RESUMO
The knowledge of biological trace minerals and phytase requirements for modern broiler genotypes is not established and the pressure to reduce their usage in animal feeding due to environmental issues is increasing. Here, the alkaline phosphatase (ALP) and tartarate-resistant acid phosphatase (TRAP) of the tibia and serum of broilers fed with diets containing various levels of phytase and reduced levels of zinc, manganese, and copper was evaluated. The experiment was performed using 1,200 male Cobb broilers raised according to standard commercial husbandry techniques. Data were analyzed as a 4×3 factorial arrangement with four concentrations of zinc (0.34, 0.49, 0.64, and 0.79 ppm), manganese (0.18, 0.43, 0.68, and 0.93 ppm), or copper (0.09, 0.12, 0.15, and 0.18 ppm) and three concentrations of phytase (0, 500, and 1,000 FTU/kg) for age periods of 1-21 and 36-42 days. While the dietary supplementation with copper did not induce a significant effect in bone tissue biochemical markers, serum TRAP activity of 42-day old broilers increased with higher copper levels. Increasing dietary zinc levels linearly increased ALP activity in tibia growth, suggesting that zinc is essential for longitudinal bone growth. Phytase significantly promoted the increase of TRAP and ALP activities, suggesting that manganese increased growth plate activity, accelerated calcification, and remodeled the newly formed tissue into trabecular bone. Although not every enzymatic activity was affected by the treatments, the phytase use, along with trace minerals, improved the animal response to the rapid growth required nowadays and provided the nutrients for adequate bone metabolism.(AU)
Assuntos
Animais , Galinhas/fisiologia , Monoéster Fosfórico Hidrolases/síntese química , Zinco/efeitos adversos , Cobre/efeitos adversos , Manganês/efeitos adversosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Harpalyce brasiliana Benth (Leguminosae) is a shrub endemic to Brazil, popularly known as "snake's root." This species is used in folk medicine for the treatment of inflammation and snakebites. However, up to now there is no scientific research to justify its popular use. The study aimed to characterize the phytochemical profile of the hydroethanol extract from the roots of H. brasiliana (Hb), to evaluate its antioxidant and anti-inflammatory potential, as well as to investigate its cytotoxicity and acute toxicity. MATERIALS AND METHODS: The extract was obtained by maceration method using a solution of ethanol:water (70: 30, v/v). The phytochemical profile was obtained by liquid chromatography coupled to mass spectrometry. The cytotoxicity of extract (31-2000 µg/mL) was evaluated in vitro, by the 3-methyl-[4-5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method using murine macrophage and fibroblast cell lines (RAW 247.6 and 3T3, respectively) and by the hemolytic assay. For the in vivo acute toxicity, the extract (2000 mg/kg) was administered and after 14 days the weight (body and organs) and hematological and biochemical parameters were analyzed. Chemical free radical scavenging effect of the extract (125-2000 µg/mL) was investigated through diphenylpicryl hydrazine reduction, total antioxidant capacity, reducing power, hydroxyl radical scavenging, and iron and copper chelating assays. In vitro anti-inflammatory effect of the extract (125, 500, and 2000 µg/mL) was demonstrated through of nitric oxide (NO) analyzed in lipopolysaccharides stimulated RAW 264.7 cells. In vivo anti-inflammatory activities were evaluated in carrageenan-induced paw edema and zymosan-air-pouch models, with gavage administration (post-treatment) of extract at 100, 200, and 400 mg/kg. For the first animal model, the anti-edematogenic activity and myeloperoxidase (MPO) levels were investigated, while in the zymosan-air-pouch model the leukocyte number, MPO, total protein and pro-inflammatory cytokine (IL-1ß, IL-6, and TNF-α) levels were quantified. In addition, the oxidative parameters such as malondialdehyde (MDA) and reduced glutathione (GSH) were determined. RESULTS: The phytochemical profile revealed the presence of 20 compounds, mainly prenylated and geranylated pterocarpans. The extract demonstrated no cytotoxicity in erythrocytes, macrophages and fibroblasts cells at the tested concentrations, as well as no sign of toxicity and mortality or significant alterations on the hematological and biochemical parameters in the acute toxicity model. The extract was also able to neutralize chemical free radicals, with copper and iron chelating effect. For the NO dosage, the extract evidenced the reduction of expression of NO after the administration of the extract (500 and 2000 µg/mL). The edematogenic model revealed a decrease in paw edema and MPO level, while the zymosan-air-pouch model evidenced a reduction of leukocyte number (especially of polymorphornuclears), MPO production, and total protein and cytokine levels, and demonstrated the antioxidant effect through a decrease in MDA and increase in GSH parameters. CONCLUSION: This approach demonstrates for the first time that Hb is not cytotoxic, has low acute toxicity, and possesses antioxidant and anti-inflammatory properties in preclinical analyses, corroborating its popular use.
Assuntos
Antioxidantes , Fabaceae , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Antioxidantes/toxicidade , Carragenina , Cobre/efeitos adversos , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Camundongos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , ZimosanRESUMO
The aim of this study was to evaluate, through nonlinear regression models, the initial development of soybean (Glycine max L. Merr. cv. BRS 257) in soil supplemented with different copper levels. The experiment was performed in a greenhouse under natural light and temperature conditions. The seeds were sowed in soil containing different copper levels (11.20, 32.28, 52.31, 64.51, 79.42, 117.70, 133.53, 144.32, or 164.00 mg kg- 1). Germination percentage was not affected by the increase of copper content in the soil, but there was a delay in the germination process. There was no influence of copper levels on the seedling emergence speed index until 98.42 mg kg- 1; however, higher copper amounts reduced this parameter. Low copper concentrations increased plant development, but higher concentrations compromised mainly root growth. Overall, these results suggest that copper supplementation in the soil exerted dose-dependent dual effects on soybean seedlings.
Assuntos
Cobre/efeitos adversos , Germinação/efeitos dos fármacos , Glycine max/efeitos dos fármacos , Poluentes do Solo/efeitos adversos , Relação Dose-Resposta a Droga , Dinâmica não Linear , Análise de Regressão , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Solo/química , Glycine max/crescimento & desenvolvimentoRESUMO
BACKGROUND: The marine alga Ulva compressa is the dominant species in copper-polluted coastal areas in northern Chile. It has been shown that the alga tolerates micromolar concentrations of copper and accumulates copper at the intracellular level. Transcriptomic analyses were performed using total RNA of the alga cultivated with 10 µ M copper for 0, 1, 3 and 5 days using RNA-seq in order to identify processes involved in copper tolerance. RESULTS: The levels of transcripts encoding proteins belonging to Light Harvesting Complex II (LHCII), photosystem II (PSII), cytochrome b6f, PSI, LHCI, ATP synthase and proteins involved in repair of PSII and protection of PSI were increased in the alga cultivated with copper. In addition, the level of transcripts encoding proteins of mitochondrial electron transport chain, ATP synthase, and enzymes involved in C, N and S assimilation were also enhanced. The higher percentages of increase in the level of transcripts were mainly observed at days 3 and 5. In contrast, transcripts involved protein synthesis and degradation, signal transduction, and replication and DNA repair, were decreased. In addition, net photosynthesis and respiration increased in the alga cultivated with copper, mainly at days 1 to 3. Furthermore, the activities of enzymes involved in C, N and S assimilation, rubisco, glutamine synthase and cysteine synthase, respectively, were also increased, mainly at days 1 and 3. CONCLUSIONS: The marine alga U. compressa tolerates copper excess through a concomitant increase in expression of proteins involved in photosynthesis, respiration, and C, N and S assimilation, which represents an exceptional mechanism of copper tolerance.
Assuntos
Cobre/efeitos adversos , Fotossíntese/efeitos dos fármacos , Ulva/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Proteínas de Algas/análise , Carbono/metabolismo , Perfilação da Expressão Gênica , Nitrogênio/metabolismo , Oxigênio/metabolismo , Enxofre/metabolismo , Ulva/metabolismo , Ulva/fisiologiaRESUMO
Copper is a micronutrient for living organisms, but at high concentrations it may cause several deleterious effects. The objective of this study was to evaluate the behavior of agricultural crops to different concentrations of Cu in the soil. The species Triticum aestivum (wheat), Zea mays (maize), Oryza sativa (rice), Phaseolus vulgaris (dry bean), Glycine max (soybean), and Raphanus sativus (radish) were cultivated in the soils Typic Hapludox (TyHpx) and Rhodic Acrudox (RhAcx). The experiment was carried out in a greenhouse and the soils were set in pots in a completely randomized design, with four replicates per treatment adding the following Cu concentrations (as Cu-nitrate): 0, 75, 150, 300, 600, 800, 1000, 1200 mg kg-¹ dry soil. Measurements of biological variables, such as shoot dry weight (SDW), plant height, stem diameter, and number of leaves were carried out, in addition to determining Cu content in the SDW. At the TyHpx, a decreasing order of tolerance to Cu phytotoxicity was: dry bean, maize, soybean, wheat, radish, and rice. However, at the RhAcx, the decreasing order was: maize, soybean, radish, wheat, dry bean, and rice. The species that revealed the highest sensitivity to high Cu concentrations in soil was rice and that with the lowest sensitivity was maize.(AU)
O cobre é um micronutriente para organismos vivos, mas em altas concentrações pode causar vários efeitos deletérios. O objetivo deste estudo foi avaliar o comportamento de culturas agrícolas em diferentes concentrações de Cu no solo. As espécies Triticum aestivum (trigo), Zea mays (milho), Oryza sativa (arroz), Phaseolus vulgaris (feijão), Glycine max (soja) e Raphanus sativus (rabanete) foram cultivadas nos solos Latossolo Vermelho Amarelo distrófico típico (LVAd) e Latossolo Vermelho distroférrico típico (LVdf). O experimento foi realizado em casa de vegetação e os solos foram colocados em vasos, em delineamento inteiramente casualizado, com quatro repetições por tratamento, adicionando às seguintes concentrações de Cu (como nitrato de Cu): 0, 75, 150, 300, 600, 800, 1000, 1200 mg kg-¹ de solo seco. Foram realizadas medidas das variáveis biológicas matéria seca da parte aérea (MSPA), altura da planta, diâmetro do caule e número de folhas, além disso foi determinado o teor de Cu na MSPA. No LVAd, a ordem decrescente de tolerância à fitotoxicidade do Cu foi: feijão, milho, soja, trigo, rabanete e arroz. No entanto, no LVdf, a ordem decrescente foi: milho, soja, rabanete, trigo, feijão e arroz. A espécie que revelou maior sensibilidade às altas concentrações de Cu no solo foi o arroz e a que apresentou menor sensibilidade foi o milho.(AU)
Assuntos
Cobre/efeitos adversos , Cobre/toxicidade , Solo/química , Grão ComestívelRESUMO
Copper is a micronutrient for living organisms, but at high concentrations it may cause several deleterious effects. The objective of this study was to evaluate the behavior of agricultural crops to different concentrations of Cu in the soil. The species Triticum aestivum (wheat), Zea mays (maize), Oryza sativa (rice), Phaseolus vulgaris (dry bean), Glycine max (soybean), and Raphanus sativus (radish) were cultivated in the soils Typic Hapludox (TyHpx) and Rhodic Acrudox (RhAcx). The experiment was carried out in a greenhouse and the soils were set in pots in a completely randomized design, with four replicates per treatment adding the following Cu concentrations (as Cu-nitrate): 0, 75, 150, 300, 600, 800, 1000, 1200 mg kg-¹ dry soil. Measurements of biological variables, such as shoot dry weight (SDW), plant height, stem diameter, and number of leaves were carried out, in addition to determining Cu content in the SDW. At the TyHpx, a decreasing order of tolerance to Cu phytotoxicity was: dry bean, maize, soybean, wheat, radish, and rice. However, at the RhAcx, the decreasing order was: maize, soybean, radish, wheat, dry bean, and rice. The species that revealed the highest sensitivity to high Cu concentrations in soil was rice and that with the lowest sensitivity was maize.
O cobre é um micronutriente para organismos vivos, mas em altas concentrações pode causar vários efeitos deletérios. O objetivo deste estudo foi avaliar o comportamento de culturas agrícolas em diferentes concentrações de Cu no solo. As espécies Triticum aestivum (trigo), Zea mays (milho), Oryza sativa (arroz), Phaseolus vulgaris (feijão), Glycine max (soja) e Raphanus sativus (rabanete) foram cultivadas nos solos Latossolo Vermelho Amarelo distrófico típico (LVAd) e Latossolo Vermelho distroférrico típico (LVdf). O experimento foi realizado em casa de vegetação e os solos foram colocados em vasos, em delineamento inteiramente casualizado, com quatro repetições por tratamento, adicionando às seguintes concentrações de Cu (como nitrato de Cu): 0, 75, 150, 300, 600, 800, 1000, 1200 mg kg-¹ de solo seco. Foram realizadas medidas das variáveis biológicas matéria seca da parte aérea (MSPA), altura da planta, diâmetro do caule e número de folhas, além disso foi determinado o teor de Cu na MSPA. No LVAd, a ordem decrescente de tolerância à fitotoxicidade do Cu foi: feijão, milho, soja, trigo, rabanete e arroz. No entanto, no LVdf, a ordem decrescente foi: milho, soja, rabanete, trigo, feijão e arroz. A espécie que revelou maior sensibilidade às altas concentrações de Cu no solo foi o arroz e a que apresentou menor sensibilidade foi o milho.
Assuntos
Cobre/efeitos adversos , Cobre/toxicidade , Grão Comestível , Solo/químicaRESUMO
In previous studies, we have shown that copper (Cu) is significantly accumulated in various tissues of killifish Poecilia vivipara following chronic exposure. Also, we showed that chronic metal exposure disrupted energy production and growth in this species. In the present study, we aimed to evaluate if chronic exposure to this metal could also affect reproductive parameters of P. vivipara males (sperm quality). In order to test that, newborn (<24â¯h-old) fish were exposed to two concentrations of waterborne Cu (5 and 9⯵g/L) for 345 days. After exposure, fish were euthanized and the testes were collected for sperm analysis. We could observe that exposed animals had reduced sperm motility and period of motility. Also, the sperm of exposed fish had reduced plasma membrane integrity, mitochondrial functionality and DNA integrity when compared to sperm of control animals. It is suggested that the well-known association of Cu with elevated oxidative damage, endocrine disruption and energetic disturbance are involved with the observed outcomes. The results obtained in the present study show that chronic exposure to environmentally relevant concentrations of waterborne Cu caused reductions in all parameters used to evaluate sperm quality. Therefore, it is concluded that life-time exposure to this metal may disrupt fish reproduction and negatively affect the maintenance of its populations.
Assuntos
Cobre/efeitos adversos , Cobre/química , Fundulidae/crescimento & desenvolvimento , Metais/efeitos adversos , Motilidade dos Espermatozoides/imunologia , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/química , Animais , Humanos , Masculino , Metais/químicaRESUMO
Copper nanoparticles (NCu) may co-exist with other pollutants in agricultural soils, such as pesticides. However, this has been little evaluated yet. Thus, possible effects of the simultaneous applications of pesticides and NCu on biogeochemical cycles are expected, for example on the nitrogen cycle. Therefore, the aim of this work was to evaluate the effect of simultaneous application of the herbicide atrazine (ATZ) and NCu on the abundance of total bacteria and nitrifying communities: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Moreover, the ATZ dissipation was evaluated. A soil-plant system containing ATZ at field dose (3â¯mg a.i. kg-1) was mixed with two doses of NCu (0.05% or 0.15% w/w). Changes in the abundance of 16S rRNA and ammonia monooxygenase (amoA) genes of AOA and AOB were evaluated by real-time quantitative PCR (qPCR) at three sampling times (1, 15 and 30â¯days). The residual ATZ and nitrate production were also measured. The results showed significant differences in microbial composition and abundance over the 30â¯days of the experiment. Particularly, an initial decrease was observed in total bacterial abundance due to the presence of ATZ and NCu respect to ATZ alone (~60%). The abundance of AOA was also remarkably reduced (~85%), but these communities gradually recovered towards the end of the experiment. Conversely, AOB abundance initially increased (>100%) and remained mainly unaltered in soil exposed to ATZ and NCu 0.15% w/w, where nitrate formation was also constant. Moreover, NCu decreased the ATZ dissipation, which was translated in a 2-fold increase on the ATZ half-life values (T1/2). This study demonstrates that the simultaneous presence of NCu and ATZ may represent a risk for the total bacteria present in soil and sensitive microorganisms such as nitrifying communities, and changes in the dissipation of the pesticide could influence this process.
Assuntos
Archaea/fisiologia , Atrazina/efeitos adversos , Fenômenos Fisiológicos Bacterianos , Cobre/efeitos adversos , Herbicidas/efeitos adversos , Nanopartículas Metálicas/efeitos adversos , Poluentes do Solo/efeitos adversos , Genes Bacterianos , Ciclo do Nitrogênio , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Microbiologia do SoloRESUMO
Neste trabalho foram sintetizados complexos de cobre(II) com derivados imínicos da isatina, incluindo isatinas bromadas semelhantes a compostos encontrados em gastrópodes, a fim de compará-los com o composto já produzido e investigado [Cu(isaepy)], complexo de cobre(II) com base de Schiff feita a partir da isatina e 2-aminoetilpiridina. A isatina é um oxindol produzido em algumas plantas, também encontrado no tecido de mamíferos, com propriedades antitumorais naturais. Isatinas bromadas foram previamente constatadas como mais citotóxicas frente a células tumorais do que a isatina sem substituições. O objetivo principal foi verificar se a presença de bromo nos compostos análogos ao [Cu(isaepy)] levaria a um aumento da atividade antitumoral, assim como maior interação com DNA, alvo usual de metalofármacos. Depois de sintetizados, os compostos foram caracterizados por análise elementar (CHN), espectroscopia no infravermelho, espectroscopia UV/Vis e EPR. Foram feitos testes de citotoxicidade pelo método MTT com células de sarcoma uterino (MES-SA e MES-AS/Dx5, esta última resistente a doxorrubicina), adenocarcinoma cervical (HeLa) e células não cancerosas de fibroblasto humano P4. Adicionalmente, foram feitos testes de interação com DNA por UV/Vis e dicroísmo circular, além de testes de clivagem de DNA plasmidial. De modo geral, foi demonstrado que a simetria tetragonal em torno do cobre, determinada pelo EPR, é importante para a citotoxicidade dos complexos, que dessa forma podem se intercalar ao DNA e impedir sua replicação, por acabar distorcendo a hélice, e pela habilidade de realizarem clivagem oxidativa das fitas. [Cu(isaepy)] e seus análogos bromados demonstraram uma atividade citotóxica muito parecida, assim como grau de interação e clivagem com DNA. Conclui-se que, embora a presença de bromo nos análogos de [Cu(isaepy)] não levem a um aumento de atividade antitumoral, como observado em ligantes correlatos livres, nossos estudos apontam para diferentes fontes naturais (animal ou vegetal) para obtenção de precursores de novos compostos antitumorais
In the present work, copper(II) complexes were synthesized with isatin derived imine ligands, including brominated oxindoles similar to compounds found in gastropods, in order to compare their reactivity with that of [Cu(isaepy)], a Schiff base-copper(II) complex already investigated, obtained with the precursors isatin and 2-aminoethylpyridine. Isatin is a natural oxindole extracted from plants, and also found in mammal tissue, with antitumor properties. Brominated isatins were previously described as much more cytotoxic, towards tumor cells, than unsubstituted isatin. The aim of this work was to verify if the presence of brome in analogue [Cu(isaepy)] compounds would increase their antitumor activity, along with higher DNA interaction, an usual target for metallodrugs. The copper(II) complexes were synthesized and then characterized through elemental analyses (CHN), infrared, UV/Vis and EPR spectroscopies. Cytotoxicity tests were carried out using MTT assay with cells lines MES-SA e MES-SA/Dx5 (uterine sarcome, sensitive and resistent to doxorubicin), HeLa (cervical adenocarcinoma) and non-tumor cells, human fibroblast P4. Additionally, DNA interaction experiments were carried out through UV/Vis spectroscopy and circular dichroism, and at last, DNA cleavage experiments with the studied complexes. In general, it was shown that a tetragonal symmetry around copper, shown by EPR, is very important to the complexes toxicity, since in that way they are able to intercalate DNA, and prevent its replication, as a consequence of double helix distortion, and eventual oxidative cleavage. [Cu(isaepy)] and its brominated analogues demonstrated a very similar cytotoxicity towards cancer cells, as well as quite same level of DNA interaction and cleavage. Although the presence of brome did not increase significantly their antitumor activity, as verified with the free isatin derivatives, our studies pointed to different natural sources to obtain precursors for such new antitumor compounds
Assuntos
DNA , Cobre/efeitos adversos , Isatina/análise , Produtos Biológicos/uso terapêutico , Oxindóis/classificaçãoRESUMO
Ocean warming is increasing and scientific predictions suggest a rise of up to 4°C in sea water temperatures. The combination of a polluted and warmer environment may be detrimental for aquatic species, especially for primary producers such as seaweeds. This study investigated the potential for interactive effects of an increased seawater temperature in a copper-rich environment on the photosynthetic pigments and metabolic compounds of the red seaweed Gelidium floridanum. Seaweed samples were cultivated in a factorial design with temperature (24°C and 30°C), copper (0 and 3 µM), and time (7 and 14 d). The exposure of G. floridanum to copper and 30°C for 7 d resulted in a lower concentration of chlorophyll a, smaller phycobiliprotein rods and lower concentration of soluble sugars. After 14 d of cultivation, a higher concentration of chlorophyll a and soluble sugars could be observed on seaweeds cultivated under 30°C. The accumulation of carotenoids and the release of phenolic compounds indicated specific protective mechanisms against temperature and copper, respectively. Overall, seaweeds grew less when exposed to copper 3 µM at 30°C.
Assuntos
Cobre/efeitos adversos , Aquecimento Global , Pigmentos Biológicos/metabolismo , Rodófitas/metabolismo , Água do Mar/química , Poluentes Químicos da Água/efeitos adversos , Mudança Climática , Temperatura Alta , Oceanos e Mares , Rodófitas/crescimento & desenvolvimentoRESUMO
Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function that was dose- and time-dependent with an IC50 of 1.3 ± 0.2, 5.5 ± 0.5, and 10 ± 0.7 µM, correspondingly. Myocardial oxygen consumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial Ca2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability.
Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Compostos Organometálicos/efeitos adversos , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/química , Cobre/efeitos adversos , Cobre/química , Masculino , Mitocôndrias Cardíacas/metabolismo , Compostos Organometálicos/administração & dosagem , Ratos , Ratos WistarRESUMO
The mechanisms involved in vascular reactivity alterations promoted by copper (Cu) overload were investigated. Thoracic aorta obtained from male Wistar rats were cut into rings and exposed for 1 h to 10 µg/ml Cu. Exposure to Cu decreased the contractile responses of aortic rings to phenylephrine (PHE). Removal of endothelium and subsequent administration of N-nitro-L arginine methyl ester (L-NAME), tetrahydrobiopterin, aminoguanidine, diethyldithiocarbamic acid, catalase, or tetraethylammonium increased contractile responses. Incubation with apocinyn and tiron enhanced the sensitivity to PHE. Data demonstrated that high concentrations of Cu reduced PHE-mediated vascular reactivity which was associated with elevated production of nitric oxide (NO), which was attributed to activation of inducible NO synthase, and elevated levels of hydrogen peroxide probably related to a rise in superoxide dismutase activity and reactive oxygen species generation.
Assuntos
Aorta Torácica/fisiopatologia , Cobre/efeitos adversos , Endotélio Vascular/fisiopatologia , Poluentes Ambientais/efeitos adversos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Oligoelementos/efeitos adversosRESUMO
Mangrove is an important ecosystem in the world. Mangrove ecosystems have a large capacity in retaining heavy metals, and now they are usually considered as sinks for heavy metals. However, the mechanism of why the soil of mangrove ecosystems can retain heavy metal is not certain. In this research, endophytic fungus Purpureocillium sp. A5 was isolated and identified from the roots of Kandelia candel. When this fungus was added, it protected the growth of K. candel under Cu stress. This can be illustrated by analyzing chlorophyll A and B, RWC and WSD to leaves of K. candel. Purpureocillium sp. A5 reduces uptake of Cu in K. candel and changes the pH characterization of soil. Furthermore, A5 increase the concentration of Cu complexes in soil, and it enhanced the concentration of carbonate-bound Cu, Mn-Fe complexes Cu and organic-bound Cu in soil. Nevertheless, a significant reduction of the Cu ion was noted among A5-treated plants. This study is significant and illustrates a promising potential use for environmental remediation of endophytes, and also may partially explain the large capacity of mangrove ecosystems in retaining heavy metals.(AU)
Assuntos
Endófitos , Hypocreales , Rhizophoraceae , Cobre/efeitos adversos , Fungos , Áreas Alagadas , Metais PesadosRESUMO
Copper-based drugs, Casiopeinas (Cas), exhibit antiproliferative and antineoplastic activities in vitro and in vivo, respectively. Unfortunately, the clinical use of these novel chemotherapeutics could be limited by the development of dose-dependent cardiotoxicity. In addition, the molecular mechanisms underlying Cas cardiotoxicity and anticancer activity are not completely understood. Here, we explore the potential impact of Cas on the cardiac mitochondria energetics as the molecular mechanisms underlying Cas-induced cardiotoxicity. To explore the properties on mitochondrial metabolism, we determined Cas effects on respiration, membrane potential, membrane permeability, and redox state in isolated cardiac mitochondria. The effect of Cas on the mitochondrial membrane potential (Δψm) was also evaluated in isolated cardiomyocytes by confocal microscopy and flow cytometry. Cas IIIEa, IIgly, and IIIia predominately inhibited maximal NADH- and succinate-linked mitochondrial respiration, increased the state-4 respiration rate and reduced membrane potential, suggesting that Cas also act as mitochondrial uncouplers. Interestingly, cyclosporine A inhibited Cas-induced mitochondrial depolarization, suggesting the involvement of mitochondrial permeability transition pore (mPTP). Similarly to isolated mitochondria, in isolated cardiomyocytes, Cas treatment decreased the Δψm and cyclosporine A treatment prevented mitochondrial depolarization. The production of H2O2 increased in Cas-treated mitochondria, which might also increase the oxidation of mitochondrial proteins such as adenine nucleotide translocase. In accordance, an antioxidant scavenger (Tiron) significantly diminished Cas IIIia mitochondrial depolarization. Cas induces a prominent loss of membrane potential, associated with alterations in redox state, which increases mPTP opening, potentially due to thiol-dependent modifications of the pore, suggesting that direct or indirect inhibition of mPTP opening might reduce Cas-induced cardiotoxicity.
Assuntos
Antineoplásicos , Cobre , Mitocôndrias Cardíacas/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Cobre/efeitos adversos , Cobre/farmacologia , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/patologia , Permeabilidade/efeitos dos fármacos , RatosRESUMO
In the present study, thirty-five Nellore bulls were used to determine the effects of two levels and two sources (organic and inorganic) of Cu supplementation on the oxidative stability of lipids, measured by the thiobarbituric acid-reactive substance (TBARS) test, meat colour and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities. The following treatments were used: (1) control (C) - basal diet without supplementation of Cu (7 mg Cu/kg DM); (2) I10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper sulphate (inorganic form); (3) I40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper sulphate; (4) O10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper proteinate (organic form); (5) O40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper proteinate. Lipid oxidation was determined in meat samples exposed to display, modified atmosphere (MA) and vacuum packaging (VC) conditions and in liver samples using the TBARS test. These samples were also evaluated for meat discolouration after exposure to air. The activities of SOD and GSH-Px enzymes were determined in liver samples. In display, MA and VC conditions, the TBARS values of samples from animals supplemented with 40 mg Cu/kg DM were lower than those of samples from control animals. There was no effect of treatment on the colour variables (L*, a*, b*). There was also no significant effect of treatment on hepatic TBARS concentrations and GSH-Px activity. Supplementation with Cu at 40 mg/kg, regardless of the source, induced higher hepatic SOD activity compared with the control treatment. In conclusion, Cu supplementation improved the oxidative stability of lipids in samples exposed to display, MA and VC conditions, demonstrating the antioxidant effect of this mineral.
Assuntos
Cobre/uso terapêutico , Deficiências Nutricionais/veterinária , Dieta/veterinária , Peroxidação de Lipídeos , Fígado/enzimologia , Carne/análise , Músculo Esquelético/metabolismo , Animais , Animais Endogâmicos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antioxidantes/uso terapêutico , Brasil , Bovinos , Cobre/administração & dosagem , Cobre/efeitos adversos , Cobre/deficiência , Deficiências Nutricionais/dietoterapia , Dieta/efeitos adversos , Embalagem de Alimentos , Qualidade dos Alimentos , Armazenamento de Alimentos , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Pigmentação , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
OBJECTIVES: Copper (Cu) is widely used in industry for the manufacture of a vast range of goods including Cu-intrauterine devices (IUDs), electronic products, agrochemicals, and many others. It is also one of the trace elements essential to human health in the right measure and is used as a parenteral supplement in patients unable to ingest food. Elevated Cu levels have been found in the plasma of women using Cu-IUDs and in farmers working with Cu-based pesticides. However, possible alterations due to Cu overload in the brain have been poorly studied. Therefore, the aim of this study was to investigate the effects of Cu administration on rat brain in Cu-sufficient and Cu-deficient animals fed on semi-synthetic diets with different doses of Cu (7 or 35 ppm). METHODS: We aimed to investigate the effects of Cu administration using two routes of administration: oral and intraperitoneal (IP). Male Wistar rats were feeding (one month) a complete (7 ppm) or a deficient (traces) Cu diets subdivided into three categories oral-, intraperitoneal- (or both) supplemented with copper carbonate (7 to 35 ppm). Cu content in plasma, brain zones (cortex and hippocampus), antioxidant enzyme activities, and protease systems involved in programmed cell death were determined. RESULTS: The results show that Cu levels and the concentration of Cu in plasma and brain were dose-dependent and administration route-dependent and demonstrated a prooxidative effect in plasma and brain homogenates. Oxidative stress biomarkers and antioxidative enzyme activity both increased under Cu overload, these effects being more noticeable when Cu was administered IP. Concomitantly, brain lipids from cortex and hippocampus were strongly modified, reflecting Cu-induced prooxidative damage. A significant increase in the activities of calpain (milli- and micro-) and caspase-3 activity also was observed as a function of dose and administration route. CONCLUSION: The findings of this study could be important in evaluating the role of Cu in brain metabolism and neuronal survival.
Assuntos
Encéfalo/efeitos dos fármacos , Carbonatos/efeitos adversos , Carbonatos/sangue , Cobre/efeitos adversos , Cobre/sangue , Administração Oral , Animais , Biomarcadores/sangue , Encéfalo/metabolismo , Carbonatos/administração & dosagem , Caspase 3/genética , Caspase 3/metabolismo , Cobre/administração & dosagem , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de OxigênioRESUMO
The estuarine crab Neohelice granulata was exposed (96 h) to a sublethal copper concentration under two different physiological conditions (hyperosmoregulating crabs: 2 ppt salinity, 1 mg Cu/L; isosmotic crabs: 30 ppt salinity, 5 mg Cu/L). After exposure, gills (anterior and posterior) were dissected and activities of enzymes involved in glycolysis (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase), Krebs cycle (citrate synthase), and mitochondrial electron transport chain (cytochrome c oxidase) were analyzed. Membrane potential of mitochondria isolated from anterior and posterior gill cells was also evaluated. In anterior gills of crabs acclimated to 2 ppt salinity, copper exposure inhibited hexokinase, phosphofructokinase, pyruvate kinase, and citrate synthase activity, increased lactate dehydrogenase activity, and reduced the mitochondrial membrane potential. In posterior gills, copper inhibited hexokinase and pyruvate kinase activity, and increased citrate synthase activity. In anterior gills of crabs acclimated to 30 ppt salinity, copper exposure inhibited phosphofructokinase and citrate synthase activity, and increased hexokinase activity. In posterior gills, copper inhibited phosphofructokinase and pyruvate kinase activity, and increased hexokinase and lactate dehydrogenase activity. Copper did not affect cytochrome c oxidase activity in either anterior or posterior gills of crabs acclimated to 2 and 30 ppt salinity. These findings indicate that exposure to a sublethal copper concentration affects the activity of enzymes involved in glycolysis and Krebs cycle, especially in anterior (respiratory) gills of hyperosmoregulating crabs. Changes observed indicate a switch from aerobic to anaerobic metabolism, characterizing a situation of functional hypoxia. In this case, reduced mitochondrial membrane potential would suggest a decrease in ATP production. Although gills of isosmotic crabs were also affected by copper exposure, changes observed suggest no impact in the overall tissue ATP production. Also, findings suggest that copper exposure would stimulate the pentose phosphate pathway to support the antioxidant system requirements. Although N. granulata is very tolerant to copper, acute exposure to this metal can disrupt the energy balance by affecting biochemical systems involved in carbohydrate metabolism.
Assuntos
Braquiúros/efeitos dos fármacos , Cobre/efeitos adversos , Brânquias/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Salinidade , Aclimatação , Animais , Braquiúros/enzimologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Citrato (si)-Sintase/antagonistas & inibidores , Citrato (si)-Sintase/metabolismo , Ciclo do Ácido Cítrico , Exposição Ambiental/efeitos adversos , Ativação Enzimática , Inibidores Enzimáticos/efeitos adversos , Brânquias/enzimologia , Glicólise , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/metabolismo , Fosfofrutoquinases/antagonistas & inibidores , Fosfofrutoquinases/metabolismo , Piruvato Quinase/antagonistas & inibidores , Piruvato Quinase/metabolismo , Poluentes Químicos da Água/efeitos adversos , Equilíbrio HidroeletrolíticoRESUMO
En el presente estudio se determinaron las concentraciones séricas de cobre (CuS) y de cinc (ZnS) en escolares de am - bos sexos, con edades entre 7-14 años, que viven en la ciudad de Barquisimeto, estado Lara, Venezuela. La muestra consistió de 195 estudiantes (112 niñas y niños 83) clínicamente sanos, que no mostraron evidencias de enfermedades crónicas o infecciones agudas o procesos inflamatorios al momento de la evaluación clínica. Las concentraciones séricas de los metales se determinaron por espectrofotometría de absorción atómica. La influencia entre los valores séricos de los elementos traza, la edad y el género también se investigó. Las concentraciones séricas promedio de Zn y Cu fueron de 0,97±0,17 y 0,90±0,18µg/mL, respectivamente. No hubo diferencias significativas en los niveles séricos de cinc entre niños y niñas en los diferentes grupos de edad. Los valores séricos de cobre son mayores en las niñas (p <0,05) que en los niños. Los intervalos de referencia para estos elementos traza en suero se calcularon siguiendo los criterios del CLSI y fueron de 0,70 a 1,30 y 0,70 a 1,20 µg/mL para cinc y cobre, respectivamente. La mayoría de los síntomas clínicos de la deficiencia marginal de estos elementos traza no son muy específicos, y su diagnóstico no es fácil. En conclusión, los valores de Cu y Zn, y los intervalos de referencia, de este estudio pueden ser útiles en el diagnóstico de estas deficiencias marginales. Las carencias marginales o graves de estos elementos pueden considerarse factores de riesgo para diversas enfermedades de importancia en salud pública.
In the present study the serum concentrations of copper (CuS) and zinc (ZnS) in schoolchildren of both genders, aged between 7-14 yr. living in the city of Barquisimeto, Lara State, Venezuela. The sample consisted of 195 students (112 girls and 83 boys) clinically healthy at the time of evaluation, which showed no evidence of any chronic disease or acute infections or inflammatory processes. Serum concentrations of me tals were determined by flame atomic absorption spectrophotometry. The relation between serum values of trace elements, age and gender was also investigated. Mean serum concentrations of Zn and Cu were 0,97 ±0,17 and 0,90±0,18 µg/mL, respectively. There were not significant differences in serum zinc between boys and girls in the different age groups. Serum copper values are higher in girls (p<0.05) than in boys. Reference intervals for these serum trace elements were calculated following the criteria of CLSI and were 0,70 to 1,30 and 0,70 to 1,20 µg/mL for zinc and copper, respectively. Most of the clinical symptoms of trace element deficiency are not very specific, and the diagnosis of this deficiency is not easy. In conclusion, the values of Zn and Cu, and the reference intervals, of the present study can be useful in the diagnosis of these marginal trace elements deficiency. Marginal or severe trace element imbalances can be considered risk factors for several diseases of public health importance.
Assuntos
Humanos , Masculino , Feminino , Criança , Análise Espectral , Zinco/metabolismo , Espectrofotometria Atômica , Cobre/efeitos adversos , Valores de Referência , Saúde Pública , Substâncias TóxicasRESUMO
The proposed curative properties of copper(II)-non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous copper(II)-NSAID complexes with enhanced anti-inflammatory activity. In this work, the antinociceptive and toxic effects of two new coordination complexes: Cu2(fen)4(caf)2 [fen: fenoprofenate anion; caf: caffeine] and Cu2(fen)4(dmf)2 [dmf: N-N'-dimethylformamide] were evaluated in mice. The antinociceptive effect was evaluated with two models: acetic acid-induced writhing response and formalin test. For the sub-acute exposure, the complexes were added to the diet at different doses for 28days. Behavioral and functional nervous system parameters in a functional observational battery were assessed. Also, hematological, biochemical and histopathological studies were performed. Cu2(fen)4(caf)2 and Cu2(fen)4(dmf)2 significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test with respect to the control and fenoprofen salt groups. The sub-acute exposure to Cu2(fen)4(caf)2 complex increased the motor activity, the number of rearings and the arousal with respect to the control and fenoprofen salt groups. These impaired parameters in mice exposed to Cu2(fen)4(caf)2 can be attributable to the presence of caffeine as stimulating agent. On the other hand, all exposed groups decreased the urine pools in the functional observational battery and increased the plasmatic urea. These effects could be due to the decrease in the glomerular filtration caused by NSAIDs. In conclusion, both complexes Cu2(fen)4(dmf)2 and Cu2(fen)4(caf)2 were more potent antinociceptive agents than fenoprofen salt. Sub-acute exposure to different doses of these complexes did not produce significant changes in the parameters that evaluate toxicity.
Assuntos
Dor Abdominal/tratamento farmacológico , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Complexos de Coordenação/uso terapêutico , Fenoprofeno/uso terapêutico , Inflamação/tratamento farmacológico , Dor Abdominal/sangue , Dor Abdominal/prevenção & controle , Dor Abdominal/urina , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Nível de Alerta/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/efeitos adversos , Cafeína/química , Cafeína/uso terapêutico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/uso terapêutico , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/química , Cobre/administração & dosagem , Cobre/efeitos adversos , Cobre/química , Dimetilformamida/administração & dosagem , Dimetilformamida/química , Relação Dose-Resposta a Droga , Feminino , Fenoprofeno/administração & dosagem , Fenoprofeno/efeitos adversos , Fenoprofeno/química , Insuficiência Hepática/induzido quimicamente , Inflamação/sangue , Inflamação/prevenção & controle , Inflamação/urina , Camundongos , Medição da Dor , Distribuição Aleatória , Insuficiência Renal/induzido quimicamenteRESUMO
A study was conducted to evaluate the predictive diagnostic value of different copper (Cu) parameters as indicators of average daily gain (ADG) in growing calves. The effects in calves of cow Cu supplementation in the last one-third gestation period were also evaluated. Five supplementation trials, with a total of 300 calves, were carried out. Two groups of 30 calves were randomly assigned to each trial, one group was parenterally supplemented (SG) and the other was not supplemented (NSG). Trials began when calves were three-month-old and ended at weaning time. At each sampling calves were weighed and blood was taken to determine Cu concentrations in plasma, Whole Blood (WB), Red Cells (RC) and Packed Cell Volume (PCV). Liver samples from six animals of each group were taken both at the beginning and at the end of the trial. In two trials the mothers of the SG received Cu supplementation at the last one- third gestation period. Four of the five trials exhibited low ADG in the NSGs. In these groups, plasma Cu concentration decreased rapidly before low ADG was detected, which occurred with values remaining below 25µg/dl. The decrease of RC Cu concentration was considerably slow. WB showed an intermediate position. PCV in the SGs was higher than in the NSGs in all trials. Cow supplementation was insufficient to generate a liver storage able to last after calves reached the 3 months of age. These data could be useful to predict the risk of low ADG in grazing calves.
Foi realizado um estudo para predisser o valor diagnóstico de diferentes parâmetros de cobre (Cu) como indicadores de ganho médio diário (ADG) na criação de bezerros. Também foram avaliados os efeitos da suplementação com Cu nas vacas no último terço da gestação. Cinco ensaios de suplementação, com um total de 300 bezerros, foram realizados. Dois grupos de 30 bezerros foram atribuídos aleatoriamente em cada proba, um grupo foi parenteralmente suple mentado (SG) e o outro não foi suplementado (NSG). Os ensaios começaram quando os bezerros tinham três meses de idade e terminou ao tempo do destete. Em cada ensaio os bezerros foram pesados e mostras do sangue foi tomada para determinar as concentrações Cu no plasma, sangue total (WB), eritrócitos (RC) e hematócrito (PCV). Amostras de fígado foram colhidas em seis animais de cada grupo tanto no início quanto no final do ensaio As mães do SG receberam suplementação de Cu no último terço da gestação em dois ensaios. Quatro dos cinco ensaios apresentavam baixa ADG nos NSGs. Nesses grupos, a concentração plasmática de Cu diminuiu rapidamente antes que a baixa do ADG fossei detectada, o que ocorreu com os valores abaixo 25 µg/d. A diminuição da concentração de RC Cu foi bastante lenta. WB mostrou uma posição intermédia. PCV nos SGs foi mais elevado do que nos NSGs em todos os ensaios. A suplementação das vacas foi insuficiente para gerar um armazenamento hepático capaz de durar até os 3 meses de idade dos bezerros. Estes dados poderiam ser úteis para prever o risco de baixa ADG em bezerros em pastagem.