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1.
Vet Clin North Am Food Anim Pract ; 36(1): 89-107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32029191

RESUMO

It is increasingly difficult to manage and control gastrointestinal nematode parasites in pasture-based ruminant livestock operations because of the high prevalence of anthelmintic resistance. Anthelmintics should be combined with alternative forms of control. Sustainable tools include copper oxide wire particles and condensed tannin-rich plants, which target primarily Haemonchus contortus in small ruminants. Nematophagous fungi reduce larvae on pasture and target nematode larvae in feces of most livestock species. In addition, and perhaps most importantly, genetic selection focuses on parasite resistance. Producers should use as many tools as possible to minimize the need for pharmaceutical interventions and optimize animal production.


Assuntos
Hemoncose/veterinária , Animais , Anti-Helmínticos/administração & dosagem , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/parasitologia , Cobre/administração & dosagem , Doenças das Cabras/tratamento farmacológico , Doenças das Cabras/parasitologia , Cabras , Hemoncose/tratamento farmacológico , Haemonchus/isolamento & purificação , Gado/parasitologia , Proantocianidinas/administração & dosagem , Ruminantes/parasitologia , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia
2.
PLoS One ; 15(2): e0228864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092072

RESUMO

The integration of metallic or ceramic nanoparticles in polymer matrices has improved the antimicrobial and antifungal behavior, resulting in the search for composites with increased bactericidal and antimycotic properties. A polycaprolactone fibers with copper oxide nanoparticles was prepared. Polycaprolactone-copper fibers (PCL- CuONPs) were prepared into two major steps in situ method: (a) Synthesis of CuO particles, then (b) incorporation of polycaprolactone to electrospun process. The first step is the reduction of Cu+2 ions by gallic acid in N,N-dimethylformamide and tetrahydrofuran solution with the simple addition of polycaprolactone in the solution for the second electrospun step. Raman spectra provide information about the nature of the copper oxide synthesized. There are three Raman peaks in the sample, at 294 and 581 cm-1 and a very broad band from 400 to 600 cm-1 which are characteristics bands for CuO. Scanning electron microscopy (TEM) revealed copper oxide nanoparticles with semispherical shapes with diameter 35 ±11 nm. Dynamic light scattering (DLS) analysis showed uniform CuONPs in a range of 88±11 nm. Scanning electron microscopy (SEM) of PCL-CuONps reveled fibers with diameters ranging from 925 to 1080 nm were successfully obtained by electrospinning technique. Orientation, morphology and diameter were influenced by the increment on CuONPs concentration, with the smaller diameter present in samples prepared from low concentrated solutions. The antimycotic applicability of the composite was evaluated to determine the antifungal activity in three species of the genus Candida (Candida albicans, Candida glabrata and Candida tropicalis). PCL-CuONPs exhibit a considerable antifungal effect on all species tested. The preparation of PCL-CuONPs was simple, fast and low-cost for practical application as an antifungal dressing.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cobre/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/química , Candida/ultraestrutura , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanotecnologia , Poliésteres/química , Análise Espectral Raman
3.
Life Sci ; 241: 117139, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31809714

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious lung problem with advancing and diffusive pulmonary fibrosis as the pathologic basis, and with oxidative stress and inflammation as the key pathogenesis. Glycyl-L-histidyl-l-lysine (GHK) is a tripeptide participating into wound healing and regeneration. GHK-Cu complexes improve GHK bioavailability. Thus, the current study aimed to explore the therapeutic role of GHK-Cu on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. METHODS: BLM (3 mg/kg) was administered via tracheal instillation (TI) to induce a pulmonary fibrosis model in C57BL/6j mice 21 days after the challenge of BLM. GHK-Cu was injected intraperitoneally (i.p.) at different dosage of 0.2, 2 and 20 µg/g/day in 0.5 ml PBS on alternate day. The histological changes, inflammation response, the collagen deposition and epithelial-mesenchymal transition (EMT) was evaluated in the lung tissue. EMT was evaluated by ɑ-SMA and fibronectin expression in the lung tissue. NF-κB p65, Nrf2 and TGFß1/Smad2/3 signalling pathways were detected by immunoblotting analysis. RESULTS: GHK-Cu complex inhibited BLM-induced inflammatory and fibrotic pathological changes, alleviated the inflammatory response in the BALF by reducing the levels of the inflammatory cytokines, TNF-ɑ and IL-6 and the activity of MPO as well as reduced collagen deposition. In addition, the GHK-Cu treatment significantly reversed the MMP-9/TIMP-1 imbalance and partially prevented EMT via Nrf2, NF-κB and TGFß1 pathways, as well as Smad2/3 phosphorylation. CONCLUSIONS: GHK-Cu presented a protective effect in BLM-induced inflammation and oxidative stress by inhibiting EMT progression and suppressing TGFß1/Smad2/3 signalling in pulmonary fibrosis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bleomicina/toxicidade , Cobre/administração & dosagem , Oligopeptídeos/administração & dosagem , Fibrose Pulmonar/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/toxicidade , Colágeno/metabolismo , Cobre/química , Citocinas/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligopeptídeos/química , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-31877432

RESUMO

Gandou Decoction (GDD), a well-known traditional Chinese medicine prescription, has been widely used for decades in clinical practice to treat Wilson's disease (WD) in China. However, due to lack of in vivo metabolism research, the absorbed components and metabolites of GDD have not been fully elucidated. In this study, a rapid and high-throughput ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) was applied to rapidly identify prototypes and metabolites after oral administration of GDD. On this basis, the possible metabolic pathways of the main prototypes were proposed between normal and copper-laden rats. As a result, a total of 89 GDD-related xenobiotics were detected in normal dosed rats, including 83 (36 prototypes and 47 metabolites) in plasma and 52 (21 prototypes and 31 metabolites) in liver; a total of 77 GDD-related xenobiotics were detected in copper-laden dosed rats, including 68 (31 prototypes and 37 metabolites) in plasma and 42 (19 prototypes and 23 metabolites) in liver. Our findings showed that anthraquinones, alkaloids and protostane triterpenoids as well as a few saponins, flavonoids, tannins and curcuminoids were the main absorbed chemical components of GDD in rat plasma; anthraquinones, protostane triterpenoids and curcuminoids were the major components in rat liver. Glucuronidation and sulfation were deduced to be the predominant metabolic pathways of GDD. Methylation, acetylation, reduction, hydroxylation, demethylation and deglycosylation were often occurred in the metabolic process. Furthermore, the holistic metabolic profile of GDD revealed that copper-laden rats and normal rats had certain differences in drug absorption and metabolism. This study offered a solid basis for ascertaining bioactive components and action mechanism of GDD.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas , Fígado , Espectrometria de Massas em Tandem/métodos , Alcaloides/análise , Alcaloides/farmacocinética , Animais , Antraquinonas/análise , Antraquinonas/farmacocinética , Cobre/administração & dosagem , Cobre/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica , Ratos , Triterpenos/análise , Triterpenos/farmacocinética
5.
J Anim Sci ; 97(10): 4242-4247, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581297

RESUMO

Two performance studies were conducted to investigate the effects of 3 different sources of Cu on production parameters of piglets. A total of 256 piglets weaned at 24 ± 2 d were randomly allocated into 4 treatments with 10 or 8 replicates per treatment of 4 or 3 piglets per pen in Exp. 1 and 2, respectively. The experimental period was divided into 3 feeding phases: Phase 1 (24 to 35 d), Phase 2 (36 to 49 d), and Phase 3 (50 to 70 d). Treatments included a Control group (fed 10 mg/kg of Cu from CuSO4), a group fed 160 mg/kg of either CuSO4 (CuSO4-160) or tri-basic copper chloride (TBCC), and a group fed Cu methionine hydroxy analogue chelated (Cu-MHAC) at 150, 80, and 50 mg/kg in Phases 1, 2, and 3, respectively. The methionine value of Cu-MHAC was accounted during diet formulation to achieve the same levels of methionine across treatments. Phases 1 and 2 diets contained 2,200 and 1,500 ppm of ZnO, respectively; and antibiotics were used as growth promoters. Performance parameters were analyzed as completely randomized block design, in which each experiment was considered as a block. In trial 2, blood serum and mucosal samples, from the fundic region of the stomach, were collected from 1 piglet per replicate at day 70 and tested for serum growth hormone levels (GH) and ghrelin mRNA expression, respectively. The contrast between Cu-MHAC vs. CuSO4-160 + TBCC showed that piglets fed Cu-MHAC exhibited better feed conversion ratio (FCR) in all feeding phases compared with feeding inorganic Cu (P < 0.05). Overall, feeding Cu-MHAC improved body weight (BW), BW gain, feed intake (FI), and FCR vs. Control diet fed piglets; yet, it improved BW and FCR vs. TBCC fed piglets, and improved BW, BW gain, and FI vs. CuSO4-160 fed piglets (P < 0.05). Feeding TBCC promoted similar performance than feeding CuSO4-160, regardless of age (P > 0.05). Both ghrelin expression and growth hormone serum levels were significantly increased by feeding Cu-MHAC vs. Control diet fed animals (P < 0.01). Feeding CuSO4-160 upregulated ghrelin expression vs. Control (P < 0.01) while GH serum levels and ghrelin expression did no change by feeding TBCC compared with Control diet fed animals (P > 0.05). It was concluded that feeding Cu-MHAC at the levels tested herein can improve growth performance of piglets beyond feeding 160 ppm of either CuSO4 or TBCC, which may be partially explained by the increased expression of ghrelin and GH serum levels.


Assuntos
Ração Animal/análise , Cobre/administração & dosagem , Suplementos Nutricionais/análise , Grelina/genética , Hormônio do Crescimento/sangue , Suínos/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Feminino , Masculino , Metionina/análogos & derivados , Metionina/química , RNA Mensageiro/genética , Distribuição Aleatória , Estômago/fisiologia , Suínos/genética , Suínos/crescimento & desenvolvimento , Desmame , Ganho de Peso/efeitos dos fármacos
7.
J Anim Sci ; 97(11): 4619-4624, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31563941

RESUMO

The current study compared the effect of hydroxychloride trace minerals (HTM) with the effect of inorganic trace minerals (ITM) on growth performance and carcass quality in grower-finisher pigs. The results of 6 studies conducted throughout Europe were combined into one meta-analysis. All included studies were performed using pigs from about 19 kg of body weight until slaughter. In all studies, 2 different mineral sources were compared, HTM and sulfates as ITM. Zn from either HTM or ITM was added at a level of 80 ppm to the diet, and Cu was added at a level of 15 ppm from the same source as Zn. In most studies, an additional treatment was included in which 20 ppm Zn was used from either source in combination with 15 ppm Cu from the same source. Diets were fed in 3 phases according to local commercial standards. The body weight, average daily gain, average daily feed intake, and gain:feed ratio were measured at the end of each phase. At the end of each study, the carcass yield, back fat thickness, and lean meat percentage were measured at commercial slaughterhouses. The meta-analysis was conducted using a MIXED model in SAS taking into account the within-study and between-study variation. The comparison was done only between HTM and ITM added at the same Zn level. No statistical differences were observed for growth performance or carcass characteristics between the mineral sources in pigs fed 20 ppm Zn. When 80 ppm Zn was used, a significant improvement in lean meat percentage was observed in pigs fed HTM compared with pigs fed ITM. In the overall study period, there was a tendency towards an increased gain:feed ratio in pigs fed 80 ppm Zn from HTM. In the last feeding phase, before slaughter gain:feed ratio and average daily gain were both significantly improved by 3.9%. In conclusion, HTM addition improved growth performance and lean meat percentage in grower-finisher pigs.


Assuntos
Ração Animal/análise , Carne Vermelha/normas , Suínos/fisiologia , Oligoelementos/administração & dosagem , Animais , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cobre/administração & dosagem , Dieta/veterinária , Europa (Continente) , Feminino , Masculino , Suínos/crescimento & desenvolvimento , Zinco/administração & dosagem
8.
Mar Pollut Bull ; 149: 110556, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546108

RESUMO

Copper (Cu) in an essential trace metal but it can also contaminate coastal waters at high concentrations mainly from agricultural run-off and mining activities which are detrimental to marine organisms including seagrasses. The molecular mechanisms driving Cu toxicity in seagrasses are not clearly understood yet. Here, we investigated the molecular responses of the Australian seagrass, Z. muelleri at the whole transcriptomic level after 7 days of exposure to 250 µg Cu L-1 and 500 µg Cu L-1. The leaf-specific whole transcriptome results showed a concentration-dependent disturbance in chloroplast function, regulatory stress responses and defense mechanisms. This study provided new insights into the responses of seagrasses to trace metal stress and reports possible candidate genes which can be considered as biomarkers to improve conservation and management of seagrass meadows.


Assuntos
Cobre/toxicidade , Poluentes Químicos da Água/toxicidade , Zosteraceae/efeitos dos fármacos , Zosteraceae/genética , Organismos Aquáticos , Cobre/administração & dosagem , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Poluentes Químicos da Água/administração & dosagem
9.
Exp Parasitol ; 205: 107735, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381870

RESUMO

Two experiments were performed to determine whether oral administration of copper oxide capsules controlled helminthic infections in Lacaune sheep without acute collateral effects on animal health. In experiment 1, 48 multiparous lactating sheep (60.1 ±â€¯8.5 kg) were stratified according to initial number of eggs (Haemonchus contortus) per gram of feces (EPG) and were assigned randomly to 1 of two treatments (24 sheep/treatment): no oral administration (control) or oral administration of two copper capsules (treated; approximately 58 mg copper/kg body weight). Blood and fecal samples were collected on days 0, 15 and 45. Animals treated with copper capsules showed lower of EPG, eosinophils, acetylcholinesterase (AChE) in whole blood, and lower butyrylcholinesterase (BChE) activity in serum. Treated sheep had higher erythrocyte numbers, hemoglobin concentrations, hematocrit, and lymphocyte numbers. In experiment 2, 12 male lambs negative for helminths and coccidia were assigned randomly to one of two treatments (six lambs/treatment): control or treated (one copper capsule; approximately 58 mg copper/kg body weight); the experiment was designed to determine whether the results of experiment 1 were due to treatment or parasitism. Blood samples were collected on days 0, 5, 10 and 15 and fecal samples were collected on days 0, 7 and 15. Treated animals showed greater concentrations of lymphocytes; however, treatment had no effect on other hemogram variables, AChE and BChE activities, or levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, urea, albumin, total protein, and reactive oxygen species. These data suggest that copper capsules in dairy sheep efficiently controlled H. contortus infections. Treatment was not harmful to lambs during the first 15 days, i.e. there were no signs of acute toxicity.


Assuntos
Cobre/administração & dosagem , Hemoncose/veterinária , Helmintíase Animal/tratamento farmacológico , Lactação , Doenças dos Ovinos/tratamento farmacológico , Acetilcolinesterase/sangue , Administração Oral , Animais , Butirilcolinesterase/sangue , Cápsulas , Cobre/uso terapêutico , Indústria de Laticínios , Resíduos de Drogas , Eosinófilos/efeitos dos fármacos , Contagem de Eritrócitos/veterinária , Fezes/parasitologia , Feminino , Hemoncose/tratamento farmacológico , Hemoncose/prevenção & controle , Helmintíase Animal/sangue , Helmintíase Animal/prevenção & controle , Hematócrito/veterinária , Hemoglobinas/análise , Contagem de Linfócitos/veterinária , Masculino , Leite/química , Contagem de Ovos de Parasitas/veterinária , Paridade , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/prevenção & controle
10.
Molecules ; 24(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443467

RESUMO

Biofilm-associated tissue and device infection is a major threat to therapy. The present work aims to potentiate ß-lactam antibiotics with biologically synthesized copper oxide nanoparticles. The synergistic combination of amoxyclav with copper oxide nanoparticles was investigated by checkerboard assay and time-kill assay against bacteria isolated from a burn wound and a urinary catheter. The control of biofilm formation and extracellular polymeric substance production by the synergistic combination was quantified in well plate assay. The effect of copper oxide nanoparticles on the viability of human dermal fibroblasts was evaluated. The minimum inhibitory concentration and minimum bactericidal concentration of amoxyclav were 70 µg/mL and 140 µg/mL, respectively, against Proteus mirabilis and 50 µg/mL and 100 µg/mL, respectively, against Staphylococcus aureus. The synergistic combination of amoxyclav with copper oxide nanoparticles reduced the minimum inhibitory concentration of amoxyclav by 16-fold against P. mirabilis and 32-fold against S. aureus. Above 17.5 µg/mL, amoxyclav exhibited additive activity with copper oxide nanoparticles against P. mirabilis. The time-kill assay showed the efficacy of the synergistic combination on the complete inhibition of P. mirabilis and S. aureus within 20 h and 24 h, respectively, whereas amoxyclav and copper oxide nanoparticles did not inhibit P. mirabilis and S. aureus until 48 h. The synergistic combination of amoxyclav with copper oxide nanoparticles significantly reduced the biofilm formed by P. mirabilis and S. aureus by 85% and 93%, respectively. The concentration of proteins, carbohydrates, and DNA in extracellular polymeric substances of the biofilm was significantly reduced by the synergistic combination of amoxyclav and copper oxide nanoparticles. The fibroblast cells cultured in the presence of copper oxide nanoparticles showed normal morphology with 99.47% viability. No cytopathic effect was observed. Thus, the study demonstrated the re-potentiation of amoxyclav by copper oxide nanoparticles.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cobre/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas , beta-Lactamas/farmacologia , Antibacterianos/isolamento & purificação , Infecções Bacterianas/microbiologia , Queimaduras/complicações , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Fibroblastos/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Cateteres Urinários/microbiologia , beta-Lactamas/isolamento & purificação
11.
Exp Parasitol ; 204: 107726, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299264

RESUMO

The aims of this study were to evaluate if the use of copper oxide wire particles, isolated or in association with closantel, in lambs infected with Haemonchus contortus enhances the anthelmintic efficacy of closantel, as well as to evaluate the effects of treatment in hepatic energy metabolism, inflammatory markers and hematological and biochemical tests. The lambs were randomly divided into five groups (6 animals each), as follows: uninfected animals (Control); animals infected with H. contortus (HC); infected and treated with closantel (HC + CL); infected and treated with copper oxide wire particles (HC + Cu); and infected and treated with closantel plus copper oxide wire particles (HC + CL + Cu). The animals of infected groups were infected orally with H. contortus (5,000 L3 -larvae) and on day 14 post infection (p.i) the treatments were initiated. The egg per gram of feces (EPG), butyrylcholinesterase (BuChE), myeloperoxidase (MPO), adenylate kinase (AK) and pyruvate kinase (PK) activities and hematological and biochemical tests were evaluated. Treatments with copper oxide (isolated and associated) were able to reduce the EPG count on days 28, 35, 42 and 49 p.i when compared to HC group, while closantel was able to reduce EPG only from day 35 p.i. Moreover, treatment with closantel (isolated or associated) was able to prevent the inhibition of hepatic AK and PK activities caused by H. contortus infection, which may contribute to efficient intracellular energetic communication in order to maintain the balance between cellular ATP consumption and production. Butyrylcholinesterase and MPO activities were higher in infected lambs compared to uninfected, while treated groups showed lower enzymatic activity compared to the group HC. The use of all therapeutic protocols was able to reduce the EPG count. Based on these evidences, the use of copper oxide plus closantel may be considered an alternative to treat lambs infected by H. contortus.


Assuntos
Anti-Helmínticos/administração & dosagem , Cobre/administração & dosagem , Hemoncose/veterinária , Inflamação/veterinária , Salicilanilidas/administração & dosagem , Doenças dos Ovinos/tratamento farmacológico , Abomaso/metabolismo , Adenilato Quinase/metabolismo , Administração Oral , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Análise Química do Sangue/veterinária , Butirilcolinesterase/sangue , Cápsulas , Metabolismo Energético/efeitos dos fármacos , Contagem de Eritrócitos/veterinária , Fezes/parasitologia , Hemoncose/complicações , Hemoncose/tratamento farmacológico , Hemoncose/metabolismo , Hematócrito/veterinária , Hemoglobinas/análise , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Contagem de Ovos de Parasitas/veterinária , Peroxidase/sangue , Piruvato Quinase/metabolismo , Distribuição Aleatória , Salicilanilidas/farmacologia , Salicilanilidas/uso terapêutico , Ovinos , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/prevenção & controle
12.
J Trace Elem Med Biol ; 55: 170-179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345355

RESUMO

BACKGROUND: Trace elements of copper (Cu) are one of the main forms of ecological noxious waste in freshwater systems that affect the survival and development of organisms. The objective of the current study was to investigate the effects of chronic exposure to Cu on the growth, oxidative stress, immune and biochemical response in the Nile tilapia, Oreochromis niloticus. METHODS: Three groups of O. niloticus were tested as follows; the first group was used as the control (not treated with Cu in water), while the 2nd and 3rd groups were exposed to (low) 40 µg L-1 and (high) 400 µg L-1 concentrations of Cu added to water, respectively. The duration of the experiment, which was conducted in triplicate, was 60 d. End points were evaluated on days 30 and 60. Following 30 d and 60 d of exposure to Cu, the fish were removed from experimental tanks to determine growth. Consequently, blood samples were collected from caudal veins at the end of the trial period (30 d and 60 d) and serum was separated to evaluate different immunological parameters, such as lysozymes (LYZ), respiratory burst activity (RBA) and myeloperoxidase (MPO). Gill and liver tissues were collected for evaluation of Cu and certain biochemical parameters as follows: antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST); non-enzymatic antioxidants such as glutathione (GSH) and metallothionein (MT), and oxidative stress indicators such as malondialdehyde (MDA) and protein carbonyl (PCO). The results pertaining to treatments and the control were compared using two-way ANOVA and Tukey's HSD test. The level of significance was set at P ≤ 0.05. Data were expressed as mean ±â€¯SD. RESULTS: Chronic exposure to Cu did not induce any mortality in fish during the test period. However, following exposure to Cu, growth of fish in the exposed groups was affected more than that in the control group (unexposed to Cu). In addition, accumulation of Cu in the liver tissue was higher than that in the gill tissues of fish exposed to Cu, compared to that in the control. Gill and liver tissues of Cu-exposed fish showed a significant (P ≤ 0.05) reduction in the activities of the antioxidant enzymes, SOD, CAT, GPx, and GST, compared to those of unexposed fish. Non-enzymatic antioxidants, GSH and MT, in gill and liver tissues were significantly increased (P ≤ 0.05) in fish exposed to both concentrations of Cu, compared to those in unexposed fish. Oxidative stress indicators, MDA and PCO in gills and liver of Cu-exposed fish was significantly (P ≤ 0.05) at both tested concentrations, when compared to control group. Non-specific immune response of LYZ, RBA, and MPO activity in serum decreased significantly (P ≤ 0.05) in Cu-exposed fish, compared with that of unexposed fish. CONCLUSION: Overall, the present results highlighted that chronic exposure to Cu ions may exert a strong effect on the antioxidant and immune responses of O. niloticus. Changes in antioxidant enzymes, oxidative stress effects and immune parameters during post-chronic metal exposure may indicate the potential of these parameters as biomarkers of metal toxicity in aquatic ecosystems.


Assuntos
Antioxidantes/toxicidade , Ciclídeos/crescimento & desenvolvimento , Ciclídeos/imunologia , Cobre/administração & dosagem , Cobre/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/administração & dosagem , Ciclídeos/metabolismo , Cobre/imunologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Estresse Oxidativo/imunologia
13.
Arch Anim Nutr ; 73(4): 324-337, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31192701

RESUMO

This experiment was conducted to evaluate the effects of different sources and levels of trace elements on growth performance, carcass composition and mineral excretion levels of broilers. In a completely randomised experimental design, 900 one-day-old male Ross-308 broilers were assigned to 5 treatments, with 6 replicates of 30 birds each. The control group (CITE) was fed with a basal diet containing regular inclusion levels of inorganic trace elements. Treatment groups were supplied with reduced levels (30% and 50% of the regular level) of inorganic (ITE) or organic trace elements (OTE), respectively. Groups 50% ITE, 30% OTE and 50% OTE diets had equivalent average daily gain (ADG), average daily feed intake (ADFI), feed to gain ratio (F/G ratio) and mortality rate compared with group CITE in any phase. However, compared with group CITE chicks in group 30% ITE have lower ADG and ADFI and higher F/G ratio. The carcass yields were not affected by dietary treatments. Compared with group CITE, in groups 30% ITE, 50% ITE, 30% OTE and 50% OTE the shear force values of the breast muscle were only 71.8%, 83.4%, 63.5% and 59.4% (p < 0.05), respectively. Birds received diets containing reduced levels of trace elements had diminished excretions of Mn and Zn throughout the entire period (p < 0.01). In conclusion, the reduced supplementation of trace elements had no or slightly negative impact on growth performance, carcass yield and meat quality, but decreased faecal mineral excretion. Moreover, the trace element supply as OTE played a limited role on performance and excretion and was only partly beneficial for animal performance in case the trace element supply was reduced to 30%.


Assuntos
Galinhas/fisiologia , Dieta/veterinária , Eliminação Intestinal , Minerais/metabolismo , Oligoelementos/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/crescimento & desenvolvimento , Cobre/administração & dosagem , Cobre/química , Cobre/metabolismo , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Fezes/química , Ferro/administração & dosagem , Ferro/química , Ferro/metabolismo , Masculino , Manganês/administração & dosagem , Manganês/química , Manganês/metabolismo , Carne/análise , Distribuição Aleatória , Oligoelementos/administração & dosagem , Zinco/administração & dosagem , Zinco/química , Zinco/metabolismo
14.
Mol Med Rep ; 20(1): 771-778, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180561

RESUMO

The aim of the present study was to evaluate the long­term effect of copper nanoparticles (CuNPs) on cytochrome P450 (CYP450) enzymes in the rat brain. Rats were repeatedly gavaged with different forms of copper sources for 28 days, and the levels of oxidative stress and CYP450 mRNA and protein expression in the rat brain were subsequently analyzed. The results demonstrated that a high dose of CuNPs (200 mg/kg) induced severe oxidative stress in the rat brain along with a decrease in the levels of total superoxide dismutase and glutathione, and an increase in hydroxyl radicals and malondialdehyde. A medium dose of CuNPs reduced CYP450 2C11 and CYP450 3A1 protein expression in the rat brain, whereas high doses of CuNPs resulted in decreased expression of most CYP450 enzyme proteins, and inhibition of pregnane X receptor and constitutive androstane receptor expression. The results suggested that CuNPs may inhibit CYP450 enzyme expression by increasing the levels of oxidative stress and decreasing the expression of nuclear receptors in the rat brain, which affects the metabolism of drugs and endogenous hormones in the brain.


Assuntos
Encéfalo/efeitos dos fármacos , Cobre/efeitos adversos , Sistema Enzimático do Citocromo P-450/genética , Nanopartículas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Cobre/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Feminino , Masculino , Nanopartículas/administração & dosagem , RNA Mensageiro/genética , Ratos
15.
Poult Sci ; 98(10): 4961-4971, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075168

RESUMO

Two experiments investigated the effect of sulfate and hydroxychloride trace minerals (TM), Zn, Cu, and Mn, in laying hens and broiler chickens. In Expt. 1, Lohmann Brown pullets (total of 1,344) at 21 wk of age were used for a 24-wk experiment. Each of the two treatments had 32 replicates with 21 hens per replicate. At 45 wk of age, three eggs per cage were randomly selected and used for internal quality assessment. In Expt. 2, Ross 308 broilers (total of 1,080) were allocated to two treatments. Each treatment had 30 replicates with 15 chicks per replicate. On day 28, after weighing, three birds were randomly selected from 15 randomly selected pens per treatment. The birds were euthanized and blood was collected for analysis for uric acid, C-reactive protein and methylmalonic acid. Samples were also taken from pectoralis muscle of each chicken and analyzed for mRNA expression of protein synthesis or hydrolysis genes. On day 35, 7 birds per pen were used for carcass evaluation. In Expt. 1, egg weight was greater (P < 0.01) in birds receiving sulfate TM from week 16 (of experiment) onwards whereas the percentage of cracked eggs was lower (P < 0.01) in hens receiving hydroxychloride TM. Percentage hen-day production tended to be greater (P < 0.10) in hens receiving hydroxychloride TM in weeks 4 to 8 only. In Expt. 2, birds receiving hydroxychloride TM had greater (P < 0.05) weight gain and tended to have greater (P < 0.10) feed intake on day 35. Expression of the gene, PSMA1, was lower (P < 0.05) whereas plasma level of uric acid and methyl malonic acid tended to be lower (P < 0.10) in birds receiving hydroxychloride TM. It was concluded that hydroxychloride TM reduced egg loss in hens at peak production and that improved growth performance response in broilers can be partly explained by reduction in proteolytic activities in the pectoralis muscle and greater resilience to oxidative stress.


Assuntos
Galinhas/fisiologia , Cloretos/metabolismo , Óvulo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Sulfatos/metabolismo , Oligoelementos/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/crescimento & desenvolvimento , Cloretos/administração & dosagem , Cloretos/análise , Cobre/administração & dosagem , Cobre/análise , Cobre/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Masculino , Manganês/administração & dosagem , Manganês/análise , Manganês/metabolismo , Óvulo/fisiologia , Sulfatos/administração & dosagem , Sulfatos/análise , Oligoelementos/administração & dosagem , Oligoelementos/análise , Zinco/administração & dosagem , Zinco/análise , Zinco/metabolismo
16.
AAPS PharmSciTech ; 20(5): 205, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31144198

RESUMO

A limitation of antibiotic treatments for P. aeruginosa (PA) chronic pulmonary infections is the reduced efficacy due to sub-therapeutic concentrations at the infection site and the development of biofilm. A novel approach to sustain ciprofloxacin (CIP) in the lungs after inhalation is to reduce its pulmonary absorption rate by its complexation with copper (CIP-Cu). This study aimed to evaluate the antimicrobial action of cationic CIP-Cu complex in PA biofilms in terms of drug concentration and time. Two PA strains, PA01 and PA14, were grown to form biofilm layers in equilibrium with planktonic cells. Static parameters such as pyoverdine production by planktonic cells, enzymatic activity within biofilms, and biofilm biomass 24 h after the addition of CIP or CIP-Cu were evaluated. Also, the kinetic effects of CIP and CIP-Cu on biofilms were evaluated by bioluminescence kinetics using transgenic strains. No differences were observed between CIP and CIP-Cu in terms of efficacy against biofilms, validating the potential of using this complex to treat PA biofilms. Interestingly, CIP concentrations slightly below the MIC value against planktonic bacteria stimulated both virulence and biofilm PA01 production. These results support the need to accurately achieve high CIP concentration in the lungs, which can be more easily achieved by pulmonary delivery of advanced CIP formulations (CIP-metal complexes or liposomal CIP) instead of the oral administration of free CIP.


Assuntos
Antibacterianos/administração & dosagem , Biofilmes/efeitos dos fármacos , Ciprofloxacino/administração & dosagem , Cobre/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/química , Biofilmes/crescimento & desenvolvimento , Ciprofloxacino/química , Cobre/química , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/fisiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-31129174

RESUMO

The importance of trace elements in ecotoxicological investigations is a well-known issue when monitoring polluted areas such as commercial harbors. Copper represents one of the most common metal contaminants, often detected in these areas as it is widely employed in various fields and has many sources of inflow in the marine environment. Pachygrapsus marmoratus is a widespread intertidal crab species that has been extensively studied in ecology, ethology and population genetics. Ecotoxicological studies have also been performed, exclusively on the adult stage. In the present study we investigated the mortality and biochemical (oxidative stress and neurotoxicity) responses of P. marmoratus larvae exposure to environmental relevant concentration of copper. Results showed dose-dependent responses in terms of larval mortality, with a calculated LC50 value of 0.5 mg/L of Cu2+. The LC50 concentration was used as the starting point for subsequent biochemical response evaluation. Results also demonstrated dose-dependent activation of antioxidant systems assuming a compensatory antioxidant activity to prevent higher cellular damage when larvae were exposed to the highest concentrations of copper. Moreover, a significant enhancement of neurotransmitter activities was observed, assuming a possible direct interaction of copper with the enzymes or an increase of free copper ion aliquot into the cells.


Assuntos
Braquiúros/efeitos dos fármacos , Cobre/toxicidade , Animais , Biomarcadores/metabolismo , Braquiúros/metabolismo , Catalase/metabolismo , Colinesterases/metabolismo , Cobre/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Glutationa Peroxidase/metabolismo , Larva/efeitos dos fármacos , Mortalidade , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testes de Toxicidade , Poluentes Químicos da Água/administração & dosagem , Poluentes Químicos da Água/toxicidade
18.
J Trace Elem Med Biol ; 54: 172-174, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109608

RESUMO

Menkes diseases (MD) is an X-linked recessive neurodegenerative disorder of copper metabolism, characterized by progressive multisystemic involvement. Death in the early childhood is usually observed in classical patients. Although a definite cure has not been established, copper replacement therapy administered parenterally may modify the severity of MD and permitted survival into adolescence. Subcutaneous copper-histidine supplementation is the current choice of therapy, and long-term administration is not desirable because of the expected nephrotoxicity. We report here the case of a 29-year-old male with MD who tolerated long-term intravenous copper therapy initiated at 2 months. Molecular analysis revealed hemizygous deletion mutation of ATP7A previously reported in classical MD. Although neurodevelopement is poor, no major event of central nervous system is observed, and he enjoys a good social life by interacting using gestures. Optimum management is unknown, and closed follow-up is mandatory for clarification of this phenotype.


Assuntos
Administração Intravenosa/métodos , Cobre/administração & dosagem , Cobre/uso terapêutico , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Adulto , Esquema de Medicação , Humanos , Masculino
19.
Can J Gastroenterol Hepatol ; 2019: 9897315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941331

RESUMO

The elevated level of copper is one of the hallmark features of cancer cells in most of the types of cancer. In the present study, this feature has been targeted to investigate if coadministration of exogenous copper (Cu+) and its chelating agent like disulfiram (DSF+) influence the antineoplastic activity of the anticancer drug, Gleevec (GLV+), in hepatocellular carcinoma (HCC)-induced rats via immunomodulation. After the treatment, the level of proinflammatory interleukins (IL-1, 2, 6, and 7), anti-inflammatory interleukin (IL-10) concomitant with transcription factors (NF-kB and TNF-a), and the apoptotic marker (cleaved PARP) was estimated. The cancer-induced group without treatment (CN+) demonstrated abnormally elevated level of all proinflammatory cytokines and transcription factors concomitant with a compromised level of cleaved PARP as compared to the control normal (CN-). The detailed histological analysis also supported the results exhibiting extensive inflammation and tissue fibrosis confirming the second stage of HCC. Cu+, DSF+, and GLV+ displayed mild improvement in most of the parameters, but the combination group GLV + Cu+ demonstrated remarkable recovery in histology and most of the parameters tended towards the CN- followed by GLV + DSF+. Therefore, the management of copper level is critical in realizing the antineoplastic activity of GLV up to its full potential in cancer treatment. These findings will help in improving chemoimmunotherapy and personalized cancer treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cobre/administração & dosagem , Mesilato de Imatinib/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/imunologia , Quelantes/administração & dosagem , Quelantes/farmacologia , Cobre/farmacologia , Citocinas/metabolismo , Dissulfiram/administração & dosagem , Dissulfiram/farmacologia , Mesilato de Imatinib/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Neoplasias Hepáticas/imunologia , Masculino , Ratos , Ratos Wistar
20.
Artigo em Inglês | MEDLINE | ID: mdl-31028930

RESUMO

Copper (Cu) and cadmium (Cd) are two kinds of abundant toxic metals in aquatic ecosystem. The present study evaluated the effects of waterborne Cu and Cd on oxidative stress responses and histological alterations in female rare minnow (Gobiocypris rarus). Fish were exposed for 7 days to: (i) control (no added Cu or Cd), (ii) waterborne Cu (39.2 µg L-1), (iii) waterborne Cd (299.6 µg L-1), and (iv) Cu and Cd in mixture (19.6 and 149.8 µg L-1, respectively). Antioxidant enzyme activities and gene mRNA abundance in fish tissues (gills, liver, and ovaries) were induced by Cu and Cd exposures, both individually and in mixture, at day 1, but an asynchronous response was observed between most enzyme activities and gene mRNA abundance following 7 days exposure. Biochemical analysis and histological observation indicated that exposure to Cu and Cd, alone and in combination, caused evident damage to lipids and tissue structure in gills, liver and ovaries. Comparing with single Cu or Cd exposure, Cu and Cd co-exposure induced greater increase in the mRNA expression of most antioxidant genes and caused more severe lesions in fish tissues, which suggested that exposure to waterborne Cu and Cd in mixture might increase their individual toxicity. Furthermore, positive relationships between nuclear factor erythroid 2-related factor (Nrf2) expression and expression of manganese superoxide dismutase (Mn-SOD) and catalase (CAT) were also observed in the present study, which suggested that Cu or/and Cd induced expression of these antioxidant genes were might through activation of Nrf2.


Assuntos
Cádmio/toxicidade , Cobre/toxicidade , Cyprinidae/fisiologia , Doenças dos Peixes/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Animais , Cádmio/administração & dosagem , Cobre/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Glutationa , Fígado/efeitos dos fármacos , Malondialdeído , Ovário/efeitos dos fármacos , Testes de Toxicidade , Poluentes Químicos da Água/administração & dosagem , Poluentes Químicos da Água/toxicidade
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