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1.
J Agric Food Chem ; 68(10): 2973-3005, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32105058

RESUMO

Leaf teas are widely used as a purported treatment for dysregulated glucose homeostasis. The objective of this study was to systematically evaluate the clinical and cellular-metabolic evidence, published between January 2013 and May 2019, and indexed on PubMed, ScienceDirect, and Web of Science, supporting the use of leaf teas for this purpose. Fourteen randomized controlled trials (RCTs) (13 on Camellia sinensis teas) were included, with mixed results, and providing scant mechanistic information. In contrast, 74 animal and cell culture studies focusing on the pancreas, liver, muscle, and adipose tissue yielded mostly positive results and highlighted enhanced insulin signaling as a recurring target associated with the effects of teas on glucose metabolism. We conclude that more studies, including RCTs and pre-clinical studies examining teas from a wider variety of species beyond C. sinensis, are required to establish a stronger evidence base on the use of leaf teas to normalize glucose metabolism.


Assuntos
Camellia sinensis/química , Glucose/metabolismo , Extratos Vegetais/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Zoolog Sci ; 37(1): 50-60, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32068374

RESUMO

The labial palps of bivalves are thought to be involved in suspension feeding. However, the function of their muscular movements and neural regulation are still unclear. In semi-intact preparations of Mytilus, in which one valve was removed, suspended particles were removed from the labial palps following two kinds of compound movements: torsional and rotational. Both of these compound movements are therefore thought to function in rejection during feeding. These movements were observed in reduced preparations of isolated labial palps with intact cerebral ganglia, and were maintained even after removal of the cerebral ganglia, suggesting that they are generated by the peripheral neural network. Stimulation of the anterior pallial nerve elicited tetanic contraction of the labial palp, followed by secondary responses, including torsional movement. Secondary responses were dramatically reduced by a high concentration of divalent cations, in which polysynaptic pathways were inhibited. Hence, the cerebral ganglia may play an excitatory role within the peripheral neural network and the labial palp musculature via the anterior pallial nerve. Administration of serotonin induced repetitive muscular movements, whereas dopamine did not induce muscular movements. Serotonin-induced muscular movements were not elicited under a high concentration of divalent cation condition. In histochemical experiments, both the serotonergic and dopaminergic neural processes and cell body-like structures were widely observed inside the labial palp, the anterior pallial nerve, and the cerebral ganglia. Serotonin may thus contribute to activation of polysynaptic peripheral pathways, which are involved in regulating compound movements.


Assuntos
Comportamento Alimentar , Músculos/inervação , Mytilus/fisiologia , Animais , Dopamina/farmacologia , Gânglios , Movimento/efeitos dos fármacos , Músculos/efeitos dos fármacos , Serotonina/farmacologia
3.
J Orthop Res ; 38(2): 329-335, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31531986

RESUMO

The recommended treatment varies depending on the severity of muscle injuries. The aim of this study was to evaluate the in vitro myoblast proliferation and the in vivo histologic and physiologic effects of hyperbaric oxygen treatment on muscle healing after contusion. Cells from the C2C12 myoblast cell line were exposed to 100% O2 for 25 min then to air for 5 min at 2.5 atmospheres absolute in a hyperbaric chamber for a total treatment duration of 90 min per 48 h at intervals of 2, 4, 6 and 8 days. Cell growth measurements and western blot analysis of myogenin and actin were performed. Then, 18 mice aged 8-10 weeks were used in the muscle contusion model. The histologic and physiologic effects and muscle regeneration after hyperbaric oxygen treatment were evaluated. The myoblast growth rate was significantly higher (p < 0.05) after hyperbaric oxygen treatment. Densitometric evaluation demonstrated a 39% (p < 0.05) and 25% (p < 0.05) increase in myogenin and actin protein levels, respectively, in the cells treated with 1 dose of hyperbaric oxygen. Similarly, the myogenin and actin protein levels increased for samples receiving multiple hyperbaric oxygen treatments when compared with the control. Physiologic evaluation of fast twitch and tetanus strength revealed a significant difference between the control group and the 14-day hyperbaric oxygen group. In conclusion, hyperbaric oxygen treatment increases the myoblast growth rate and myogenin and actin production. Better histologic and physiologic performance were found after hyperbaric oxygen treatment in animal contusion model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:329-335, 2020.


Assuntos
Contusões/terapia , Oxigenação Hiperbárica , Mioblastos/efeitos dos fármacos , Oxigênio/uso terapêutico , Actinas/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Contusões/patologia , Camundongos , Força Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/patologia , Miogenina/metabolismo , Oxigênio/farmacologia , Regeneração/efeitos dos fármacos
5.
Aquat Toxicol ; 218: 105373, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786386

RESUMO

Production of industrial effluents have led to increased copper (Cu) pollution of aquatic ecosystems, impacting the physiology of aquatic vertebrates. Past work has shown that Cu exerts its toxicity by disruption ion regulation and/ or increasing oxidative stress. However, it remains unclear how Cu may influence aerobic metabolism and hypoxia tolerance, two possible targets of its toxicity. To address this issue, we exposed freshwater acclimated killifish (F. heteroclitus) to a 96 h Cu exposure at a target concentration of 100 µg L-1. We determined resting oxygen consumption (MO2), MO2max after exhaustive exercise, and followed MO2 for 3 h in post-exercise recovery in water with either no Cu or 100 µg L-1 Cu. We assessed hypoxia tolerance by determining the critical oxygen tension (Pcrit). It was found that killifish exposed to combined 96 h Cu exposure and Cu present during metabolic measurements, showed a significant decrease in MO2max and in aerobic scope (MO2max - MO2rest), compared to control fish. However, changes in blood and muscle lactate and muscle glycogen were not consistent with an upregulation of anaerobic metabolism as compensation for reduced aerobic performance in Cu exposed fish. Hypoxia tolerance was not influenced by the 96 h Cu exposure or by presence or absence of Cu during the Pcrit test. This study suggests that Cu differentially influences responses to changes in oxygen demand and oxygen availability.


Assuntos
Aclimatação/efeitos dos fármacos , Cobre/toxicidade , Fundulidae/metabolismo , Hipóxia/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Anaerobiose , Animais , Ecossistema , Água Doce/química , Fundulidae/sangue , Fundulidae/fisiologia , Glicogênio/metabolismo , Ácido Láctico/sangue , Músculos/efeitos dos fármacos , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Esforço Físico/fisiologia
6.
J Sci Food Agric ; 100(1): 119-128, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31441054

RESUMO

BACKGROUND: T-2 toxin (T-2) is a potent mycotoxin and a common contaminant of aquatic animal feed, posing a serious risk to health and aquatic animals. We investigated the effect of T-2 on shrimp muscle proteins using proteomics and conventional biochemical methods. Shrimp were fed a diet containing T-2 at 0-12.2 mg kg-1 for 20 days, and changes to the muscle protein composition, ATPase activities, and the sulfhydryl (SH) content and hydrophobicity of actomyosin (AM) were determined. A proteomics study of the proteins was conducted with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional (2D) electrophoresis, and matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF/TOF MS). RESULTS: Exposure to T-2 markedly affected the muscle protein composition of shrimp in a concentration-responsive manner that displayed a diphasic effect. At a low T-2 concentration (1.2 mg kg-1 ), the levels of three major muscle proteins (myofibrillar, sarcoplasmic, and stroma) increased but at higher concentrations they declined progressively. T-2 exposure also led to a breakdown of muscle proteins as evidenced by increases in alkali-soluble protein and the surface hydrophobicity (SoANS) of AM. Thirty differentially expressed proteins were detected, 12 of which showed a concentration-response relationship with T-2 exposure. Among them, 11 homologous proteins were identified by mass spectrometry (MS), with several being key enzymes in energy metabolism. CONCLUSION: This study demonstrated that T-2 exposure at medium to high concentrations could significantly affect the protein composition and quality of shrimp muscle, and potentially some of its key metabolisms. One of the arginine kinases (spot 27) was particularly responsive to T-2 and could potentially be used as a biomarker protein for T-2 intoxication by shrimp. © 2019 Society of Chemical Industry.


Assuntos
Proteínas Musculares/química , Penaeidae/efeitos dos fármacos , Frutos do Mar/análise , Toxina T-2/toxicidade , Ração Animal/análise , Animais , Eletroforese em Gel de Poliacrilamida , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculos/química , Músculos/efeitos dos fármacos , Músculos/metabolismo , Penaeidae/química , Penaeidae/genética , Penaeidae/metabolismo , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
Mar Pollut Bull ; 143: 101-108, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31789143

RESUMO

This is the first report to assay the heavy metal accumulation in Blue Swimmer Crab in the northern Bay of Bengal. The present study finds that copper (Cu) concentration though has been the highest compared to the other metals, particularly in the gill. Cadmium (Cd) and lead (Pb) have high affinity to be concentrated in Hepatopancreas all through the year. All the metal concentrations were higher during monsoon season (comparatively low salinity) than non-monsoon (high salinity) in the different body parts of Blue swimmer crab i.e. the inverse relationship between accumulation of heavy metals and sea water salinity has been shown. Present study revealed that salinity having the role to accumulate metal in different body parts of Blue Swimmer Crab. In future, microcosm experiments should be done to test the effect of frequent fluctuations of ambient salinity, such as is usual in different seasons in the present study area.


Assuntos
Metais Pesados/farmacocinética , Água do Mar/química , Poluentes Químicos da Água/farmacocinética , Animais , Baías , Braquiúros/efeitos dos fármacos , Braquiúros/metabolismo , Brânquias/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hepatopâncreas/química , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Índia , Metais Pesados/análise , Músculos/química , Músculos/efeitos dos fármacos , Músculos/metabolismo , Salinidade , Estações do Ano , Distribuição Tecidual , Poluentes Químicos da Água/análise
9.
Ecotoxicol Environ Saf ; 186: 109753, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604159

RESUMO

Nitrite is a common toxic substance in culture systems of Litopenaeus vannamei, and the stress may disturb hemocyanin synthesis and energy metabolism and result in shrimp death. In the present study, nitrite at concentrations of 0 (control), 3.3 (46.2 NO2-N mg/L), 6.6 (92.4) and 9.9 mM (138.6) was used to evaluate the responses of hemocyanin level and energy metabolism in L. vannamei (5.80 ±â€¯0.44 cm, 1.88 ±â€¯0.38 g) for 96 h. The mortality rate at 96 h increased with nitrite concentration (50% at 9.9 mM, 40% at 6.6 mM, 30% at 3.3 mM, and 10% at 0 mM). In general, HIF-1α and hemocyanin mRNA expression in the nitrite stress groups was upregulated from 6 to 12 h and downregulated from 24 to 96 h. In the hemolymph, nitrite levels were significantly elevated in a dose-dependent manner, and exposure to nitrite stress significantly decreased the oxyhemocyanin content from 24 to 96 h. The glucose and lactate levels in the hemolymph in the nitrite stress groups were higher than those in the control group from 12 to 96 h. Compared with the control group, the shrimp in the nitrite stress groups exhibited decreased glycogen concentrations in the hepatopancreas. The triglyceride (TG) levels in the nitrite stress groups were all higher than those in the control group from 48 to 96 h. The hexokinase (HK) activity in the hepatopancreas and muscle increased in the nitrite stress groups from 48 to 96 h. In general, nitrite stress enhanced the activities of pyruvate kinase (PK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) in muscle from 24 to 96 h. In addition, nitrite stress decreased the activities of succinate dehydrogenase (SDH) and fatty acid synthase (FAS) from 24 to 96 h in the hepatopancreas and muscle. This study indicates that exposure to nitrite stress can enhance the accumulation of nitrite in the hemolymph and then reduce oxygenation and hemocyanin synthesis, leading to tissue hypoxia and thereby resulting in accelerated anaerobic metabolism and the inhibition of aerobic metabolism. The effects of nitrite stress on hemocyanin synthesis and energy metabolism may be one of the reasons for the mortality of L. vannamei in culture systems.


Assuntos
Anaerobiose/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hemocianinas/metabolismo , Nitritos/toxicidade , Oxigênio/metabolismo , Penaeidae/efeitos dos fármacos , Estresse Fisiológico , Animais , Aquicultura , Glicogênio/metabolismo , Hemolinfa/efeitos dos fármacos , Hemolinfa/metabolismo , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Penaeidae/crescimento & desenvolvimento , Penaeidae/metabolismo , Alimentos Marinhos , Triglicerídeos/metabolismo
10.
Biomed Pharmacother ; 119: 109416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518878

RESUMO

Atorvastatin and its lactone form metabolite are reported to be associated with statin-induced myopathy (SIM) such as myalgia and life-threatening rhabdomyolysis. Though the statin-induced rhabdomyolysis is not common during statin therapy, its incidence will significantly increase due to pharmacokinetic drug-drug interactions (DDIs) with inhibitor drugs which inhibit atorvastatin's and its lactone's metabolism and hepatic uptake. Thus, the quantitative analysis of DDIs of atorvastatin and its lactone with cytochrome P450 3A4 (CYP3A4) and organic anion-transporting polypeptide (OATP) inhibitors is of great importance. This study aimed to predict pharmacokinetic DDIs possibly causing atorvastatin-induced rhabdomyolysis using Physiologically Based Pharmacokinetic (PBPK) Modelling. Firstly, we refined the PBPK models of atorvastatin and atorvastatin lactone for predicting the DDIs with CYP3A4 and OATP inhibitors. Thereafter, we predicted the exposure changes of atorvastatin and atorvastatin lactone originating from the case reports of atorvastatin-induced rhabdomyolysis using the refined models. The simulation results show that pharmacokinetic DDIs of atorvastatin and its lactone with fluconazole, palbociclib diltiazem and cyclosporine are significant. Consequently, clinicians should be aware of necessary dose adjustment of atorvastatin being used with these four inhibitor drugs.


Assuntos
Atorvastatina/efeitos adversos , Atorvastatina/farmacocinética , Modelos Biológicos , Rabdomiólise/induzido quimicamente , Idoso , Atorvastatina/sangue , Atorvastatina/química , Simulação por Computador , Interações de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/efeitos dos fármacos , Músculos/patologia
11.
PLoS Pathog ; 15(9): e1008041, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31553770

RESUMO

Filariae are parasitic nematodes that are transmitted to their definitive host as third-stage larvae by arthropod vectors like mosquitoes. Filariae cause diseases including: lymphatic filariasis with distressing and disturbing symptoms like elephantiasis; and river blindness. Filarial diseases affect millions of people in 73 countries throughout the topics and sub-tropics. The drugs available for mass drug administration, (ivermectin, albendazole and diethylcarbamazine), are ineffective against adult filariae (macrofilariae) at the registered dosing regimen; this generates a real and urgent need to identify effective macrofilaricides. Emodepside, a veterinary anthelmintic registered for treatment of nematode infections in cats and dogs, is reported to have macrofilaricidal effects. Here, we explore the mode of action of emodepside using adult Brugia malayi, one of the species that causes lymphatic filariasis. Whole-parasite motility measurement with Worminator and patch-clamp of single muscle cells show that emodepside potently inhibits motility by activating voltage-gated potassium channels and that the male is more sensitive than the female. RNAi knock down suggests that emodepside targets SLO-1 K channels. We expressed slo-1 isoforms, with alternatively spliced exons at the RCK1 (Regulator of Conductance of Potassium) domain, heterologously in Xenopus laevis oocytes. We discovered that the slo-1f isoform, found in muscles of males, is more sensitive to emodepside than the slo-1a isoform found in muscles of females; and selective RNAi of the slo-1a isoform in female worms increased emodepside potency. In Onchocerca volvulus, that causes river blindness, we found two isoforms in adult females with homology to Bma-SLO-1A and Bma-SLO-1F at the RCK1 domain. In silico modeling identified an emodepside binding pocket in the same RCK1 region of different species of filaria that is affected by these splice variations. Our observations show that emodepside has potent macrofilaricidal effects and alternative splicing in the RCK1 binding pocket affects potency. Therefore, the evaluation of potential sex-dependent effects of an anthelmintic compound is of importance to prevent any under-dosing of one or the other gender of nematodes once given to patients.


Assuntos
Brugia Malayi/efeitos dos fármacos , Brugia Malayi/fisiologia , Depsipeptídeos/farmacologia , Filaricidas/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Brugia Malayi/genética , Feminino , Filariose/tratamento farmacológico , Filariose/parasitologia , Técnicas de Silenciamento de Genes , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Alta/química , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Modelos Moleculares , Movimento/efeitos dos fármacos , Movimento/fisiologia , Músculos/efeitos dos fármacos , Músculos/fisiologia , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Homologia de Sequência de Aminoácidos , Fatores Sexuais
12.
Mater Sci Eng C Mater Biol Appl ; 104: 109934, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500061

RESUMO

Recently, a novel 3D titanium-mesh scaffold with bone grafting material has been proposed to reconstruct the large defect of mandible. However, how to design and optimize the 3D scaffolds of mandible is still unclear. Therefore, the aim of this study was to investigate the optimization of 3D scaffolds for mandibular defect. Both the biomechanical behavior and mechanobiological property of scaffolds were considered in this study. Four configurations (regular hexahedron, cuboctahedron, regular dodecahedron, and diamond) and three strut diameters (0.2 mm, 0.5 mm and 0.8 mm) were divided into 12 groups. By employing Finite Element Analysis and bone "Mechnostat" theory, the optimal unit cell was selected from 12 scaffolds. Then, the original implant for mandible defects was designed with the optimal unit cell, and the final implant was optimized to promote osteogenesis and avoid mechanical failure under bi-lateral chewing bite (200N) and maximum force (worse-case) bite (800 N). The results illustrated a strong correlation between the configurations and the load transmission capacity, while mechanical failure highly depended on strut size and architecture. Regular dodecahedron with a strut diameter of 0.8 mm provided a good load transfer to bone tissue while resisting the mechanical failure. Ultimately, the optimized implant was constructed with regular dodecahedron unit cell, and the strut diameters of scaffold gradually varied according to the biomechanical analysis. The computational results indicated that the optimized implant can provide an excellent mechanical environment for bone regeneration, thus achieving a long-term stability and occlusal reconstruction with dental implant. This study is expected to provide a scientific basis for the design and optimization of 3D mesh scaffolds to reconstruct a mandibular functionally and aesthetically.


Assuntos
Simulação por Computador , Implantes Dentários , Mandíbula/cirurgia , Telas Cirúrgicas , Titânio/farmacologia , Remodelação Óssea/efeitos dos fármacos , Análise de Elementos Finitos , Humanos , Músculos/efeitos dos fármacos , Porosidade , Estresse Mecânico , Tecidos Suporte/química
13.
Aquat Toxicol ; 215: 105287, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491706

RESUMO

Gold nanoparticles are used as drug delivery vectors based on the assumption that they have low toxicity. Literature has, however, produced conflicting results over the last few years. As such, this study aimed to investigate the toxicological effects of nanogold (nAu) on several indicators that range from subcellular to whole-organism level. Gene regulation, changes in oxidative stress biomarkers and swimming performance were assessed in Danio rerio (zebrafish) following exposures to nAu. Adult zebrafish were exposed in vivo to nAu for 96 h and swimming performance measured post-exposure. Liver tissue was collected for DNA microarray and Real-Time Polymerase Chain Reactions (RT-PCR) analyses to determine changes in gene expression (catalase, superoxide dismutase and metallothioneins) and protein biomarker analyses (catalase, superoxide dismutase, acetylcholine esterase, malondialdehyde, cellular energy allocation and metallothionein) were performed on whole-body samples. Swimming behaviour was assessed in 1.1 L Tecniplast™ tanks for a period of six hours and videos were analysed using Noldus EthoVision software. Critical swimming speed was measured in a Loligo® swimming tunnel. The DNA microarray revealed that fish exposed to 20 mg/L differed most from the control group. At 20 mg/L there was a significant increase in gene expression for all genes analysed but this didn't translate to significant responses in protein biomarker levels except for an increase in protein carbonyl formation. The behaviour results demonstrated significant changes in distance moved, swimming speed, acceleration bouts, zone alterations and time spent within the top zone - responses that are usually observed in fish responding to toxicological stress. Furthermore, the critical swimming speed of exposed fish was decreased significantly compared to the control. Since swimming performance and social interaction among zebrafish is essential to their survival, whole-organism behaviour that suggests a toxicological response after exposure to nAu is in agreement with the genetic responses measured in this study.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Peixe-Zebra/fisiologia , Animais , Biomarcadores/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Nanopartículas Metálicas/ultraestrutura , Família Multigênica , Músculos/efeitos dos fármacos , Natação , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
14.
Environ Sci Pollut Res Int ; 26(29): 30508-30523, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463743

RESUMO

The presence of natural organic matter such as humic acid (HA) can influence the behavior of graphene oxide (GO) in the aquatic environment. In this study, zebrafish embryos were analyzed after 5 and 7 days of exposure to GO (100 mg L-1) and HA (20 mg L-1) alone or together. The results indicated that, regardless of the presence of HA, larvae exposed to GO for 5 days showed an increase in locomotor activity, reduction in the yolk sac size, and total length and inhibition of AChE activity, but there was no difference in enzyme expression. The statistical analysis indicated that the reductions in total larval length, yolk sac size, and AChE activity in larvae exposed to GO persisted in relation to the control group, but there was a recovery of these parameters in groups also exposed to HA. Larvae exposed to GO for 7 days did not show significant differences in locomotor activity, but the RT-PCR gene expression analysis evidenced an increase in the AChE expression. Since the embryos exposed to GO showed a reduction in overall length, they were submitted to confocal microscopy and their muscle tissue configuration investigated. No changes were observed in the muscle tissue. The results indicated that HA is associated with the toxicity risk modulation by GO and that some compensatory homeostasis mechanisms may be involved in the developmental effects observed in zebrafish.


Assuntos
Grafite/toxicidade , Larva/efeitos dos fármacos , Peixe-Zebra/embriologia , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Ecotoxicologia , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Grafite/química , Substâncias Húmicas , Larva/fisiologia , Locomoção/efeitos dos fármacos , Mortalidade , Músculos/citologia , Músculos/efeitos dos fármacos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
15.
Environ Sci Pollut Res Int ; 26(30): 31198-31206, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463750

RESUMO

The literature indicates that exotic species have a greater tolerance to environmental stressors compared with native species. In recent decades, the introduction of contaminants into the environment has increased as a result of industrialization. The objective of this study was to verify the resistance of bivalve mollusks from freshwater native (Anodontites trapesialis) and exotic (Limnoperna fortunei) species to chemical contamination using an ex vivo/in vitro approach. Gill and muscle tissues were exposed to two different types of environmental stressors, copper (metal), and Roundup Transorb® (herbicide). The tissues were submitted to a cytotoxicity test in which the lysosomal integrity was assessed, from the adaptation of a method to isolated cells, and multixenobiotic resistance (MXR) test which evaluated cellular defense. In the exotic species, only copper at 9000 µg/L and Roundup Transorb® at 5000 µg/L were cytotoxic. In the native species, copper cytotoxicity at 900 and 9000 µg/L and Roundup Transorb® at 50 and 5000 µg/L were observed. Results were the same in both tissues. The MXR, responsible for the extrusion of contaminants (cell defense), was inhibited in both species when exposed to the contaminants, this cell defense system seems to be more inhibited in the native species, when exposed to both pollutants, indicating greater sensitivity. Therefore, cytotoxicity may be related to the lack of capacity of cellular defense. In relation to lysosomal integrity, the native species was more sensitive to cytotoxic pollutants, where a greater number of experimental conditions of metals and herbicide showed cytotoxicity, as well as more experimental situations inhibited its ability to defend itself.


Assuntos
Bivalves/efeitos dos fármacos , Cobre/toxicidade , Herbicidas/toxicidade , Espécies Introduzidas , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/fisiologia , Brasil , Ecotoxicologia , Água Doce , Brânquias/química , Brânquias/efeitos dos fármacos , Glicina/análogos & derivados , Glicina/toxicidade , Lisossomos/efeitos dos fármacos , Músculos/efeitos dos fármacos , Mytilidae/efeitos dos fármacos , Mytilidae/fisiologia
16.
Aquat Toxicol ; 214: 105241, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301543

RESUMO

The purpose of this study was to investigate the bioaccumulation and biochemical responses exposed to one of the main organic ultraviolet (UV) pollutants in the environment, ethylhexyl methoxy cinnamate (EHMC), and its main transformation product, either alone or in combination in zebrafish (Danio rerio). Four-month-old zebrafish were exposed to EHMC (34.4, 344 nmol/L) solution for 14 days, the species and contents of EHMC transformation products in zebrafish were determined and 3,5-dichloro-2-hydroxyacetophenone (3,5DCl2HAcP) was the one with the highest concentration in transformation products. Then, zebrafish were exposed to EHMC, 3,5DCl2HAcP alone and mixed solution for 21 days. At 7, 14 and 21 d, the related indexes of antioxidant defense system were determined. Results showed that both EHMC and 3,5DCl2HAcP can lead to the increase of malondialdehyde (MDA) and glutathione (GSH) contents, superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) activities in visceral mass compared with the corresponding control group, thus produced oxidative stress effect in organism and 3,5DCl2HAcP even showed stronger oxidative stress than EHMC. The effects of the two lower concentration co-exposure groups were similar and more significant to that of single exposure groups, while excessive oxidative stress occurred at the highest co-exposure group indicated by the decrease of GSH content, SOD, CAT, GR activities and the continued increase of MDA content. At 21 d, estradiol (E2), vitellogenin (Vtg) and testosterone (T) contents, estrogen receptor (Esr), progesterone receptor (Pgr), androgen receptor (Ar), Vtg1, P450 aromatase (Cyp19a1) and 17ß-hydroxysteroid dehydrogenase (Hsd17b3) expression were all significantly increased when exposed to 3,5DCl2HAcP alone, showing complex estrogen and androgen effects. When exposed to EHMC alone, E2 and Vtg contents, Esr, Pgr, Vtg1, Cyp19a1 and Hsd17b1 gene expression levels decreased significantly, and T content and Ar and Hsd17b3 expression increased significantly, indicated that EHMC can produce anti-estrogen and androgen effect. Last, the decrease of estrogen effect and increase of androgen effect in co-exposure group suggested that 3,5DCl2HAcP might weaken the estrogen effect and promote the androgen effect of EHMC.


Assuntos
Cinamatos/metabolismo , Peixe-Zebra/metabolismo , Acetofenonas/metabolismo , Animais , Antioxidantes/metabolismo , Biotransformação/efeitos dos fármacos , Catalase/metabolismo , Cinamatos/toxicidade , Estradiol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Malondialdeído/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testosterona/metabolismo , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade
17.
EBioMedicine ; 46: 411-422, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31358477

RESUMO

BACKGROUND: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. METHODS: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. FINDINGS: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers. INTERPRETATION: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline. FUNDING: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.


Assuntos
Composição Corporal/efeitos dos fármacos , Dieta , Suplementos Nutricionais , Exercício , Músculos/efeitos dos fármacos , Músculos/metabolismo , Testosterona/administração & dosagem , Adolescente , Adulto , Biomarcadores , Peso Corporal/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Estudo de Prova de Conceito , Adulto Jovem
18.
Biomed Pharmacother ; 117: 108989, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228801

RESUMO

Korean pine nut protein (PNP) has a variety of biological activities, which are good for human health, but its ability to preventing diabetes has not been reported. This study evaluated the effects of water-soluble proteins of Korean pine nut obtained from a dilute alkali extract on carbohydrate metabolism of type 2 diabetic mice on a model of diabetes induced using a high fat diet combined with streptozotocin. The results showed that the hypoglycemic effect of PNP at a middle dose was the most significant, which was 38.7% lower than that of control. The extract significantly improved the oral glucose tolerance and liver indexes, increased the activity of the carbohydrate metabolism enzymes, and regulated the expression of the function of key genes for carbohydrate metabolism. It had a positive effect on both insulin resistance and glycolytic/gluconeogenesis signaling. In conclusion, PNP can regulate fasting blood glucose, improve insulin resistance, correct the glucose metabolism disorder in diabetic mice, and have a positive regulatory role. As the functional food, it has the potential to be beneficial in the treatment of type 2 diabetes mellitus as a new hypoglycemic functional food.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Proteínas de Nozes/uso terapêutico , Pinus/química , Água/química , Administração Oral , Aminoácidos/análise , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo dos Carboidratos/genética , Diabetes Mellitus Tipo 2/sangue , Dieta , Comportamento de Ingestão de Líquido , Jejum/sangue , Comportamento Alimentar , Regulação da Expressão Gênica/efeitos dos fármacos , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Proteínas de Nozes/administração & dosagem , Proteínas de Nozes/farmacologia , Solubilidade
19.
Environ Sci Pollut Res Int ; 26(23): 23242-23256, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190300

RESUMO

The aim of this study was to verify the effects of the isolated forms of Boral® SC 500, Glifosato® Biocarb herbicides, and a blend of both herbicides on metabolism and oxidative balance markers of Rana catesbeiana tadpoles and on their nutritional condition. Groups of tadpoles were divided into different treatments: control (no herbicides), Boral® 500 SC (sulfentrazone: 130 µg/L), Glifosato® Biocarb (glyphosate: 234 µg/L), and a blend of both herbicides. After 7 days, the liver, caudal muscle, and blood samples were taken to subsequently perform the biomarkers determination by spectrophotometry. The intestinal condition factor increased in animals exposed to glyphosate and herbicide blends, suggesting a hyperphagic effect. This hypothesis was confirmed by the rise of triglycerides and circulating very low-density lipoprotein (VLDL). There was a significant increase in the levels of uric acid in tadpoles exposed to the herbicide blend. Corticosterone levels reduced significantly in animals exposed to glyphosate and the herbicide blend. Oxidative stress markers had a tissue-dependent response. In the liver, glutathione S-transferase increased, and superoxide dismutase and catalase decreased in animals exposed to sulfentrazone and glyphosate. Lipoperoxidation was reduced in the glyphosate treatment. In the caudal muscle, superoxide dismutase and catalase activities were maintained, and there was a decline in the levels of glutathione S-transferase and TBARS only in the blend group.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Larva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sulfonamidas/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Glicina/metabolismo , Glicina/toxicidade , Herbicidas/metabolismo , Larva/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Rana catesbeiana , Sulfonamidas/metabolismo , Triazóis/metabolismo , Poluentes Químicos da Água/metabolismo
20.
PLoS One ; 14(6): e0217573, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170198

RESUMO

Pharmacological efficacy is based on the drug concentration in target tissues, which usually cannot be represented by the plasma concentration. The purpose of this study was to compare the pharmacokinetic characteristics of gemifloxacin in plasma and skeletal muscle and evaluate its tissue penetration in both healthy and MRSA (methicillin-resistant Staphylococcus aureus)-infected rats. A microdialysis (MD) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine free gemifloxacin concentrations in rat plasma and skeletal muscle simultaneously. The in vivo recoveries of MD were 23.21% ± 3.42% for skeletal muscle and 20.62% ± 3.19% for plasma, and were concentration independent. We provided evidence that the method developed here meets FDA requirements. Additionally, this method was successfully applied to the determination of free gemifloxacin in rats. Muscle and blood dialysates were collected after an 18 mg/kg intravenous bolus dose. The mean areas under the concentration-time curves (AUCs) from 0 to 9 h for skeletal muscle and plasma were 3641.50 ± 915.65 h*ng/mL and 7068.32 ± 1964.19 h*ng/mL in MRSA-infected rats and 3774.72 ± 700.36 h*ng/mL and 6927.49 ± 1714.86 h*ng/mL in healthy rats, respectively. There was no significant difference (P>0.05) in gemifloxacin exposure between healthy rats and MRSA-infected rats for plasma or muscle. The low ratio of AUC0-9 muscle to AUC0-9 plasma suggested lower drug exposure in skeletal muscle than in plasma for both healthy and MRSA-infected rats. Our study suggested that the administration of gemifloxacin according to drug levels in plasma to treat local infection is unreasonable and might result in an inadequate dose regimen.


Assuntos
Gemifloxacina/análise , Gemifloxacina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Microdiálise , Músculos/efeitos dos fármacos , Músculos/microbiologia , Espectrometria de Massas em Tandem , Animais , Proteínas Sanguíneas/metabolismo , Cromatografia Líquida , Ciprofloxacino/química , Ciprofloxacino/farmacologia , Modelos Animais de Doenças , Gemifloxacina/química , Gemifloxacina/farmacocinética , Masculino , Ligação Proteica , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Coxa da Perna/microbiologia , Distribuição Tecidual
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