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1.
Sci Rep ; 12(1): 2249, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145167

RESUMO

Super dosing copper (Cu) has long been used as an alternative to antibiotic growth-promoters in broiler chickens' diet to improve gut health. This study was designed to compare nutritional and growth-promoting levels of Cu hydroxychloride (CH) with CuSO4 on gut health bio-markers and liver mineral profile of broiler chickens. Ross 308 chicks (n = 864) were randomly assigned to eight treatments, as basal diet containing no supplemental Cu; the basal diet with 15 or 200 mg/kg Cu as CuSO4; or 15, 50, 100, 150 or 200 mg/kg Cu from CH. The highest liver Cu content was observed in birds fed the diets with 200 mg/kg CuSO4 (P < 0.01). Serum FITC-d concentration as the leaky gut marker, and liver malondialdehyde concentration were not affected. Copper level or source had no effect on cecal short chain fatty acid and the mRNA expression of five jejunal genes involved in gut integrity. Negative linear responses of Cu were observed on Lactobacillus (P = 0.032), Bacteroides (P = 0.033), and Enterobacteriaceae (P = 0.028) counts. The jejunal villus height increased in birds fed CH at 200 and 100 mg/kg (P < 0.05). Increasing Cu levels, linearly and quadratically (P < 0.001), increased Cu excretion.


Assuntos
Ceco/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Jejuno/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Ceco/microbiologia , Galinhas , Cobre/metabolismo , Suplementos Nutricionais , Jejuno/anatomia & histologia , Fígado/metabolismo , Masculino
2.
Plant Dis ; 106(3): 960-965, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34705489

RESUMO

Since the protective activity of the Bordeaux mixture against plant disease caused by oomycetes was discovered, copper compounds have been used for more than a century as an effective plant protection strategy. However, the application of excessive copper can cause adverse effects through long-term heavy metal accumulation in soils. Therefore, it is necessary to develop new strategies to reduce or replace copper in pesticides based on organic and low-input farming systems. Organic acids are eco-friendly. In this study, we tested the antifungal and anti-oomycete activity of maleic acid (MA) and copper sulfate (CS) against 13 plant pathogens. Treatment with a mixture of MA and CS showed strong anti-oomycetes activity against Phytophthora xcambivora, P. capsici, and P. cinnamomi. Moreover, the concentration of CS in the activated mixture of MA and CS was lower than that in the activated CS only, and the mixture showed synergy or partial synergy effects on the anti-oomycete activity. Application of a wettable powder formulation of MA and CS mixture (MCS 30WP; 26.67% MA and 3.33% CS) had excellent protective activity in pot experiments with control values of 73% Phytophthora blight on red pepper, 91% damping-off on cucumber, and 84% Pythium blight on creeping bentgrass, which are similar to those of the CS wettable powder formulation (6.67% CS) containing two times the CS content of MCS 30WP. These observations suggest that the synergistic effect of the MA and CS combination is a sustainable alternative for effective management of destructive oomycete diseases.


Assuntos
Sulfato de Cobre , Phytophthora , Sulfato de Cobre/farmacologia , Maleatos/farmacologia , Phytophthora/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
3.
Microbiol Spectr ; 9(3): e0077921, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34878301

RESUMO

Phenotypic plasticity is a common strategy adopted by fungal pathogens to adapt to diverse host environments. Candida haemulonii is an emerging multidrug-resistant human pathogen that is closely related to Candida auris. Until recently, it was assumed that C. haemulonii is incapable of phenotypic switching or filamentous growth. In this study, we report the identification of three distinct phenotypes in C. haemulonii: white, pink, and filament. The white and pink phenotypes differ in cellular size, colony morphology, and coloration on phloxine B- or CuSO4-containing agar. Switching between the white and pink cell types is heritable and reversible and is referred to as "the primary switching system." The additional switch phenotype, filament, has been identified and exhibits obviously filamentous morphology when grown on glycerol-containing medium. Several unique characteristics of the filamentous phenotype suggest that switching from or to this phenotype poses as a second yeast-filament switching system. The yeast-filament switch is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote filament-yeast transition. We further demonstrated that numerous aspects of the distinct cell types differ in numerous biological aspects, including their high temperature response, specific gene expression, CuSO4 tolerance, secreted aspartyl protease (SAP) activity, and virulence. Therefore, transition among the three phenotypes could enable C. haemulonii to rapidly adapt to, survive, and thrive in certain host niches, thereby contributing to its virulence. IMPORTANCE The capacity to switch between distinct cell types, known as phenotypic switching, is a common strategy adopted by Candida species to adapt to diverse environments. Despite considerable studies on phenotypic plasticity of various Candida species, Candida haemulonii is considered to be incapable of phenotypic switching or filamentous growth. Here, we report and describe filamentation and three distinct phenotypes (white, pink, and filament) in C. haemulonii. The three cell types differ in cellular and colony appearance, gene expression profiles, CuSO4 tolerance, and virulence. C. haemulonii cells switch heritably and reversibly between white and pink cell types, which is referred to as the "primary switching system." Switching between pink and filamentous phenotypes is nonheritable and temperature-dependent, representing a second switching system. As in other Candida species, switching among distinct morphological types may provide C. haemulonii with phenotypic plasticity for rapid responses to the changing host environment, and may contribute to its virulence.


Assuntos
Adaptação Fisiológica/fisiologia , Variação Biológica da População/fisiologia , Candida/classificação , Candida/fisiologia , Fenótipo , Ácido Aspártico Proteases/metabolismo , Candida/genética , Candidíase/microbiologia , Sulfato de Cobre/farmacologia , Regulação Fúngica da Expressão Gênica/genética , Temperatura Alta , Humanos
4.
J Zoo Wildl Med ; 52(1): 97-102, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827166

RESUMO

Copper sulfate immersion is common for the prevention and treatment of Cryptocaryon irritans during quarantine of marine teleosts. The National Aquarium in Baltimore has followed a consistent copper sulfate protocol for marine teleost quarantine since 2004. The protocol used copper sulfate pentahydrate as a slow drip to increase copper ions over 3-5 days to a level of 0.18-0.21 mg/L. This level was maintained for 21 days, and then copper ions were rapidly removed with activated carbon filtration and water changes. Quarantine records from 2004-2016 were used to examine mortality of marine teleosts during copper treatment and identify factors that might have influenced mortality. The following records were excluded: brackish and freshwater teleosts (salinity <25 g/L); long-term treatment at subtherapeutic levels (<0.18 mg/L); intentional short courses (<14 days); and use outside of quarantine. Species, system volume, temperature, parasitic outbreaks, concurrent medications, and water quality concerns were evaluated. During this period, 4,835 individual teleosts belonging to 347 different species were treated. From 2004 to 2016, mortality during copper treatment was 4.1% (199/4,835 individuals) and was higher when treatment was started during the first week of quarantine (7.7%, 68/884) rather than later (3.3%, 131/3,951 individuals). Of the mortalities, 24.1% (48/199) occurred during the initial subtherapeutic period, and 75.9% (151/199) occurred during the therapeutic period. No mortalities occurred in 75.5% (262/347) of species during copper treatment. When using a similar methodology, copper sulfate is a safe immersion for quarantine of marine teleosts. Mortalities during copper treatment can be reduced by increasing copper ion levels to therapeutic ranges more slowly (e.g., over 7 days) and starting copper treatment after the first week of quarantine.


Assuntos
Antídotos/farmacologia , Antiparasitários/farmacologia , Sulfato de Cobre/farmacologia , Doenças dos Peixes/parasitologia , Animais , Animais de Zoológico , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Antiparasitários/administração & dosagem , Baltimore , Sulfato de Cobre/administração & dosagem , Sulfato de Cobre/efeitos adversos , Doenças dos Peixes/prevenção & controle , Peixes , Quarentena
5.
Int J Biol Macromol ; 183: 23-34, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33862078

RESUMO

In the present work, copper/chitosan nanocomposites (Cu/CS) were prepared in an aqueous solution in the presence of CS as stabilizer and CuSO4·5H2O precursor. The Cu/CS NPs formation was proved through transmission electron microscopy (TEM), Dynamic light scattering (DLS), Fourier Transform infrared (FT-IR) spectroscopy and XRD diffraction. Cotton and cotton/polyester fabrics were gamma-radiation grafted by padding to pickup of 100%, in nanocomposites based on Cu/CS NPs loaded in polymer blends of poly(vinyl alcohol) (PVA) and plasticized starch (PLST). The grafted fabrics were characterized in terms of tensile mechanical, crease recovery and water absorption properties. The results showed that cotton fabrics displayed higher water absorption (%) than cotton/polyester fabrics for all PVA/PLST compositions and water absorption was found to decrease with increasing the ratio of PVA in the PVA/PLST blends. Cotton/polyester fabrics displays crease recovery angle (CRA) value of 147.6 upon treated with PVA/PLST (80/20%) and gamma irradiated to 30 kGy compared to CRA value of 125.0 for cotton fabrics treated under the same conditions. For cotton fabrics, the tensile strength was largely depends on the irradiation dose, in which the tensile strength of the treated fabric with the different formulations is higher than the untreated fabric. The antimicrobial activity of the fabrics against gram-positive bacteria (Staphylococcus aurous) and gram-negative bacteria (Escherichia coli) was investigated. In case of gram-positive bacteria cotton fabric showed the highest impact, for both 50/50 and 20/80 PVA/PLST of 14 and 14.5 mm inhibition zone, whilst, cotton/polyester fabric recorded 6 and 5 mm inhibition zone against gram-negative bacteria for 50/50 and 20/80 PVA/PLST, respectively.


Assuntos
Antibacterianos/farmacologia , Quitosana/química , Sulfato de Cobre/farmacologia , Fibra de Algodão , Raios gama , Nanocompostos , Poliésteres/química , Absorção Fisico-Química , Antibacterianos/química , Antibacterianos/efeitos da radiação , Quitosana/efeitos da radiação , Sulfato de Cobre/química , Sulfato de Cobre/efeitos da radiação , Fibra de Algodão/microbiologia , Fibra de Algodão/efeitos da radiação , Composição de Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Poliésteres/efeitos da radiação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Propriedades de Superfície , Resistência à Tração , Água/química
6.
Int J Mol Sci ; 22(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672733

RESUMO

Sigma factor C (SigC) contributes to Mycobacterium tuberculosis virulence in various animal models, but the stress response coordinated by this transcription factor was undefined. The results presented here indicate that SigC prevents copper starvation. Whole genome expression studies demonstrate short-term (4-h) induction of sigC, controlled from a tetracycline-inducible promoter, upregulates ctpB and genes in the nonribosomal peptide synthase (nrp) operon. These genes are expressed at higher levels after 48-h sigC induction, but also elevated are genes encoding copper-responsive regulator RicR and RicR-regulated copper toxicity response operon genes rv0846-rv0850, suggesting prolonged sigC induction results in excessive copper uptake. No growth and global transcriptional differences are observed between a sigC null mutant relative to its parent strain in 7H9 medium. In a copper-deficient medium, however, growth of the sigC deletion strain lags the parent, and 40 genes (including those in the nrp operon) are differentially expressed. Copper supplementation reverses the growth defect and silences most transcriptional differences. Together, these data support SigC as a transcriptional regulator of copper acquisition when the metal is scarce. Attenuation of sigC mutants in severe combined immunodeficient mice is consistent with an inability to overcome innate host defenses that sequester copper ions to deprive invading microbes of this essential micronutrient.


Assuntos
Cobre/farmacologia , Imunidade/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Fator sigma/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Transporte Biológico/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Camundongos SCID , Viabilidade Microbiana/efeitos dos fármacos , Mutação/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Fenótipo , Transcrição Genética/efeitos dos fármacos , Virulência/efeitos dos fármacos , Virulência/genética
7.
J Anim Physiol Anim Nutr (Berl) ; 105(5): 849-860, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33764632

RESUMO

Two trials were carried out to study the effects of copper sulphate (CuSO4 ) on detoxifying glucosinolates (GLS) in rapeseed cake (RSC) and compare the effects of feeding CuSO4 -treated and untreated RSC on nutrient digestion and nitrogen (N) metabolism in steers. In Trial 1, different concentrations of CuSO4 solution (1.6 vs. 3.2 g CuSO4 ·5H2 O L-1 ), soaking temperatures (25 vs. 60°C) and drying methods (air drying at 60°C vs. freeze drying) were allocated in a 2 × 2 × 2 factorial arrangement in vitro. In Trial 2, six steers and dietary inclusions of untreated RSC (control), CuSO4 -treated RSC and CuSO4 -added RSC were assigned in a replicated 3 × 3 Latin square design. CuSO4 treatment in vitro decreased the contents of GLS and thiocyanate (TC) in RSC (p < 0.001). The total amount of GLS and TC decreased by 62.7-68.5% for all treatments. The animal trial showed that CuSO4 -treated RSC inclusion decreased ruminal concentration of valerate (p < 0.01), whereas it did not affect ruminal pH, ammonia N and total volatile fatty acids. Compared with the control, feeding CuSO4 -treated or CuSO4 -added RSC had no effect on plasma concentrations of triiodothyronine and thyroxine, N excretion and N retention. CuSO4 -treated RSC tended to increase neutral detergent fibre digestibility (p = 0.072) and urinary excretion of urea (p = 0.056). Urinary excretion of purine derivatives (p = 0.076) and rumen microbial N supply (p = 0.084) tended to decrease when feeding CuSO4 -treated RSC versus control. TC was found to be the only metabolite of GLS in rumen fluid, plasma and urine. It was feasible to detoxify GLS in RSC using low CuSO4 at room temperature. However, feeding CuSO4 -treated or CuSO4 -added RSC had minor effects on rumen fermentation, nutrient digestion and N metabolism in steers. CuSO4 treatment on RSC for feeding steers seems to be unnecessary.


Assuntos
Brassica napus , Rúmen , Ração Animal/análise , Animais , Bovinos , Sulfato de Cobre/farmacologia , Dieta/veterinária , Digestão , Fermentação , Glucosinolatos/metabolismo , Glucosinolatos/farmacologia , Masculino , Nitrogênio/metabolismo , Nutrientes , Rúmen/metabolismo
8.
Sci Rep ; 11(1): 5485, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750827

RESUMO

Even though the use of antibiotics for food-producing animals may contribute to the emergence of antimicrobial resistance, antibiotics are still used as growth promoters. Due to consumer and regulatory pressures, the use of alternatives to antibiotics as growth promoters is increasing, thus more information is needed on their capability to disseminate antimicrobial resistance compared to antibiotics. We investigated the impacts of carbadox (antibiotic), copper sulfate and zinc oxide (metals) and mushroom powder (natural product) on the pig fecal resistome and microbiome. Antibiotic resistance gene (ARG) and mobile genetic element (MGE) abundances were measured using a high-throughput qPCR array with 382 primer pairs. Bacterial community composition was determined by 16S rRNA gene sequencing. More ARGs co-occurred with MGEs in the growth promoter group samples than in the control group samples. Community composition could not be linked to resistome in the growth promoter group samples, indicating a potential decoupling of ARGs and phylogeny. Additionally, machine-learning methods aided in defining the community and resistome differences in response to treatments. Since increased ARG mobility potential was the primary response to the dietary additives used in this study, we suggest that ARG mobility should be considered when designing antimicrobial use policies and antimicrobial resistance surveillances.


Assuntos
Antibacterianos/farmacologia , Carbadox/farmacologia , Sulfato de Cobre/farmacologia , Suínos/crescimento & desenvolvimento , Óxido de Zinco/farmacologia , Agaricales/química , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Resistência Microbiana a Medicamentos , Feminino , Genes Bacterianos/efeitos dos fármacos , Masculino , Microbiota/efeitos dos fármacos
9.
J Trace Elem Med Biol ; 65: 126721, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33508548

RESUMO

BACKGROUND: Excess copper (Cu) is an oxidative stress factor which associates with a variety of diseases. The aim of this study was to evaluate the effect of Cu in primary chicken embryo hepatocytes (CEHs). METHODS: CEHs were isolated from 13 days old chicken embryos and followed by different concentration Cu (0, 10, 100, 200 µM) and/or ALC treatment (0.3 mg/mL) for 12 or 24 h. The effects of Cu exposure in CEHs were determined by detecting reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP), and ATP levels. The expression of mitochondrial dynamics-related genes and proteins were also detected. RESULTS: Results showed that Cu treatment (100 or 200 µM) significantly decreased CEHs viability, MMP and ATP levels, increased ROS and MDA levels in 12 or 24 h. The up-regulated mitochondrial fission genes and protein in 100 and 200 µM Cu groups suggested Cu promoted mitochondrial division but not fusion. However, the co-treatment of ALC and Cu alleviated those changes compared with the 100 or 200 µM Cu groups. CONCLUSION: In conclusion, we speculated that Cu increased the oxidative stress and induced mitochondria dysfunction via disturbing mitochondrial dynamic balance in CEHs, and this process was not completely reversible.


Assuntos
Sulfato de Cobre/farmacologia , Hepatócitos/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Galinhas , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Malondialdeído/análise , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
10.
J Trace Elem Med Biol ; 65: 126711, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33486291

RESUMO

BACKGROUND: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer's disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. METHODS: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. RESULTS: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 µM) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. CONCLUSION: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.


Assuntos
Astrócitos/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Astrócitos/metabolismo , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Sulfato de Cobre/metabolismo , Relação Dose-Resposta a Droga , Humanos , Estresse Oxidativo/efeitos dos fármacos
11.
Neurotoxicology ; 82: 18-25, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33127410

RESUMO

1-Methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP+ include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein. Another important mechanism of damage, is MPP + interference with mitochondrial respiration. Both, oxidative stress and inhibition of mitochondrial respiration may trigger apoptosis in the neurons after MPP+. The aim of the present study was to characterize the time-course of apoptosis induced by MPP+ to determine if copper sulfate pretreatment is able to prevent the activation of caspases and decreased the neuronal apoptosis. MPP+ was microinjected into rat striatum using a stereotactic frame. The results showed increased activities of caspases 8, 9 and 3, between 72-120 hours after administration of MPP+, both in striatum and midbrain. After this study, we tested the effect of CuSO4 on MPP+ neurotoxicity, showing a diminution of the apoptotic damage induced by MPP+, decreased levels of enzymatic activity of caspases: 8 (-34 and -25 %), 9 (-25 and -42 %) and 3 (-40 and -29 %) in striatum and midbrain, respectively. Finally, we performed an immunohistochemical analysis, evidencing a decreased number of apoptotic cells in the groups pretreated with copper sulfate pretreatment compared to the control group. With these findings, it is concluded that pretreatment with copper sulfate may be a good alternative to prevent MPP+-induced apoptosis.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Apoptose/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Corpo Estriado/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , 1-Metil-4-fenilpiridínio/antagonistas & inibidores , Animais , Anexina A5/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Wistar
12.
Poult Sci ; 99(12): 6964-6973, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33248612

RESUMO

This study was designed to compare the effects of nutritional and growth-promoting levels of copper hydroxychloride (CH) with copper sulfate (CuSO4) on growth, carcass characteristics, tibia traits and mineral concentration in broilers fed a conventional wheat-soybean meal-based diet. Day-old Ross 308 male chicks (n = 864) were randomly assigned into 8 dietary treatments with 6 replicates of 18 chicks per treatment. The dietary treatments included a basal diet containing no supplemental copper (Cu) serving as the negative control (NC); basal diet supplemented with 15 or 200 mg/kg Cu as CuSO4; basal diet supplemented with either 15, 50, 100, 150, or 200 mg/kg Cu from CH. Diets were fed over the starter (day 1-14) and grower (day 14-35) phases. Birds in the NC group gained the same body weight and had similar feed conversion ratio (FCR) to birds receiving 15 mg/kg Cu as CuSO4, but birds receiving 15 mg/kg Cu as CH had a lower FCR than the NC birds (day 0-35; P < 0.05). Birds fed 200 mg/kg Cu as CH gained more weight (77 g/bird) and had a lower FCR (3.2 point) compared with those fed 200 mg/kg Cu as CuSO4 (P < 0.01). Based on broken-line regression models, the optimum inclusion level of Cu as CH in the diet for optimal body weight gain and FCR were estimated to be 109.5 and 72.3 mg/kg, respectively (P < 0.001). Carcass characteristics were not affected by dietary Cu sources or levels (P > 0.05). The highest and lowest tibia ash content were observed in birds fed diet with 150 mg/kg Cu as CH and 200 mg/kg Cu as CuSO4, respectively (P < 0.05). Supplementation with 200 mg/kg Cu as CH resulted in higher duodenal mucosa Cu content compared with the diet containing 200 mg/kg Cu as CuSO4 (P < 0.001). In conclusion, supplementation of Cu from CH was more efficacious than CuSO4 in promoting growth performance, both at nutritional and pharmacological levels.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Galinhas , Sulfato de Cobre , Suplementos Nutricionais , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/crescimento & desenvolvimento , Sulfato de Cobre/farmacologia , Dieta/veterinária , Mucosa Intestinal/efeitos dos fármacos , Masculino , Distribuição Aleatória
13.
Bull Exp Biol Med ; 169(6): 791-794, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33098514

RESUMO

Chloride current (IGly) evoked by the rapid (600 msec) application of glycine on isolated pyramidal neurons of the rat hippocampus was recorded using the patch clamp technique. We studied the effect of individual or combined application of copper ions (Cu2+) and protons (H+) on IGly. It was found that both Cu2+ (10 µM) and H+ (pH 7.0 and 6.0) applied separately caused a fast and reversible effect on IGly that included two components: a decrease in peak amplitude (Ipeak) and a decrease in the desensitization time constant (τdes). During combined application, the effects on Ipeak were additive, which indicates the independence of the mechanisms of these effects. At the same time, the effect of combined application of Cu2+ and H+ on τdes was not additive and sometimes a slowdown of the total desensitization was observed. The latter result suggests that H+ and Cu2+ can play the role of mutual antagonists when they affect the desensitization of GlyR.


Assuntos
Sulfato de Cobre/farmacologia , Glicina/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Prótons , Células Piramidais/efeitos dos fármacos , Receptores de Glicina/metabolismo , Animais , Transporte Biológico , Região CA3 Hipocampal/citologia , Região CA3 Hipocampal/metabolismo , Glicina/metabolismo , Concentração de Íons de Hidrogênio , Potenciais da Membrana/fisiologia , Técnicas de Patch-Clamp , Cultura Primária de Células , Células Piramidais/citologia , Células Piramidais/metabolismo , Ratos , Ratos Wistar
14.
Biomolecules ; 10(10)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081293

RESUMO

Cochlear hair cells in human beings cannot regenerate after loss; however, those in fish and other lower species can. Recently, the role of inflammation in hair cell regeneration has been attracting the attention of scientists. In the present study, we investigated how suppression of inflammatory factors affects hair cell regeneration and the functional recovery of regenerated hair cells in zebrafish. We killed hair cells in the lateral line of zebrafish larvae with CuSO4 to induce an inflammatory response and coapplied BRS-28, an anti-inflammatory agent to suppress the inflammation. The recovery of the hair cell number and rheotaxis was slower when CuSO4 and BRS-28 were coapplied than when CuSO4 was applied alone. The recovery of hair cell count lagged behind that of the calcium imaging signal during the regeneration. The calcium imaging signal in the neuromasts in the inflammation-inhibited group was weaker than that in the noninflammation-inhibited group at the early stage of regeneration, although it returned to normal at the late stage. Our study demonstrates that suppressing inflammation by BRS-28 delays hair cell regeneration and functional recovery when hair cells are damaged. We suspect that BRS-28 inhibits pro-inflammatory factors and thereby reduces the migration of macrophages to delay the regeneration of hair cells.


Assuntos
Células Ciliadas Vestibulares/citologia , Inflamação/genética , Regeneração/genética , Peixe-Zebra/genética , Animais , Morte Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sulfato de Cobre/farmacologia , Células Ciliadas Vestibulares/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Larva/genética , Larva/crescimento & desenvolvimento , Sistema da Linha Lateral/crescimento & desenvolvimento , Sistema da Linha Lateral/patologia , Macrófagos , Peixe-Zebra/crescimento & desenvolvimento
15.
Virulence ; 11(1): 1108-1121, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32862758

RESUMO

Cu is an essential trace element for cell growth and proliferation. However, excess of Cu accumulation leads to cellular toxicity. Thus, precise and tight regulation of Cu homeostasis processes, including transport, delivery, storage, detoxification, and efflux machineries, is required. Moreover, the maintenance of Cu homeostasis is critical for the survival and virulence of fungal pathogens. Cu homeostasis has been extensively studied in mammals, bacteria, and yeast, but it has not yet been well documented in filamentous fungi. In the present work, we investigated Cu tolerance in the filamentous fungus Fusarium oxysporum by analysing the Cu transporter coding gene crpF, previously studied in Aspergillus fumigatus. The expression studies demonstrated that crpF is upregulated in the presence of Cu and its deletion leads to severe sensitivity to low levels of CuSO4 in F. oxysporum. Targeted deletion of crpF did not significantly alter the resistance of the fungus to macrophage killing, nor its pathogenic behaviour on the tomato plants. However, the targeted deletion mutant ΔcrpF showed increased virulence in a murine model of systemic infection compared to wild-type strain (wt).


Assuntos
Proteínas de Transporte de Cobre/genética , Cobre/toxicidade , Proteínas Fúngicas/genética , Fusarium/química , Fusarium/efeitos dos fármacos , Animais , Linhagem Celular , Sulfato de Cobre/farmacologia , Proteínas de Transporte de Cobre/metabolismo , Proteínas Fúngicas/metabolismo , Fusarium/patogenicidade , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Homeostase , Lycopersicon esculentum/microbiologia , Macrófagos/microbiologia , Masculino , Camundongos , Doenças das Plantas/microbiologia , Virulência
16.
PLoS One ; 15(7): e0235929, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645104

RESUMO

Combinations of three or more drugs are routinely used in various medical fields such as clinical oncology and infectious diseases to prevent resistance or to achieve synergistic therapeutic benefits. The very large number of possible high-order drug combinations presents a formidable challenge for discovering synergistic drug combinations. Here, we establish a guided screen to discover synergistic three-drug combinations. Using traditional checkerboard and recently developed diagonal methods, we experimentally measured all pairwise interactions among eight compounds in Erwinia amylovora, the causative agent of fire blight. Showing that synergy measurements of these two methods agree, we predicted synergy/antagonism scores for all possible three-drug combinations by averaging the synergy scores of pairwise interactions. We validated these predictions by experimentally measuring 35 three-drug interactions. Therefore, our guided screen for discovering three-drug synergies is (i) experimental screen of all pairwise interactions using diagonal method, (ii) averaging pairwise scores among components to predict three-drug interaction scores, (iii) experimental testing of top predictions. In our study, this strategy resulted in a five-fold reduction in screen size to find the most synergistic three-drug combinations.


Assuntos
Antibacterianos/química , Sinergismo Farmacológico , Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Sulfato de Cobre/química , Sulfato de Cobre/farmacologia , Interações Medicamentosas , Erwinia amylovora/efeitos dos fármacos , Erwinia amylovora/crescimento & desenvolvimento , Gentamicinas/química , Testes de Sensibilidade Microbiana
17.
ACS Synth Biol ; 9(8): 2208-2213, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32584553

RESUMO

Promoters are critical tools to precisely control gene expression for both synthetic biology and metabolic engineering. Although Yarrowia lipolytica has demonstrated many industrially relevant advantages, promoter discovery efforts on this non-conventional yeast are limited due to the challenge in finding suitable inducible and repressible promoters. Six copper-inducible promoters and five repressible promoters were isolated in this work. Especially, Cu2+-repressible promoters showed relatively high activity under non-repressing conditions compared with a constitutive promoter, but the strength could be almost fully repressed by a supplement of a low content of Cu2+. The six Cu2+-inducible promoters were engineered to improve their dynamic regulation range with a tandem upstream activation sequence. An engineered promoter was successfully used to construct a more productive pathway for production of a novel bioproduct, wax ester, than that used for both Cu2+-inducible promoter and constitutive promoter. This study provides effective tools applicable to fine-tune the gene expression in this microbial host.


Assuntos
Expressão Gênica , Yarrowia/metabolismo , Sequência de Aminoácidos , Sulfato de Cobre/farmacologia , Proteínas de Transporte de Cobre/genética , Proteínas de Transporte de Cobre/metabolismo , Expressão Gênica/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Engenharia Metabólica , Metalotioneína/química , Metalotioneína/genética , Regiões Promotoras Genéticas , Alinhamento de Sequência , Yarrowia/genética
18.
Chemosphere ; 256: 126974, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32470726

RESUMO

Copper is a widespread heavy metal in environment and has toxic effects when exposed. However, study of copper-induced male reproductive toxicity is still insufficient to report, and the underlying mechanisms are unknown. Keeping in view, RNA-Seq and metabolomic were performed to identify metabolic pathways that were distressed in mouse spermatogonia with the effect of copper sulfate, and the integrated analysis of the mechanism of copper administered GC-1 cells from metabolomic and transcriptomic data. Our results demonstrated that many genes and metabolites were regulated in the copper sulfate-treated cells. The differential metabolites analysis showed that 49 and 127 metabolites were significantly different in ESI+ and ESI- mode, respectively. Meanwhile, a total of 2813 genes were up-regulated and 2488 genes were down-regulated in the treatment groups compared to those in the control groups. Interestingly, ophthalmic acid and gamma glutamylleucine were markedly increased by copper treatment in two modes. By integrating with transcriptomic and metabolomic data, we revealed that 37 and 22 most related pathways were over-enriched in ESI+ and ESI- mode, respectively. Whereas, amino acid biosynthesis and metabolism play essential role in the potential relationship between DEGs and metabolites, which suggests that amino acid biosynthesis and metabolism may be the major metabolic pathways disturbed by copper in GC-1 cells. This study provides important clues and evidence for understanding the mechanisms responsible for copper-induced male spermatogenesis toxicity, and useful biomarkers indicative of copper exposure could be discovered from present study.


Assuntos
Cobre/toxicidade , Poluentes Ambientais/toxicidade , Espermatogônias/efeitos dos fármacos , Animais , Sulfato de Cobre/farmacologia , Regulação para Baixo/efeitos dos fármacos , Masculino , Redes e Vias Metabólicas , Metabolômica , Camundongos , Transcriptoma/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
19.
Chembiochem ; 21(18): 2620-2627, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32346945

RESUMO

Peroxidase-mimicking nanozymes that can generate toxic hydroxyl radicals (. OH) hold great promise as antibacterial alternatives. However, most of them display optimal performance under strongly acidic conditions (pH 3-4), and are thus not feasible for many medical uses, including burn infections with a wound pH close to neutral. Herein, we report a copper-based nanozyme (CuCo2 S4 ) that exhibits intrinsic peroxidase-like activity and can convert H2 O2 into . OH at neutral pH. In particular, bimetallic CuCo2 S4 nanoparticles (NPs) exhibited enhanced peroxidase-like activity and antibacterial capacity, superior to that of the corresponding monometallic CuS and CoS NPs. The CuCo2 S4 nanozymes possessed excellent ability to kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, this CuCo2 S4 nanozymes could effectively disrupt MRSA biofilms in vitro and accelerate MRSA-infected burn healing in vivo. This work provides a new peroxidase mimic to combat bacteria in neutral pH milieu and this CuCo2 S4 nanozyme could be a promising antibacterial agent for the treatment of burn infections.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Cobalto/farmacologia , Sulfato de Cobre/farmacologia , Nanopartículas/química , Peroxidase/metabolismo , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Queimaduras/metabolismo , Queimaduras/microbiologia , Cobalto/química , Sulfato de Cobre/química , Concentração de Íons de Hidrogênio , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Peroxidase/química , Propriedades de Superfície
20.
FEBS J ; 287(17): 3827-3840, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153092

RESUMO

The scsABCD (suppressor of copper sensitivity) locus of Salmonella encodes four proteins that resemble the disulfide folding machinery of other bacteria. Previous work has shown that Salmonella encounters toxic levels of copper during infection and the Scs system provides protection against this copper-mediated toxicity. The current work reports that expression of the soluble periplasmic protein StScsC is induced by copper and that intramacrophage survival in the presence of copper is diminished by the loss of StScsC. Using a combination of genetic and proteomic approaches, the abundance of various cysteine-containing periplasmic proteins was found to be elevated by StScsC in the Salmonella periplasm, implicating StScsC in the disulfide folding of superoxide dismutases and proteins involved in amino acid sensing and import. Co-purification and mass spectrometry approaches confirmed that the arginine-sensing periplasmic protein ArtI associates with StScsC via a disulfide interaction, and purified ArtI was shown to alter the thiol redox state of purified StScsC. This work reports the first demonstration of a redox partner for the Scs system of Salmonella and provides insights into how this bacterial pathogen responds to copper stress during infection.


Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Proteínas de Bactérias/fisiologia , Sulfato de Cobre/farmacologia , Macrófagos/microbiologia , Proteínas Periplásmicas/fisiologia , Salmonella typhimurium/fisiologia , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Sequência de Aminoácidos , Animais , Arginina/metabolismo , Carga Bacteriana , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Transporte Biológico , Dissulfetos/metabolismo , Escherichia coli/metabolismo , Genes Bacterianos , Bactérias Gram-Negativas/genética , Camundongos , Modelos Moleculares , Oxirredução , Proteínas Periplásmicas/química , Proteínas Periplásmicas/genética , Conformação Proteica , Dobramento de Proteína , Mapeamento de Interação de Proteínas , Células RAW 264.7 , Proteínas Recombinantes/metabolismo , Salmonelose Animal/microbiologia , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
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