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1.
Cell Physiol Biochem ; 54(2): 180-194, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32068980

RESUMO

BACKGROUND/AIMS: Still in 1999 the first hints were published for the pharmacoresistant Cav2.3 calcium channel to be involved in the generation of epileptic seizures, as transcripts of alpha1E (Cav2.3) and alpha1G (Cav3.1) are changed in the brain of genetic absence epilepsy rats from Strasbourg (GAERS). Consecutively, the seizure susceptibility of mice lacking Cav2.3 was analyzed in great detail by using 4-aminopyridine, pentylene-tetrazol, N-methyl-D-aspartate and kainic acid to induce experimentally convulsive seizures. Further, γ-hydroxybutyrolactone was used for the induction of non-convulsive absence seizures. For all substances tested, Cav2.3-competent mice differed from their knockout counterparts in the sense that for convulsive seizures the deletion of the pharmacoresistant channel was beneficial for the outcome during experimentally induced seizures [1]. The antiepileptic drug lamotrigine reduces seizure activity in Cav2.3-competent but increases it in Cav2.3-deficient mice. In vivo, Cav2.3 must be under tight control by endogenous trace metal cations (Zn2+ and Cu2+). The dyshomeostasis of either of them, especially of Cu2+, may alter the regulation of Cav2.3 severely and its activity for Ca2+ conductance, and thus may change hippocampal and neocortical signaling to hypo- or hyperexcitation. METHODS: To investigate by telemetric EEG recordings the mechanism of generating hyperexcitation by kainate, mice were tested for their sensitivity of changes in neuronal (intracerebroventricular) concentrations of the trace metal cation Zn2+. As the blood-brain barrier limits the distribution of bioavailable Zn2+ or Cu2+ into the brain, we administered micromolar Zn2+ ions intracerebroventricularly in the presence of 1 mM histidine as carrier and compared the effects on behavior and EEG activity in both genotypes. RESULTS: Kainate seizures are more severe in Cav2.3-competent mice than in KO mice and histidine lessens seizure severity in competent but not in Cav2.3-deficient mice. Surprisingly, Zn2+ plus histidine resembles the kainate only control with more seizure severity in Cav2.3-competent than in deficient mice. CONCLUSION: Cav2.3 represents one important Zn2+-sensitive target, which is useful for modulating convulsive seizures.


Assuntos
Canais de Cálcio Tipo R/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Convulsões/tratamento farmacológico , Zinco/uso terapêutico , Animais , Canais de Cálcio Tipo R/genética , Proteínas de Transporte de Cátions/genética , Eletroencefalografia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Histidina/farmacologia , Íons/química , Ácido Caínico/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Convulsões/induzido quimicamente , Convulsões/patologia , Índice de Gravidade de Doença , Zinco/farmacologia , Ácido gama-Aminobutírico/metabolismo
2.
Life Sci ; 245: 117351, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31981629

RESUMO

AIMS: To study the specific therapeutic effect of zinc on spinal cord injury (SCI) and its specific protective mechanism. MAIN METHODS: The effects of zinc ions on neuronal cells were examined in a mouse SCI model and in vitro. In vivo, neurological function was assessed by Basso Mouse Scaleat (BMS) at 1, 3, 5, 7, 10, 14, 21, and 28 days after spinal cord injury. The number of neurons and histomorphology were observed by nissl staining and hematoxylin-eosin staining (HE). The chromatin and mitochondrial structure of neurons were detected by transmission electron microscopy (TEM). The expression of nuclear factor erythroid 2 related factor 2 (Nrf2)-related antioxidant protein and NLRP3 inflammation-related protein were detected in vivo and in vitro by western blot (WB) and immunofluorescence (IF), respectively. KEY FINDINGS: Zinc treatment promoted motor function recovery on days 3, 5, 7, 14, 21 and 28 after SCI. In addition, zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery. At the same time, zinc reduced the levels of reactive oxygen species (ROS) and malondialdehyde in spinal cord tissue after SCI, while increasing superoxide dismutase activity and glutathione peroxidase production. Zinc treatment resulted in up-regulation of Nrf2/Ho-1 levels and down-regulation of nlrp3 inflammation-associated protein expression in vitro and in vivo. SIGNIFICANCE: Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3 inflammation. Potential mechanisms may include activation of the Nrf 2/Ho-1 pathway to inhibit nlrp3 inflammation following spinal cord injury. Zinc has the potential to treat SCI.


Assuntos
Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Zinco/uso terapêutico , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Imunofluorescência , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Zinco/farmacologia
3.
JAMA ; 323(1): 35-48, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910279

RESUMO

Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. Design, Setting, and Participants: The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. Main Outcomes and Measures: The co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Results: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and Relevance: Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. Trial Registration: ClinicalTrials.gov Identifier: NCT01857310.


Assuntos
Suplementos Nutricionais , Ácido Fólico/farmacologia , Infertilidade Masculina/tratamento farmacológico , Sêmen/efeitos dos fármacos , Zinco/farmacologia , Adolescente , Adulto , Fragmentação do DNA/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Feminino , Fertilização In Vitro , Ácido Fólico/efeitos adversos , Ácido Fólico/uso terapêutico , Humanos , Nascimento Vivo , Masculino , Pessoa de Meia-Idade , Análise do Sêmen , Contagem de Espermatozoides , Falha de Tratamento , Adulto Jovem , Zinco/efeitos adversos , Zinco/uso terapêutico
4.
J Biochem Mol Toxicol ; 34(2): e22425, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31729815

RESUMO

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 µL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L16 (215 ) orthogonal design. The remaining two groups were given treatment with low and high doses of DMSA, respectively. After three weeks of intervention (ig), the optimal treatment group was identified according to its blood lead level, as well as some antioxidant indices in the blood, liver, and hippocampus. The results indicated that the combined administration of Fe, Zn, chrysanthemum flavonoids, and DMSA with low dosage had the most significant effect on increasing the activities of blood delta-aminolevulinic acid dehydratase and superoxide dismutase (SOD), hepatic SOD and hippocampus nitric oxide synthase while decreasing the blood lead level, the content of hepatic malondialdehyde and hippocampus nitric oxide; this was considered the optimal treatment group. There was no difference in the level of blood hemoglobin between the optimal treatment group and the model control group (the first group of the orthogonal experiment). The activities of blood glutathione (GSH), hepatic GSH and glutathione peroxidase of the optimal treatment group were the same as other groups', and the recovery of the related indexes in the optimal effect group closely resembled the high dosage DMSA group. It can be concluded that the coadministration of Fe, Zn, and chrysanthemum flavonoids along with a low-dose DMSA effectively reduces Pb poisoning and lead-induced oxidative damage in lead-exposed mice; the result may provide a theoretical reference for the treatment of Pb poisoning.


Assuntos
Cálcio/farmacologia , Chrysanthemum/química , Flavonoides/farmacologia , Ferro/farmacologia , Intoxicação por Chumbo/tratamento farmacológico , Extratos Vegetais/farmacologia , Succímero/farmacologia , Zinco/farmacologia , Animais , Cálcio/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Flavonoides/administração & dosagem , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ferro/administração & dosagem , Chumbo/efeitos adversos , Chumbo/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Sintase do Porfobilinogênio/sangue , Succímero/administração & dosagem , Superóxido Dismutase/sangue , Resultado do Tratamento , Zinco/administração & dosagem
5.
J Appl Microbiol ; 128(1): 202-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31536673

RESUMO

AIMS: Fibre membranes containing metals have attracted great attention because of their high antibacterial efficiency. However, comparison of antibacterial activity of fibres with multi-metals in air samples has remained understudied. METHODS AND RESULTS: Different ion exchanged nano-zeolite Y (IE-NZY) of Ag, Zn and Cu was studied. Polyvinylpyrrolidine/polyvinylidene fluoride nanofibres containing various IE-NZY were synthesized according to electrospinning technique. The presence of metal ions was confirmed using XRF. The morphological properties of nanofibres were characterized by SEM. Zone of inhibition was seen between 10·1 and 12 mm against Staphylococcus aureus and 11·5-14·57 for Escherichia coli. IE-NZY containing Ag, Zn and Cu had the highest antibacterial efficiency. In the air samples, there were any colonies on the media under the Ag/Cu-NZY and Zn/Cu/Ag-NZY nanofibres. CONCLUSIONS: The bacterial inhibition for nanofibres containing a three metal nano-zeolite Y (TM-NZY) is higher than bimetals (BM-NZY) types while for monometals nano-zeolite Y (MM-NZY), it was lower compared to the others. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicate significant antibacterial activity of ion-exchanged NZY in air sampling.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Metais/química , Zeolitas/química , Zeolitas/farmacologia , Antibacterianos/síntese química , Cobre/química , Cobre/farmacologia , Escherichia coli/efeitos dos fármacos , Metais/farmacologia , Testes de Sensibilidade Microbiana , Nanofibras/química , Nanofibras/ultraestrutura , Prata/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Zinco/química , Zinco/farmacologia
6.
J Enzyme Inhib Med Chem ; 35(1): 59-64, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31663383

RESUMO

A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against ß-class CAs, herein we report an inhibition study with this class of compounds against ß-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for ß-class over human isozymes, making them interesting leads for the development of new anti-infectives.


Assuntos
Amidas/farmacologia , Anti-Infecciosos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Compostos Organometálicos/farmacologia , Ácidos Fosfóricos/farmacologia , Amidas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Fungos/efeitos dos fármacos , Fungos/enzimologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/enzimologia , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Ácidos Fosfóricos/química , Fósforo/química , Fósforo/farmacologia , Relação Estrutura-Atividade , Zinco/química , Zinco/farmacologia
7.
Chemosphere ; 238: 124594, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445334

RESUMO

Enhancing the biodegradation efficiency of atrazine, a kind of commonly applied herbicide, has been attracted much more concern. Here, Zn2+ which has long been considered essential in adjusting cell physiological status was selected to investigate its role on the biodegradation of atrazine by Arthrobacter sp. DNS10 as well as the transmembrane transport of atrazine during the biodegradation period. The results of gas chromatography showed that the atrazine removal percentages (initial concentration was 100 mg L-1) in 0.05 mM Zn2+ and 1.0 mM Zn2+ treatments were 94.42% and 86.02% respectively at 48 h, while there was also 66.43% of atrazine left in the treatment without exogenous Zn2+ existence. The expression of atrazine chlorohydrolase gene trzN in the strain DNS10 cultured with 0.05 mM and 1.0 mM Zn2+ was 7.30- and 4.67- times respectively compared with that of the non-zinc treatment. In addition, the flow cytometry test suggests that 0.05 mM of Zn2+ could better adjust the membrane permeability of strain DNS10, meanwhile, the amount of atrazine accumulation in the strain DNS10 co-cultured with this level Zn2+ was 2.21 times of that of the strain without Zn2+. This study may facilitate a better understanding of the mechanisms that exogenous Zn2+ enhances the biodegradation of atrazine by Arthrobacter sp. DNS10.


Assuntos
Arthrobacter/metabolismo , Atrazina/análise , Herbicidas/análise , Hidrolases/biossíntese , Zinco/farmacologia , Biodegradação Ambiental/efeitos dos fármacos , Transporte Biológico/fisiologia , Hidrolases/genética , Permeabilidade/efeitos dos fármacos , Microbiologia do Solo
8.
Mol Biol (Mosk) ; 53(6): 1049-1056, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31876283

RESUMO

Zinc ions and glycosaminoglycans (GAGs) are found in amyloid deposits and are known to modulate the ß-amyloid peptide (Aß) aggregation, which is thought to be a key event in the pathogenesis of Alzheimer's disease (AD). Correlation spectroscopy was used to study how the H6R and D7H mutations of the metal-binding domain (MBD) of Aß42 affect the modulation of its zinc-induced aggregation by the model GAG heparin. The H6R mutation was shown to decrease and the D7H mutation to increase the Aß42 propensity to aggregate in the presence of zinc ions. In addition, H6R diminished and D7H enhanced the modulating effect of heparin. The difference in the heparin-dependent modulation was associated with coordination of zinc ions within the MBDs of the mutant peptides. The findings indicate that anion-binding sites formed by complexes of zinc ions with the Aß MBD play an essential role in the interaction of zinc-induced Aß aggregates with heparin.


Assuntos
Peptídeos beta-Amiloides/efeitos dos fármacos , Peptídeos beta-Amiloides/genética , Heparina/farmacologia , Mutação , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/genética , Agregação Patológica de Proteínas/genética , Zinco/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Humanos , Fragmentos de Peptídeos/química
9.
J Agric Food Chem ; 67(45): 12393-12401, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31596571

RESUMO

Accumulation of toxic copper in soil and development of copper-resistant pests are emerging challenges currently faced by the agricultural community worldwide. As an alternative, we have developed a ternary zinc chelate solution (TSOL) pesticide where zinc ions are the primary active ingredient. The material is composed of zinc, urea, and hydrogen peroxide. Urea was chosen as it is widely used as a plant fertilizer and can also bind to both zinc and hydrogen peroxide. No phytotoxicity was observed with TSOL on Meyer lemon (Citrus × meyeri) seedlings at a field spray rate of 800 µg/mL Zn metal concentration. Antimicrobial studies showed that TSOL exhibited improved killing efficacy against Escherichia coli and Xanthomonas alfalfae compared to Zn ions alone. Citrus canker field trials in a grapefruit (Chrysopelea paradisi) grove over three years showed that TSOL provided comparable disease protection to copper products at an equivalent or lower metal content.


Assuntos
Antibacterianos/química , Citrus/microbiologia , Peróxido de Hidrogênio/química , Doenças das Plantas/microbiologia , Ureia/química , Zinco/química , Zinco/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Peróxido de Hidrogênio/farmacologia , Folhas de Planta/microbiologia , Ureia/farmacologia , Xanthomonas/efeitos dos fármacos , Xanthomonas/crescimento & desenvolvimento
10.
J Appl Biomater Funct Mater ; 17(2): 2280800019857064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597509

RESUMO

BACKGROUND: Rapid corrosion rates are a major impediment to the use of magnesium alloys in bone tissue engineering despite their good mechanical properties and biodegradability. Zinc is a promising alloy element, and it is an effective grain refiner for magnesium. ß-Ca3(PO4)2 (ß-TCP) is widely used for bone regeneration because of its good biocompatibility, and it also has a similar chemical and crystal structure to human bone. METHODS: In this research, the magnesium alloy was reinforced by adding 3%Zn (wt.%) and 5%ß-TCP (wt.%) particles in order to improve the corrosion resistance and biocompatibility. Furthermore, the biomaterial was prepared through powder metallurgy technology using NH4HCO3 as space-holding particles to construct porous Mg-3%Zn/5%ß-TCP scaffolds. RESULTS: The results revealed that the magnesium-zinc phase and calcium phosphate phase were uniformly distributed in the α-magnesium matrix. Mechanical and corrosion tests indicated that the scaffolds had mechanical strengths similar to that of human bone, and their corrosion resistance decreased with an increase in the porosity. The scaffolds had cytotoxicity grades of 0-1 against MG63 cells, SaoS2 cells, and HK-2 cells, which suggested that they were appropriate for cellular applications. In addition, the scaffolds demonstrated excellent biocompatibility when tested in rabbits. CONCLUSIONS: These results indicate that porous Mg-3%Zn/5%ß-TCP scaffolds are promising biodegradable implants for bone tissue engineering.


Assuntos
Implantes Absorvíveis , Ligas , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio , Magnésio , Tecidos Suporte/química , Zinco , Ligas/química , Ligas/farmacologia , Animais , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Linhagem Celular Tumoral , Corrosão , Humanos , Magnésio/química , Magnésio/farmacologia , Porosidade , Coelhos , Engenharia Tecidual , Zinco/química , Zinco/farmacologia
11.
Fish Shellfish Immunol ; 94: 761-768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585240

RESUMO

This study was designed to evaluate the effects of zinc on inflammation and tight junction (TJ) in different intestinal regions of common carp under sub-chronic arsenic insult. Fish were exposed to zinc (0, 1 mg/L) and arsenic trioxide (0, 2.83 mg/L) in individual or combination for a month. Inflammatory infiltration and TJ structure changes were displayed by H&E staining and transmission electron microscope. To further explore these changes, biochemical indicator (SOD), gene or protein expressions of inflammatory responses (NF-κB, IL-1ß, IL-6 and IL-8) and TJ proteins (Occludin, Claudins and ZOs) were determined. In the anterior intestine, arsenic decreased activity of SOD, mRNA levels of Occludin, Claudins and ZOs, increased mRNA levels of ILs. However, unlike the anterior intestine, arsenic has an upregulation effects of Occludin and Claudin-4 in the mid intestine. These anomalies induced by arsenic, except IL-8, were completely or partially recovered by zinc co-administration. Furthermore, transcription factor (NF-κB) nuclear translocation paralleled with its downstream genes in both intestinal regions. In conclusion, our results unambiguously suggested that under arsenic stress, zinc can partly relieve intestinal inflammation and disruption of tight junction segment-dependently.


Assuntos
Arsênico/efeitos adversos , Carpas , Enterotoxinas/efeitos adversos , Doenças dos Peixes/prevenção & controle , Intestinos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Zinco/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças dos Peixes/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Inflamação/veterinária , Intestinos/fisiologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/fisiologia
12.
Chemosphere ; 236: 124869, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549675

RESUMO

Chronic arsenicosis has threatened the survival of aquatic animals with molecular mechanisms yet clear. In the present study, liver damage was evident by fluctuated activities of transaminases and declined ATPases in common carp under arsenic (As) exposure for 30 days. Mechanically, As significantly decreased cytochrome P-1A (CYP1A) activity and increased reactive oxygen species (ROS) content, which corroborated mitochondrial dysfunction in the hepatocytes. This hypothesis was further suggested by Caspase-3-executed apoptosis by death receptor pathway (Fas, TNF-α and Caspase-8) and mitochondrial pathway (Bax, Bcl-2 and Caspase-9). The above results indicated that As-elicited oxidative damage lead to apoptotic hepatic injury in carp. On the contrary, zinc (Zn) exerted an ROS scavenger and an antidote to As in the present model evidenced by alleviated liver injury and restored liver function index. Moreover, Zn and As co-administration displayed partially recovered CYPs enzyme system and quenched apoptotic positive cells compared As treated alone. These outcomes could be applied to develop counter practices based on Zn preparations to decrease the biotoxicity of As.


Assuntos
Apoptose/efeitos dos fármacos , Arsenitos/toxicidade , Carpas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Zinco/farmacologia , Animais , Caspase 3 , Caspase 9 , Hepatócitos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , Poluentes Químicos da Água/metabolismo , Zinco/metabolismo
13.
Dokl Biochem Biophys ; 487(1): 264-268, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559594

RESUMO

We studied the effect of zinc excess (1000 µM) and low positive temperature (4°C) on the IRT1 gene expression in barley roots and leaves. Exposure at each of the stress factors separately induced an increase in the content of the HvIRT1 gene transcripts, which was more pronounced in leaves. At the same time, the growth of seedlings continued. Under the combined action of the stress factors in the first 3 days, the amount of mRNA also increased, but after 7 days of exposure it significantly declined, which correlated with the complete inhibition of seedling growth. It is assumed that the seedling growth inhibition under the combined effect of zinc excess and low temperature is associated with a decrease in the transcriptional activity of the HvIRT1 gene, due to the deficiency in a number of trace elements under these conditions.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Hordeum/genética , Folhas de Planta/efeitos dos fármacos , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Temperatura Ambiente , Zinco/farmacologia , Relação Dose-Resposta a Droga , Hordeum/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo
14.
Mater Sci Eng C Mater Biol Appl ; 105: 110084, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546418

RESUMO

Spinel ferrite-based nanoparticles are being widely applied in bone tissue regeneration because of their outstanding properties such as their capability to be applied in hyperthermia-based bone cancer therapy. In the present study, Cu0.3Zn0.2Mg0.5Fe2O4 nanoparticles are synthesized through thermal-treatment method followed by calcination at 650 °C. The calcined nanoparticles are characterized through X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM) equipped with energy dispersive spectroscopy (EDS) and elemental mapping, Fourier transform infrared spectroscopy (FTIR), and vibrating sample magnetometer (VSM). Then from the nanoparticles, a disk is fabricated and sintered at 800 °C to assess Cu0.3Zn0.2Mg0.5Fe2O4 basic requirements of a bone substitute like apatite-formation ability, degradation, mechanical properties, and cell compatibility and so compressive strength, apatite forming ability up to 21 days in simulated body fluid (SBF), in vitro degradation in two different buffers, antibacterial activity, cell compatibility, and attachment are assessed in vitro. The results show that the magnetization saturation (Ms) is increased from 52 to 60 emu/g when the nanoparticles are sintered at 800 °C. Immersion the disk into SBF is synchronized with deposition of spherical CaP particles on the surface of disk and the XRD after soaking period proves that the depositions are hydroxyapatite. The degradability of disk is assessed into phosphate buffer saline (PBS) and citric acid buffer (CAB) up to 21 days. A gram-positive and a gram-negative bacteria are used to assess the disk's antibacterial activity and the disk exhibits acceptable activity against both of them. The cell compatibility and attachment of disk in the exposure of MG63 cell line are assessed up to 7 days and the results prove high cell compatibility of the disk.


Assuntos
Óxido de Alumínio , Regeneração Óssea/efeitos dos fármacos , Cobre , Compostos Férricos , Óxido de Magnésio , Magnésio , Nanopartículas Metálicas/química , Zinco , Óxido de Alumínio/química , Óxido de Alumínio/farmacologia , Animais , Linhagem Celular Tumoral , Cobre/química , Cobre/farmacologia , Durapatita/metabolismo , Compostos Férricos/química , Compostos Férricos/farmacologia , Magnésio/química , Magnésio/farmacologia , Óxido de Magnésio/química , Óxido de Magnésio/farmacologia , Camundongos , Zinco/química , Zinco/farmacologia
15.
Mater Sci Eng C Mater Biol Appl ; 105: 110065, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546449

RESUMO

In order to investigate the influence of Zn on the hydration reaction of calcium phosphate cement (CPC), the incompletely hydrated CPC tablets were kept soaking in varying zinc-containing tris-(hydroxymethyl)-aminomethane/hydrochloric acid (Zn-Tris-HCl) buffers. It was found that Zn could retard the CPC hydration, the inhibitory effect was in direct proportional to the Zn content in the Zn-Tris-HCl buffer, and overhigh concentration of Zn (≧800 µM) caused the CPC hydration products having different phase composition and surface morphology. Cell culture experimental results revealed the CPC tablets which were soaked in the Zn-Tris-HCl buffer containing relative low Zn content (≦320 µM) favored the mouse bone mesenchymal stem cells (mBMSCs) spreading. When Zn-doped CPC tablets released 10.91 to 27.15 µM of zinc ions into the cell culture medium, it greatly contributed to the improvement of the proliferation ability and the alkaline phosphatase (ALP) activity of the mBMSCs. In the same case, the expression of osteogenesis related genes such as collagen I and runt-related transcription factor 2 was remarkably up-regulated as well. However, the release of high concentration of Zn (128.58 µM) would significantly reduce the ALP activity of the mBMSCs. Therefore, Zn not only facilitates osteogenesis but also affects the CPC hydration behavior, and the CPC with suitable Zn dosage concentration has great potentials to be used for clinical bone repairing.


Assuntos
Cimentos para Ossos , Células da Medula Óssea/metabolismo , Fosfatos de Cálcio , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Zinco , Animais , Cimentos para Ossos/química , Cimentos para Ossos/farmacologia , Células da Medula Óssea/citologia , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Camundongos , Zinco/química , Zinco/farmacologia
16.
Mater Sci Eng C Mater Biol Appl ; 104: 109910, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500031

RESUMO

Novel bioactive glasses with different amount of zinc oxide (ZnO), namely 2, 3.8 and 5 mol%, were designed, produced by a melt-quenching route and investigated in terms of biological performance. Proper amounts of ZnO were added to a previously developed bioactive glass containing strontium and magnesium, characterized by an ultra-high crystallization temperature. Thus, the aim of the work was to obtain a bioactive glass with high crystallization temperature in view of an eventual thermal treatment, as well as antibacterial properties (due to the antimicrobial effect of zinc, as reported in the literature). Bioactivity was investigated by immersion in Simulated Body Fluid (SBF), which is a commonly used protocol to evaluate samples' bioactivity in vitro. Additionally, in order to exclude the possible cytotoxicity of Zn containing bioactive glasses, a biological investigation using MLO-Y4 cells was carried out, both by direct (NR uptake) and indirect (MTT) contact tests. Finally, the antibacterial effects of the produced bioactive glasses against Staphylococcus epidermidis (Gram-positive), Pseudomonas aeruginosa and Escherichia coli (both Gram-negative) were investigated.


Assuntos
Antibacterianos/farmacologia , Vidro/química , Temperatura Ambiente , Zinco/farmacologia , Animais , Bactérias/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Forma Celular/efeitos dos fármacos , Cristalização , Camundongos , Testes de Sensibilidade Microbiana , Difração de Raios X
17.
Environ Pollut ; 254(Pt B): 113086, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479812

RESUMO

Previous studies have shown the effect of surface coatings on biofouling; however, they did not take into account the interaction of the micro and macrofouling communities, the effect of substrate orientation and the zooplankton-zoobenthic coupling together. Therefore, the aim of this study was to evaluate the effect of Zn- and Cu2O-based coatings on micro and macrofouling on steel surfaces, while also observing the role of substrate orientation and zooplankton supply. An experiment was carried out in the Patos Lagoon Estuary in southern Brazil for three months between spring and summer, where ASTM-36 steel plates represented different coatings (Zn- and/or Cu2O-based) and orientations (vertical and horizontal). To assess the zooplankton supply, sampling was carried out weekly using a 200 µm plankton net. Zn-based coating positively affected microfouling density compared to uncoated surfaces. The same pattern was observed with macrofouling, associated with vagile fauna preference, which represented 70% of the settled macrofoulers. Cu2O-based antifouling painted surfaces showed the highest microfouling density inhibition, while Zn + Cu2O-based coating did not affect the bacteria adhesion but showed lower density compared to Zn-based coating alone. The coatings combination showed the highest invertebrate inhibition. In this way, the macrofouling community was more sensitive than microfouling was to the antifouling coatings tested. The substrate orientation only affected macrofouling, horizontal surfaces being more attractive than vertical. Meroplankton, tychoplankton and holoplankton were recorded on the surfaces, although their representation in plankton was not proportional to the recruits recorded on the substrates. This was probably due to fast dispersion, the interactions of other factors and/or ecological succession stage. Surface coating, substrate orientation, and zooplankton supply interacted with the biofouling process on steel in different ways depending on the organism evaluated. Therefore, copper oxide- and zinc-based coatings were not suitable as coatings to avoid the total biofouling establishment.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Incrustação Biológica/prevenção & controle , Aço/análise , Zinco/farmacologia , Bactérias/efeitos dos fármacos , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Brasil , Cobre/química , Cobre/farmacologia , Pintura/análise , Zinco/química
18.
Nutrients ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484386

RESUMO

During recent years, we have witnessed a growing appreciation of several micronutrients in the immune response, including vitamins and minerals [...].


Assuntos
Homeostase/fisiologia , Inflamação/metabolismo , Oligoelementos/farmacologia , Zinco/farmacologia , Humanos , Oligoelementos/metabolismo , Zinco/metabolismo
19.
J Appl Microbiol ; 127(6): 1741-1750, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31487417

RESUMO

AIMS: Lactic acid is a natural antimicrobial in food industry, and also exists in fermented food. It was reported that sublethally injured Escherichia coli could survive in acidic conditions. When conditions become advantageous, injured E. coli can restore physiological function, which is a potential threat in food industry. Recovery is a necessary step for discriminating injured bacteria, but the resuscitation mechanism of injured bacteria is still unknown. METHODS AND RESULTS: In our study, sublethal lactic acid treatment (pH 4·2, 60 min) posed oxidative stress on E. coli by decrease of superoxide dismutase (SOD) activity and overproduction of reactive oxygen species (ROS). Zinc with low concentration (1·0 mmol l-1 ) significantly increased the recovery ratio of injured E.coli induced by lactic acid. The recovery ratios of injured cell in minimal A medium (minA) with 1·0 mmol l-1 zinc reached to that with 3·0 mmol l-1 catalase (CAT). Conversely, the addition of zinc chelator N, N, N', N'-tetrakis (2-pyridylmethyl) decreased the recovery ratio. Zinc accelerated resuscitation of injured E. coli by improving SOD activity, and decreasing ROS production. Deletion of sodC encoding Cu/ZnSOD, katE/katG encoding CAT or regulating gene rpoS significantly decreased the recovery ratio. Among all of the mutants in this study, ΔrpoS and ΔsodC showed the lowest recovery ratio, which means they played significant roles in the process of resuscitation. CONCLUSION: We provided direct evidence that zinc mediated resuscitation of lactic acid-injured E. coli by relieving oxidative stress. Zinc can be used as a low-cost and effective agent to improve recovery ratio and detection efficiency of injured bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibacterial agents are a challenge for bacteria, but bacteria can survive as a sublethally injured state under stresses. Using injured E. coli induced by lactic acid as a model organism, we validated the significant role of zinc on resuscitation of injured cells.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Ácido Láctico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Zinco/farmacologia , Catalase/genética , Catalase/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Escherichia coli/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
20.
Eur J Med Chem ; 182: 111672, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505452

RESUMO

Based on the unique role of a common unit in a family of sulfur-containing natural histone deacetylases (HDACs) inhibitors, we have chosen largazole as an example of these inhibitors and adopted a "fluorine scan" strategy towards modification of this common unit. Thus a set of fluoro largazole analogues has been designed, synthesized and evaluated in enzymatic as well as cellular assays. The preliminary results indicate that introduction of fluorine at the various position of the unit has an important impact on the activity and selectivity of HDACs. Unlike other modifications which often led to significant reduction or complete loss of activity as reported in the literature, most of these fluoro thiols have displayed comparable or enhanced activity and selectivity in enzymatic assays. Two of the sulfhydryl esters have also exhibited excellent inhibitory activity in cellular assays with a few selected cell lines. The C19-fluorinated analogue has been further studied by immunoblot analysis, confirming that it is a potent selective class I HDAC inhibitor and supporting that the potent cellular antiproliferative activity is due to HDAC inhibition. The molecular docking study reveals that introducing fluorine at the C19 position does not change the original interactions, but might have made a subtle change in binding conformation, resulting in an obvious improvement in activity.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Compostos Organometálicos/farmacologia , Compostos de Sulfidrila/farmacologia , Zinco/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade , Compostos de Sulfidrila/química , Zinco/química
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