of 20 µg/cm2. The number of particles internalized by the cells was higher for nanosized than fine CuO, as quantified by the frequency of spectral matches in the total cell area and by the number of spectrally matched visible particles or agglomerates per cell. The particle uptake was limited by particle size. The stronger genotoxic activity of nanosized than fine CuO particles is likely to derive from the higher cellular uptake and more effective intracellular dissolution of nanoparticles.


Assuntos
Brônquios/efeitos dos fármacos , Cobre/farmacologia , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Humanos , Nanopartículas Metálicas/química , Mutagênicos/química , Mutagênicos/farmacologia , Tamanho da Partícula , Análise de Célula Única
3.
Mutat Res ; 856-857: 503231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928371

RESUMO

Heavy metals are widely used in many industries in Thailand and found in the environment. Occupational exposure to heavy metals is often chronic and caused by environmental contaminations, potentially leading to mutations and cancer. Although the genotoxic effects of occupational exposure to multiple heavy metals have been extensively studied, the findings regarding their genotoxicity are conflicting. In this study, we focused on investigating the genotoxic effects of certain heavy metals mixtures, including lead (Pb), copper (Cu), zinc (Zn), and tin (Sn), to which workers are exposed in the manufacturing industry. The cytokinesis-blocked micronucleus (CBMN) assay in peripheral blood lymphocytes was performed, and DNA damage was assessed by measuring tumour-associated protein levels and 8-hydroxy-2'-deoxyguanosine (8-OHdG) generated by oxidative stress that causes cytotoxicity. The occupational exposure group included 110 workers exposed to heavy metal mixtures and 105 matched control subjects. We found statistically significant differences in the blood Pb, Sn, and Cu levels between the exposed workers and the control subjects (p < 0.001). Analysis of micronuclei (MN) in peripheral blood lymphocytes revealed a significantly increased frequency of MN in exposed workers compared with that in control subjects (p<0.05). Non-smoking exposed workers were selected for 8-OHdG formation and mutant p53 tests, and significant differences in the mean plasma 8-OHdG concentration (p < 0.001) were found between the occupational exposure and the control group, but no differences were found in the levels of mutant p53. Thus, chronic exposure to different heavy metals causes genotoxic effects in humans. Furthermore, the CBMN assay and 8-OHdG formation can be used as surrogate biomarkers to identify and monitor groups with higher carcinogenic risk in the early stages of toxicity. In summary, our results indicate that mixtures of heavy metals (Pb, Sn, and Cu) in manufacturing industries pose an elevated health risk due to DNA damage.


Assuntos
Dano ao DNA/efeitos dos fármacos , Metais Pesados/toxicidade , Mutagênese/efeitos dos fármacos , Mutagênicos/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Cobre/farmacologia , Cobre/toxicidade , Citocinese/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Chumbo/farmacologia , Chumbo/toxicidade , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Masculino , Indústria Manufatureira , Metais Pesados/farmacologia , Testes para Micronúcleos , Pessoa de Meia-Idade , Mutagênicos/farmacologia , Proteína Supressora de Tumor p53
4.
PLoS One ; 15(9): e0239774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976506

RESUMO

We found the mineralization of Cu during long-term Cu2+ adsorption onto dry baker's yeast cells phosphorylated using sodium cyclo-triphosphate. Field emission scanning electron microscopy (FESEM) with energy-dispersive X-ray spectroscopy confirmed that the elemental composition of minerals were copper, phosphorus, and oxygen. Synchrotron-based X-ray absorption fine structure showed that the local structure around Cu atoms deposited on the mineral was almost identical to that of commercial copper (II) phosphate Cu3(PO4)2∙3H2O. However, the crystallinity was low, and the structure was slightly distorted. Time profile analysis using FESEM revealed that copper phosphate mineralization was first apparent on Day 3 of adsorption, whereas mineral formation plateaued at around Day 7. It seems that mineralization occurs by the local saturation of phosphate and Cu2+ on the yeast cells. Mineralization of the rare earth ion Dy3+ was also demonstrated during long-term adsorption. Mineralization on phosphorylated yeast cells appears to follow a common path for various types of metal ions and provides a promising technique for metal recovery via irreversible adsorption.


Assuntos
Cobre/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Adsorção , Cristalização , Dessecação , Oxigênio/metabolismo , Fósforo/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura
5.
PLoS Pathog ; 16(8): e1008856, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32845936

RESUMO

Copper and superoxide are used by the phagocytes to kill bacteria. Copper is a host effector encountered by uropathogenic Escherichia coli (UPEC) during urinary tract infection in a non-human primate model, and in humans. UPEC is exposed to higher levels of copper in the gut prior to entering the urinary tract. Effects of pre-exposure to copper on bacterial killing by superoxide has not been reported. We hypothesized that copper-replete E. coli is more sensitive to killing by superoxide in vitro, and in activated macrophages. We utilized wild-type UPEC strain CFT073, and its isogenic mutants lacking copper efflux systems, superoxide dismutases (SODs), regulators of a superoxide dismutase, and complemented mutants to address this question. Surprisingly, our results reveal that copper protects UPEC against killing by superoxide in vitro. This copper-dependent protection was amplified in the mutants lacking copper efflux systems. Increased levels of copper and manganese were detected in UPEC exposed to sublethal concentration of copper. Copper activated the transcription of sodA in a SoxR- and SoxS-dependent manner resulting in enhanced levels of SodA activity. Importantly, pre-exposure to copper increased the survival of UPEC within RAW264.7 and bone marrow-derived murine macrophages. Loss of SodA, but not SodB or SodC, in UPEC obliterated copper-dependent protection from superoxide in vitro, and from killing within macrophages. Collectively, our results suggest a model in which sublethal levels of copper trigger the activation of SodA and SodC through independent mechanisms that converge to promote the survival of UPEC from killing by superoxide. A major implication of our findings is that bacteria colonizing copper-rich milieus are primed for efficient detoxification of superoxide.


Assuntos
Cobre/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxidos/toxicidade , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/efeitos dos fármacos , Animais , Infecções por Escherichia coli/induzido quimicamente , Infecções por Escherichia coli/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Superóxido Dismutase/genética , Infecções Urinárias/induzido quimicamente , Infecções Urinárias/microbiologia
6.
Int J Nanomedicine ; 15: 3983-3999, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606660

RESUMO

Introduction: In recent years, the use of cost-effective, multifunctional, environmentally friendly and simple prepared nanomaterials/nanoparticles have been emerged considerably. In this manner, different synthesizing methods were reported and optimized, but there is still lack of a comprehensive method with multifunctional properties. Materials and Methods: In this study, we aim to synthesis the copper oxide nanoparticles using Achillea millefolium leaf extracts for the first time. Catalytic activity was investigated by in situ azide alkyne cycloaddition click and also A3 coupling reaction, and optimized in terms of temperature, solvent, and time of the reaction. Furthermore, the photocatalytic activity of the synthesized nanoparticles was screened in terms of degradation methylene blue dye. Biological activity of the synthesized nanoparticles was evaluated in terms of antibacterial and anti-fungal assessments against Staphylococcus aureus, M. tuberculosis, E. coli, K. pneumoniae, P. mirabili, C. diphtheriae and S. pyogenes bacteria's and G. albicans, A. flavus, M. canis and G. glabrata fungus. In the next step, the biosynthesized CuO-NPs were screened by MTT and NTU assays. Results: Based on our knowledge, this is a comprehensive study on the catalytic and biological activity of copper oxide nanoparticles synthesizing from Achillea millefolium, which presents great and significant results (in both catalytic and biological activities) based on a simple and green procedure. Conclusion: Comprehensive biomedical and catalytic investigation of the biosynthesized CuO-NPs showed the mentioned method leads to synthesis of more eco-friendly nanoparticles. The in vitro studies showed promising and considerable results, and due to the great stability of these nanoparticles in a green media, effective biological activity considered as an advantageous.


Assuntos
Tecnologia Biomédica , Cobre/farmacologia , Nanopartículas Metálicas/química , Achillea/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Catálise , Sobrevivência Celular/efeitos dos fármacos , Reação de Cicloadição , Fungos/efeitos dos fármacos , Células Hep G2 , Humanos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Solventes/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Fatores de Tempo , Difração de Raios X
7.
PLoS One ; 15(7): e0234964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614844

RESUMO

In this study, a facile, ecological and economical green method is described for the fabrication of iron (Fe), copper (Cu) and silver (Ag) nanoparticles (NPs) from the extract of Syzygium cumini leaves. The obtained metal NPs were categorized using UV/Vis, SEM, TEM, FTIR and EDX-ray spectroscopy techniques. The Fe-, Cu- and Ag-NPs were crystalline, spherical and size ranged from 40-52, 28-35 and 11-19 nm, respectively. The Ag-NPs showed excellent antimicrobial activities against methicillin- and vancomycin-resistance Staphylococcus aureus bacterial strains and Aspergillus flavus and A. parasiticus fungal species. Furthermore, the aflatoxins (AFs) production was also significantly inhibited when compared with the Fe- and Cu-NPs. In contrast, the adsorption results of NPs with aflatoxin B1 (AFB1) were observed as following order Fe->Cu->Ag-NPs. The Langmuir isotherm model well described the equilibrium data by the sorption capacity of Fe-NPs (105.3 ng mg-1), Cu-NPs (88.5 ng mg-1) and Ag-NPs (81.7 ng mg-1). The adsorption was found feasible, endothermic and follow the pseudo-second order kinetic model as revealed by the thermodynamic and kinetic studies. The present findings suggests that the green synthesis of metal NPs is a simple, sustainable, non-toxic, economical and energy-effective as compared to the others conventional approaches. In addition, synthesized metal NPs might be a promising AFs adsorbent for the detoxification of AFB1 in human and animal food/feed.


Assuntos
Aflatoxina B1/isolamento & purificação , Anti-Infecciosos/metabolismo , Biotecnologia/métodos , Cobre , Química Verde/métodos , Ferro , Nanopartículas Metálicas , Extratos Vegetais/metabolismo , Folhas de Planta/metabolismo , Prata , Desintoxicação por Sorção , Syzygium/metabolismo , Adsorção , Anti-Infecciosos/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus flavus/efeitos dos fármacos , Técnicas de Química Analítica , Cobre/administração & dosagem , Cobre/farmacologia , Resistência Microbiana a Medicamentos , Ferro/administração & dosagem , Ferro/farmacologia , Cinética , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxirredução , Prata/administração & dosagem , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Termodinâmica , Vancomicina/farmacologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-32580091

RESUMO

Little information is available on the interaction of CuO nanoparticles (nCuO) with tuberous roots. In this study, Beauregard-14 (B-14, low lignin) and Covington (COV, high lignin) sweetpotato varieties were cultivated until maturity in soil amended with nCuO, bulk copper oxide (bCuO) and CuCl2 at 25-125 mg/kg. The Cu treatments had no significant influence on chlorophyll content. Gas exchange parameters were not affected in B-14. In COV, however, at 125 mg/kg treatments, bCuO reduced the intercellular CO2 (11%), while CuCl2 increased it by 7%, compared with control (p ≤ 0.035). At 25 mg/kg nCuO increased the length of COV roots (20.7 ± 2.0 cm vs. 14.6 ± 0.8 cm, p ≤ 0.05). In periderm of B-14, nCuO, at 125 mg/kg, increased Mg by 232%, while the equivalent concentration of CuCl2 reduced P by 410%, compared with control (p ≤ 0.05). The data suggest the potential application of nCuO as nanofertilizer for sweetpotato storage root production.


Assuntos
Cobre/farmacologia , Ipomoea batatas/efeitos dos fármacos , Nanopartículas Metálicas , Raízes de Plantas/efeitos dos fármacos , Óxidos , Solo
9.
AAPS PharmSciTech ; 21(5): 175, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32556636

RESUMO

Wound-healing is a very complex and evolutionary process that involves a great variety of dynamic steps. Although different pharmaceutical agents have been developed to hasten the wound-healing process, the existing agents are still far from optimal. The present work aimed to prepare and evaluate the wound-healing efficacy of phenytoin-loaded copper nanoparticles (PHT-loaded CuNPs). CuNPs were biosynthesized using licorice aqueous extract. The prepared CuNPs were loaded with PHT by adsorption, characterized, and evaluated for wound-healing efficiency. Results showed that both plain and PHT-loaded CuNPs were monodisperse and exhibited a cubic and hexagonal morphology. The mechanism by which PHT was adsorbed on the surface of CuNPs was best fit by the Langmuir model with a maximum loaded monolayer capacity of 181 mg/g. The kinetic study revealed that the adsorption reaction followed the pseudo-second order while the thermodynamic parameters indicated that the adsorption process was physical in nature and endothermic, and occurred spontaneously. Moreover, the in vivo wound-healing activity of PHT-loaded CuNP impregnated hydroxypropylmethyl cellulose (HPMC) gel was carried out using an excisional wound model in rats. Data showed that PHT-loaded CuNPs accelerated epidermal regeneration and stimulated granulation and tissue formation in treated rats compared to controls. Additionally, quantitative real-time polymerase chain reaction (RT-PCR) analysis showed that lesions treated with PHT-loaded CuNPs were associated with a marked increase in the expression of dermal procollagen type I and a decrease in the expression of the inflammatory JAK3 compared to control samples. In conclusion, PHT-loaded CuNPs are a promising platform for effective and rapid wound-healing.


Assuntos
Cobre/farmacologia , Nanopartículas , Fenitoína/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Colágeno Tipo I/metabolismo , Janus Quinase 3/metabolismo , Masculino , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/patologia
10.
Int J Nanomedicine ; 15: 3161-3180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440116

RESUMO

Aim: With the rapid emergence of antibiotic resistance, efforts are being made to obtain new selective antimicrobial agents. Hybridization between quinazolinone and benzenesulfonamide can provide new antimicrobial candidates. Also, the use of nanoparticles can help boost drug efficacy and lower side effects. Materials and Methods: Novel quinazolinone-benzenesulfonamide derivatives 5-18 were synthesized and screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, MRSA and yeast. The most potent compound 16 was conjugated with copper oxide nanoparticles 16-CuONPs by gamma irradiation (4.5 KGy). Characterization was performed using UV-Visible, TEM examination, XRD patterns and DLS. Moreover, compound 16 was used to synthesize two nanoformulations: 16-CNPs by loading 16 in chitosan nanoparticles and the nanocomposites 16-CuONPs-CNPs. Characterization of these nanoformulations was performed using TEM and zeta potential. Besides, the inhibitory profile against Staphylococcus aureus DNA gyrase was assayed. Cytotoxic evaluation of 16, 16-CNPs and 16-CuONPs-CNPs on normal VERO cell line was carried out to determine its relative safety. Molecular docking of 16 was performed inside the active site of S. aureus DNA gyrase. Results: Compound 16 was the most active in this series against all the tested strains and showed inhibition zones and MICs in the ranges of 25-36 mm and 0.31-5.0 µg/mL, respectively. The antimicrobial screening of the synthesized nanoformulations revealed that 16-CuONPs-CNPs displayed the most potent activity. The MBCs of 16 and the nanoformulations were measured and proved their bactericidal mode of action. The inhibitory profile against S. aureus DNA gyrase showed IC50 ranging from 10.57 to 27.32 µM. Cytotoxic evaluation of 16, 16-CNPs and 16-CuONPs-CNPs against normal VERO cell lines proved its relative safety (IC50= 927, 543 and 637 µg/mL, respectively). Molecular docking of 16 inside the active site of S. aureus DNA gyrase showed that it binds in the same manner as that of the co-crystallized ligand, ciprofloxacin. Conclusion: Compound 16 could be considered as a new antimicrobial lead candidate with enhanced activity upon nanoformulation.


Assuntos
Antibacterianos/farmacologia , Quinazolinonas/farmacologia , Sulfonamidas/farmacologia , Tioacetamida/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Cobre/farmacologia , DNA Girase/metabolismo , Raios gama , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Quinazolinonas/síntese química , Quinazolinonas/química , Sulfonamidas/síntese química , Sulfonamidas/química , Tioacetamida/síntese química , Tioacetamida/química , Inibidores da Topoisomerase II/farmacologia
11.
Chemosphere ; 253: 126654, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464761

RESUMO

Heme oxygenase-1(HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis. In the present study, the full sequence of HO-1 was cloned from golden pompano(Trachinotus ovatus) by RT-PCR and RACE-PCR. The full cDNA sequence of HO-1 was 1349 bp in length which comprised of a 726 bp open reading frame (ORF) preceded by 262 bp 5'-untranslated region (UTR), and followed by a 360 bp 3'UTR, encoding 241 amino acid residues. Phylogenetic analysis revealed that HO-1 showed highest similarity to that of Takifugu rubripes. Tissue distribution analysis showed that the expression level of HO-1 was relatively high in heart, liver and spleen. A trial was conducted to investigate the response of Nrf2/HO-1 signaling pathway to oxidative stress induced by copper. The results showed that mRNA expression of NF-E2-related nuclear factor2 (Nrf2), Kelch-like-ECH-associated protein1 (keap1), superoxide dismutase (SOD), catalase (CAT), HO-1, NAD(P)H quinone oxidoreductase 1 (NQO1) and Glutathione peroxidase (GSH-PX) all significantly increased in copper treated group than that in the control group. This work provides new insight into the molecular mechanism underlying the Nrf2/HO-1 pathway in oxidative response in T. ovatus.


Assuntos
Cobre/farmacologia , Heme Oxigenase-1/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Perciformes/metabolismo , Transdução de Sinais , Animais , Antioxidantes/metabolismo , Heme Oxigenase-1/metabolismo , Oxirredutases/metabolismo , Análise de Sequência de DNA , Distribuição Tecidual
12.
Int J Nanomedicine ; 15: 2541-2553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368039

RESUMO

Background: In the emerging field of nanotechnology, copper oxide (CuO) nanomaterials are considered to be one of the most important transition metal oxides owing to its fascinating properties. Its synthesis from green chemistry principles is gaining importance as next-generation antibiotics due to its simplicity, eco-friendliness, and cost-effectiveness. In the present study, CuO nanorods (CuO NRs) were synthesized from the aqueous fruit extract of Momordica charantia and characterized using different analytical techniques. Further, the biomedical therapeutic potential was evaluated against multi-drug resistant microbial strains. Materials and Methods: To synthesize CuO NRs, 0.1M of CuSO4.5H2O solution was added to aqueous extract of Momordica charantia in a 1:3 (v/v) ratio (pH=11) and heated at 50°C followed by washing and drying. The synthesized CuO NRs were subjected to characterization using different analytical techniques such as UV visible spectroscopy, zeta sizer equipped with zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). Further, the application as a biomedical therapeutic potential was evaluated in vitro using well diffusion method against eleven multidrug-resistant clinical bacterial strains, a fungus- Trichophyton rubrum and in ovo against the R2B virus using haemagglutination (HA) test. Results: Characterization was preliminarily done by the spectral study that confirms the absorbance band at 245nm. FTIR analysis at 628 cm-1 peak identified copper oxide vibration. SEM analysis revealed agglomerated particle clusters. However, with TEM clear nanorods of average diameter of 61.48 ± 2 nm were observed. EDAX confirmed CuO formation while XRD showed a typical monoclinic structure with 6 nm crystallite size. Biological screening of CuO NRs showed significant results against both in vitro and in ovo methods. Significant inhibitory activity (p<0.0001) was noted against most of the resistant human pathogenic strains including both Gram-positive and Gram-negative bacteria. The highest efficacy was observed against Bacillus cereus with a 31.66 mm zone of inhibition. Besides, the therapeutic potential of CuO NRs against Corynebacterium xerosis, Streptococcus viridians and R2B strain of Newcastle disease is reported for the first time. Conclusion: Based on the present results, it could be expected that green synthesized CuO NRs would find potential applications in the field of nanomedicine.


Assuntos
Antibacterianos/farmacologia , Cobre/farmacologia , Química Verde , Momordica charantia/química , Nanoestruturas/química , Animais , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Galinhas , Fungos/efeitos dos fármacos , Testes de Hemaglutinação , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Tamanho da Partícula , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Difração de Raios X
13.
PLoS One ; 15(5): e0226859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437348

RESUMO

INTRODUCTION: Larvicide application in ovitrap is one of the currently available methods used in mosquito eradication campaign. We previously reported that copper in liquid form is a promising candidate due to its potent larvicide properties in a laboratory setting and in the field. In the field study, several larvae survived in outdoor ovitrap due to the dilution of copper concentration by rainwater. The surviving larvae were smaller and less motile. This led our interest to study the effect of a sub-lethal dose of copper in ovitrap on mosquito larval development, pupation time and lifespan in the adult stage. METHODS: First instar larvae of Aedes albopictus, Anopheles stephensi, and Culex pipiens were put in water containing 0.15 ppm, 0.30 ppm, and 0.60 ppm of copper. The surviving larvae, the emerging pupae, and adult mosquitoes were observed and counted every 24-hour and statistically analyzed by t-test or Mann-Whitney U test. Inter-species difference in response to different concentration of copper were also analyzed. RESULTS: Copper showed a potent larvicide effect at 0.60 ppm concentration. Prolonged pupation time and a lower number of adult mosquitoes were observed at 0.15 ppm concentration. Copper exposure did not affect adult mosquitoes' lifespan. Culex pipiens was the most susceptible species to copper exposure. CONCLUSION: This study demonstrates the efficacy of copper at <1 ppm to kill mosquito larvae and to prolong pupation and adult emergence time. Utilization of copper at a low concentration is cost-efficient in the public health setting and remains an open option as an environmentally safe vector control strategy.


Assuntos
Cobre/farmacologia , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Aedes/efeitos dos fármacos , Animais , Anopheles/efeitos dos fármacos , Culex/efeitos dos fármacos
14.
PLoS One ; 15(4): e0231276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275737

RESUMO

OBJECTIVES: Alloyed metallic nanoparticles of silver and copper are effective against intracellular infection. However, systemic toxicity may arise due to the non-specific delivery of the nanoparticles. In addressing the issue, this study deals with the targeting of silver-copper-boron (ACB) nanoparticles to infected osteoblasts, which could decrease systemic toxicity and form the basis of targeting specific markers expressed in bone infections. METHODS: ACB nanoparticles were synthesized and conjugated to the Cadherin-11 antibody (OBAb). The effect of targeting nanoparticles against extracellular and intracellular S. aureus was determined by enumeration of bacterial growth. The binding of the targeting nanoparticles to infected osteoblasts as well as the visualization of live/dead bacteria due to treatment was carried out using fluorescence microscopy. MTT assay was used to determine the viability of osteoblasts with different concentrations of the nanoparticles. RESULTS: The ACB nanoparticles conjugated to OBAb (ACB-OBAb) were effective against extracellular S. aureus. The ACB-OBAb nanoparticles showed a 1.32 log reduction of intracellular S. aureus at a concentration of 1mg/L. The ACB-OBAb nanoparticles were able to bind to the infected osteoblast and showed toxicity to osteoblasts at levels ≥20mg/L. Also, the percentage of silver, copper, and boron in the nanoparticles determined the effectiveness of their antibacterial activity. CONCLUSION: The ACB-OBAb nanoparticles were able to target the osteoblasts and demonstrated significant antibacterial activity against intracellular S. aureus. Targeting shows promise as a strategy to target specific markers expressed on infected osteoblasts for efficient nanoparticle delivery, and further animal studies are recommended to test its efficacy in vivo.


Assuntos
Ligas/farmacologia , Osso e Ossos/citologia , Boro/farmacologia , Cobre/farmacologia , Espaço Intracelular/microbiologia , Nanopartículas Metálicas/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Caderinas/imunologia , Linhagem Celular , Endocitose/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Osteoblastos/efeitos dos fármacos , Osteoblastos/microbiologia
15.
J Anim Sci ; 98(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32277238

RESUMO

A 42-d experiment was conducted to evaluate the effect of Cu and Zn source and Cu level on pig performance, mineral status, bacterial modulation, and the presence of antimicrobial-resistant genes in isolates of Enterococcus spp. At weaning, 528 pigs (5.9 ± 0.50 kg) were allotted to 48 pens of a randomized complete block design in a 2 × 2 factorial arrangement with two Cu and Zn sources (SF: sulfate and HCl: hydroxychloride) and two Cu levels (15 and 160 mg/kg). As a challenge, the pigs were reared in dirty pens used by a previous commercial batch. Two-phase diets were offered: the pre-starter (PS) phase from day 1 to 14 and the starter phase (ST) from day 14 to 42. At days 14 and 42, pigs were individually weighed and blood samples from one pig per pen were taken. At the end of the experiment, one pig per pen was euthanized to collect the samples. Feeding high levels of Cu increased body weight (BW) from 16.6 to 17.7 kg (P < 0.001). Furthermore, average daily gain, gain to feed (G:F) ratio, average daily feed intake (ADFI), and mineral status were enhanced with Cu at 160 mg/kg (P < 0.05) compared with Cu at 15 mg/kg. There was no effect of the interaction between source × level on any of the growth performance responses except for ADFI (P = 0.004) and G:F (P = 0.029) at the end of the ST period and for G:F (P = 0.006) for entire nursery period (day 0 to 42). At the end of the ST period, pigs fed Cu at 160 mg/kg as HCl had not only higher ADFI but also lower G:F than those fed Cu as SF at 160 mg/kg. Meanwhile, for the entire nursery period, G:F did not differ between pigs fed Cu at 160 mg/kg as HCl or SF. In colonic digesta, the relative abundance of Streptococcus, Enterobacter, Escherichia, among others, decreased (P-adjust < 0.05), while Lachnospira and Roseburia tended (P-adjust < 0.10) to increase in pigs fed Cu at 160 mg/kg as HCl compared with those fed Cu SF at 160 mg/kg. An increase (P-adjust < 0.05) in Methanosphaera and Roseburia was observed in pigs fed Cu at 160 mg/kg. From colon digesta, Enterococcus spp. was isolated in 40 samples, being E. faecalis the most dominating (65%) regardless of the experimental diet. Genes of ermB (7.5%) and tetM (5%) were identified. No genes for Cu (tcrB) or vancomycin (vanA, vanB, vanC1, and vanC2) were detected. In conclusion, European Union permissible levels of Cu (160 mg/kg), of both sources, were able to increase performance, mineral status, and bacterial modulation compared with nutritional level. Different effects on growth performance, mineral tissue content, and microbial modulation were observed between Cu and Zn sources.


Assuntos
Cobre/farmacologia , Farmacorresistência Bacteriana/genética , Enterococcus/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Suínos/fisiologia , Zinco/farmacologia , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Enterococcus/isolamento & purificação , Feminino , Microbioma Gastrointestinal/genética , Masculino , Distribuição Aleatória , Suínos/genética , Suínos/crescimento & desenvolvimento , Suínos/microbiologia , Desmame
16.
Bratisl Lek Listy ; 121(3): 211-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115979

RESUMO

OBJECTIVES: Betanin and copper sulphate have been previously indicated as beneficial agents for ischemia/reperfusion (I/R) as antioxidant compounds in various models. We investigated whether betanin and copper have any protective effects on the heart and lung against I/R injury in rats. METHODS: Spraque-Dawley rats were assigned in groups: Sham (laparotomy only), control (I/R only), betanin treatment (100 mg/kg of betanin administered intraperitoneally (i.p.) 60 minutes before I/R) and copper sulfate treatment group (0.1 mg/kg/day copper sulfate i.p. for 7 days before I/R). Ischemia was induced by clamping the aorta between the left renal artery and aortic bifurcation for 45 minutes. After 48-hour reperfusion, the rats were sacrificed and heart/lung tissues were harvested. Malondialdehyde (MDA), myeloperoxidase (MPO), interleukin 6 (IL-6) levels were determined. Apoptosis was determined via TUNEL assay. RESULTS: MDA, MPO, IL-6 levels and apoptotic cells were significantly increased in the I/R group. In both treatment groups, MDA and MPO levels were decreased. IL-6 was significantly decreased in response to betanin administration in the heart, but not in the lung; copper had no effect in either area. The numbers of apoptotic cells were significantly decreased in both treatment groups. CONCLUSION: Betanin and copper may have protective effects on I/R injury in the heart and lung in rats (Fig. 6, Ref. 39).


Assuntos
Betacianinas , Cobre , Traumatismo por Reperfusão , Animais , Betacianinas/farmacologia , Cobre/farmacologia , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Malondialdeído , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle
17.
Artigo em Inglês | MEDLINE | ID: mdl-32130071

RESUMO

Proper amounts of copper supplemented in livestock feed improve the physical growth and traits of farm animals. The pancreas is an important organ with both exocrine and endocrine portions. To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock.


Assuntos
Cobre/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ductos Pancreáticos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Proteínas de Transporte de Cátions/metabolismo , Proliferação de Células/efeitos dos fármacos , Cobre/metabolismo , Proteínas de Transporte de Cobre/metabolismo , Organoides/metabolismo , Ductos Pancreáticos/metabolismo , Ovinos
18.
Environ Monit Assess ; 192(4): 232, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166379

RESUMO

Copper oxide nanoparticles (CuO NPs) have been extensively explored for use in agriculture. Previous studies have indicated that application of CuO NPs might be promising for development and conservation of plants, pest control, and for the recovery of degraded soils. However, depending on the applied concentration copper can cause phytotoxic effects. In this work, biosynthesized CuO NPs (using green tea extract) were evaluated on their effects on lettuce (Lactuca sativa L.) seedling growth, which were exposed at concentrations ranged between 0.2 and 300 µg mL-1. From the biosynthesized were obtained ultra-small CuO NPs (~ 6.6 nm), with high stability in aqueous suspension. Toxicity bioassays have shown that at low concentrations (up to 40 µg mL-1), CuO NPs did not affect or even enhanced the seed germination. At higher concentrations (higher than 40 µg mL-1), inhibition of seed germination and radicle growth ranging from 35 to 75% was observed. With the increase of CuO NPs concentrations, nitrite and S-nitrosothiols levels in radicles increased, whereas superoxide dismutase and total antioxidant activities decreased. The nitrite and S-nitrosothiols levels in lettuce radicles showed a direct dose response to CuO NP application, which may indicate nitric oxide-dependent signaling pathways in the plant responses. Therefore, the results demonstrated that at low concentrations (≤ 20 µg mL-1) of CuO NPs, beneficial effects are obtained from seedlings, enhancing plant growth, and the involvement of nitric oxide signaling in the phytotoxic effects induced by high concentration of this formulation. Graphical abstract.


Assuntos
Cobre , Alface , Nanopartículas Metálicas , Nanopartículas , Antioxidantes , Cobre/farmacologia , Monitoramento Ambiental , Alface/efeitos dos fármacos , Alface/crescimento & desenvolvimento , Óxido Nítrico , Plântula
19.
Sci Rep ; 10(1): 3737, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111947

RESUMO

Encapsulated bioactive agents applied to the Lactuca sativa L. present an innovative approach to stimulate the production of plant secondary metabolites increasing its nutritive value. Calcium and copper ions were encapsulated in biopolymeric microparticles (microspheres and microcapsules) either as single agents or in combination with biocontrol agents, Trichoderma viride spores, a fungal plant growth mediator. Both, calcium and copper ions are directly involved in the synthesis of plant secondary metabolites and alongside, Trichoderma viride can provide indirect stimulation and higher uptake of nutrients. All treatments with microparticles had a positive effect on the enhancement of plant secondary metabolites content in Lactuca sativa L. The highest increase of chlorophylls, antioxidant activity and phenolic was obtained by calcium-based microparticles in both, conventionally and hydroponically grown lettuces. Non-encapsulated fungus Trichoderma viride enhanced the synthesis of plant secondary metabolites only in hydroponics cultivation signifying the importance of its encapsulation. Encapsulation proved to be simple, sustainable and environmentally favorable for the production of lettuce with increased nutritional quality, which is lettuce fortified with important bioactive compounds.


Assuntos
Cálcio/farmacologia , Cobre/farmacologia , Alface , Doenças das Plantas/microbiologia , Folhas de Planta , Esporos Fúngicos/crescimento & desenvolvimento , Trichoderma/crescimento & desenvolvimento , Cápsulas , Alface/metabolismo , Alface/microbiologia , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia
20.
Dalton Trans ; 49(13): 4100-4113, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32141470

RESUMO

In the current study, four novel mononuclear Cu(ii) complexes with terpyridine (L) and different co-ligands (phen, bipy, and imd) were synthesized and characterized in detail, where L is 4'-(3,4,5-trimethoxyphenyl)-2,2':6',2''-terpyridine. The identity and purity of all complexes were determined by elemental analysis, spectroscopic techniques (UV-vis, FTIR, ESI-MS, and EPR) and CV, including single crystal X-ray determination of three complexes ([Cu(L)(phen)](ClO4)2 (C-I), [Cu(L)2](ClO4)2 (C-II) and [Cu(L)(imd)(ClO4)](ClO4) (C-IV). DNA binding studies were performed using fluorescence assay and the binding constants were calculated using the Stern-Volmer equation and the modified Stern-Volmer equation. The magnitude of Kapp of all complexes was 105 M-1, indicating moderate intercalative binding between CT-DNA and the complexes. Agarose gel electrophoresis clearly reflected their ability to cleave a double stranded pET-28b plasmid in the presence of an external reducing agent (3-mercapto propionic acid). Steady-state fluorescence quenching was performed to understand their interactions with BSA. The studies suggested a mixed quenching mechanism with an initial static process. Furthermore, the antiproliferative activity of the complexes was evaluated against lung cancer A549 cells and primary mice splenocytes. Interestingly, the complexes show 25-200 fold greater toxicity towards the A549 cells than primary splenocytes, indicating their selectivity towards the former. The good binding behavior of all four complexes towards DNA and BSA and their cytotoxicity render these compounds promising potent anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , DNA/efeitos dos fármacos , Piridinas/farmacologia , Soroalbumina Bovina/efeitos dos fármacos , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Cristalografia por Raios X , DNA/química , Clivagem do DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Piridinas/química , Soroalbumina Bovina/química
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