RESUMO
Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.
Assuntos
Anestésicos Locais , Benzocaína , Portadores de Fármacos , Lipídeos , Benzocaína/administração & dosagem , Benzocaína/química , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Anestésicos Locais/farmacocinética , Anestésicos Locais/farmacologia , Portadores de Fármacos/química , Animais , Lipídeos/química , Camundongos , Nanoestruturas/química , Liberação Controlada de Fármacos , Masculino , Nanopartículas/químicaRESUMO
Although several testicular alterations promoted by coronavirus infection have been demonstrated, the extent, causes, and players of testicular pathogenesis are not totally understood. The present study aimed to investigate the short-term effects on male fertility of intranasally administered murine hepatitis virus strain 3 (MHV-3), a member of the genus Betacoronavirus, which causes a severe systemic acute infection. This mouse model might be used as a in vivo prototype for investigating the impact of betacoronavirus on the endocrine and exocrine testicular functions with the advantage to be performed in a biosafety level 2 condition. Herein, we performed virological, histopathological, and molecular studies regarding the testicular spermatogenesis and the spermatic quality analyses in an MHV-3-infected C57BL/6 mice. The main outcomes showed that MHV-3 infects mouse testis and induces a testicular inflammatory state, impairing the steroidogenic pathway. The infection led to several alterations in the testicular parenchyma, such as: seminiferous epithelium sloughing, retention of residual bodies, germ cell apoptosis, alterations in intercellular junction proteins, and worse spermatogenic parameters. Moreover, the levels of plasmatic testosterone as well as the quality of sperm production reduced. Therefore, the present data suggest that the viral/inflammatory impairment of the steroidogenic pathway and the consequent imbalance of androgen levels is critical in testicular pathology, disturbing the SC barrier function and the germ cell differentiation. Our study is important for comprehending the effects of beta coronavirus infections on testis function in order to develop treatments that could prevent virus-mediated male infertility.
Assuntos
Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina , Espermatogênese , Espermatozoides , Testículo , Animais , Masculino , Camundongos , Testículo/virologia , Testículo/patologia , Testículo/imunologia , Espermatozoides/virologia , Espermatozoides/imunologia , Espermatozoides/patologia , Modelos Animais de Doenças , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/imunologia , Infertilidade Masculina/virologia , Infertilidade Masculina/imunologia , Infertilidade Masculina/patologia , Infertilidade Masculina/etiologia , Testosterona/sangue , HumanosRESUMO
Allergic asthma is a chronic disease mainly characterised by eosinophil inflammation and airway remodelling. Many studies have shown that the gut microbiota of allergic individuals differs from that of non-allergic individuals. Although high levels of bifidobacteria have been associated with healthy persons, Bifidobacterium adolescentis ATCC 15703, a gut bacteria, has been associated with allergic individuals in some clinical studies. The relationship between B. adolescentis ATCC 15703 and asthma or allergies has not been well elucidated, and its effect may be dependent on the host's genetic profile or disease state. To elucidate this question, we evaluated the role of preventive B. adolescentis ATCC 15703 treatment on experimental allergic airway inflammation in two genetically different mouse strains, Balb/c and C57BL/6 (B6). Balb/c mice display a greater predisposition to develop allergic responses than B6 mice. Oral preventive treatment with B. adolescentis ATCC 15703 modulated experimental allergic airway inflammation, specifically in Balb/c mice, which showed decreased levels of eosinophils in the airway. B6 mice did not exhibit any significant alterations in eosinophils but showed an increased influx of total leukocytes and neutrophils into the airway. The mechanism underlying the beneficial effects of these bacteria in experimental allergic mice may involve products of bacteria metabolism, as dead bacteria did not mimic the ability of live B. adolescentis ATCC 15703 to attenuate the influx of eosinophils into the airway. To conclude, preventive oral B. adolescentis ATCC 15703 treatment can attenuate the major characteristic of allergic asthma, eosinophil airway influx, in Balb/c but not B6 mice. These results suggest that oral treatment with this specific live bacterial strain may have therapeutic potential for the treatment of allergic airway disease, although its effect is mouse-strain-dependent.
Assuntos
Asma/prevenção & controle , Bifidobacterium adolescentis/crescimento & desenvolvimento , Probióticos/administração & dosagem , Sistema Respiratório/patologia , Administração Oral , Animais , Modelos Animais de Doenças , Eosinófilos/imunologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Resultado do TratamentoRESUMO
Antioxidant compounds have the ability to scavenge the reactive oxygen species in an attempt to minimise damage in seeds during the germination. This study aimed to evaluate the physiological and metabolic process of two well-established antioxidant compounds: kojic acid and hydroxyphenyl ethanol (tyrosol), at increasing concentrations, on wheat seeds. The use of different concentrations of tyrosol or kojic acid not showed any interference on seed germination rate. However, we observed isolated effect of antioxidants and their concentrations to: germination speed index, shoot length and electrolyte leakage; and significant interaction between the factors to: seedling total length, seedling fresh matter and α-amylase activity. Our results suggest that the use of antioxidant molecules can be applied on seed treatments for protection against damage oxidative stress and improve seed metabolism.
Assuntos
Fungos/química , Germinação/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Pironas/farmacologia , Triticum/efeitos dos fármacos , Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Endófitos/química , Estresse Oxidativo , Álcool Feniletílico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Plântula/efeitos dos fármacos , Sementes/efeitos dos fármacosRESUMO
This study evaluates the trace metal composition and fractionation in sludge samples from anaerobic sewage treatment plants from six cities in Brazil. Ten metals were evaluated: Ni, Mn, Se, Co, Fe, Zn, K, Cu, Pb and Cr. Specific methanogenic activity of the sludge was also evaluated using acetic acid as the substrate. Among the essential trace metals for anaerobic digestion, Se, Zn, Ni and Fe were found at a high percentage in the organic matter/sulfide fraction in all sludge samples analyzed. These metals are less available for microorganisms than other metals, i.e., Co and K, which were present in significant amounts in the exchangeable and carbonate fractions. Cu is not typically reported as an essential metal but as a possible inhibitor. One of the samples showed a total Cu concentration close to the maximal amount allowed for reuse as fertilizer. Among the non-essential trace metals, Pb was present in all sludge samples at similar low concentrations and was primarily present in the residual fraction, demonstrating very low availability. Cr was found at low concentrations in all sludge samples, except for the sludge from STP5; interestingly, this sludge presented the lowest specific methanogenic activity, indicating possible Cr toxicity.
Assuntos
Metais Pesados/química , Esgotos/química , Brasil , Fracionamento QuímicoRESUMO
Ovarian hormone loss is associated with a shift in fat distribution to intra-abdomin al adipose tissue (intra-AAT) depots and with lipid metabolism disorders, which predisposes individuals to developing insulin resistance. Resistance training (RT) prevents increases in intra-AAT after ovarian hormone loss. However, the molecular mechanisms underlying these changes remain unclear. We investigated the effects of ovariectomy and RT on gene expression related to lipogenesis and fat oxidation in the intra-AAT of ovariectomized rats. Sprague-Dawley rats (n=6/group) were divided into the groups: sham-sedentary, ovariectomized-sedentary, sham-RT and ovariectomized-RT. RT groups performed a 10-week climbing program on a ladder with progressive overload. Intra-AAT was subjected to morphometric and mRNA analysis. Ovariectomized-sedentary group had larger adipocytes and higher expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), hormone-sensitive lipase (HSL) and lower expression of the oxidative carnitinepalmitoyltransferase-I (CPT-1). RT counteracted OVX-induced increases in PPAR-γ and SCD-1 and decreased SREBP-1c. ACC and HSL were downregulated in ovariectomized-RT compared with the ovariectomized-sedentary group. Ovariectomized-RT group had the highest CPT-1 gene expression. Adipocyte size decreased in ovariectomized-RT group. Results suggest that RT reduces intra-AAT adipocyte size in ovariectomized rats by suppressing intra-AAT fatty acid synthesis and enhancing fatty acid ß-oxidation.
Assuntos
Ácidos Graxos/biossíntese , Gordura Intra-Abdominal/metabolismo , Lipogênese , Menopausa/metabolismo , Treinamento Resistido , Adipócitos/citologia , Animais , Glicemia/metabolismo , Índice de Massa Corporal , Tamanho Celular , Ingestão de Alimentos , Feminino , Expressão Gênica , Lipogênese/genética , Modelos Animais , Ovariectomia , Oxirredução , Ratos Sprague-DawleyRESUMO
Asiaticoside is a triterpenoid present in Centella asiatica extract, responsible for the therapeutic activity of this plant in chronic liver disease. The hepatocyte is the cell responsible for the endocrine and exocrine functions of the liver, in addition to the conversion of harmful substances into non-toxic compounds that are excreted in the bile. That is why the liver is sensitive to the action of some drugs, such as paracetamol. Hence, paracetamol was used as an experimental model of liver damage, with the aim of assessing the effectiveness of asiaticoside, in a standard therapeutic dose, as a hepatoprotector in Wistar rats. In this experiment, 40 animals were used and divided into two groups: those treated with asiaticoside and the untreated control group. Animals from the first group were subjected to pretreatment with the active ingredient (1mg/kg/dia P.O.) for eight days and exposed to a toxic dose of paracetamol (3 g/kg P.O.) on the eighth day. After 24 h and 72 h, these rats were sacrificed for the collection of blood samples and liver fragments. To assess hepatoprotective activity, serum enzymes (AST, ALT and alkaline phosphatase) indicative of liver damage were measured and histological and morphological analyses of liver tissue were performed. The results obtained showed that asiaticoside exerted hepatoprotective action, since it promoted a reduction in histological lesions and a decrease in serum levels of AST and ALT. From these results, we conclude that asiaticoside, in the dose most commonly used in herbal medicine, protects the liver against acute hepatitis induced by paracetamol...
O asiaticosídeo é um triterpenóide presente no extrato da Centella asiatica, sendo responsável pela atividade terapêutica desta planta em doenças hepáticas crônicas. O hepatócito é a célula responsável pelas funções endócrinas e exócrinas do fígado, além de converter substâncias nocivas em materiais não tóxicos excretados pela bile. Por esse motivo, o fígado é sensível à ação de alguns fármacos, como, por exemplo, o paracetamol. Assim, utilizando o paracetamol como modelo experimental de lesão hepática, o objetivo deste estudo foi avaliar a ação hepatoprotetora do asiaticosídeo, na dose estabelecida como terapêutica, em ratos Wistar. Dois grupos compostos por vinte animais cada, tratados com asiaticosídeo (1mg/kg/dia v.o.) por oito dias e não tratados foram submetidos à intoxicação com elevada dose de paracetamol (3 g/kg v.o) no oitavo dia. Em seguida, os animais foram eutanasiados após 24 h ou 72 h para coleta de amostras de sangue e fragmentos de fígado. Para avaliação da atividade hepatoprotetora, foi realizada a dosagem sérica de enzimas indicativas de lesão hepática (AST, ALT e Fosfatase Alcalina) e a análise histológica e morfométrica do tecido hepático. Os resultados obtidos permitiram evidenciar que na dose utilizada, o asiaticosídeo apresenta atividade hepatoprotetora, uma vez que o grupo submetido ao tratamento prévio apresentou menos lesões histológicas e menores níveis séricos de AST e ALT quando comparado ao grupo controle. Estes resultados permitem concluir que o asiaticosídeo, na dose mais usualmente empregada na fitoterapia, apresentou atividade hepatoprotetora na hepatite aguda causada por elevada dose de paracetamol...
Assuntos
Animais , Masculino , Ratos , Acetaminofen/toxicidade , Extratos Vegetais/farmacologia , Ratos WistarRESUMO
The growth of maritime transport and oil exploitation activities may increase the risk of oil spills. Thus, plans and actions to prevent or mitigate impacts are needed to minimize the effects caused by oil. However, tools used worldwide to support contingency plans have not been integrated, thus leading to failure in establishing priority areas. This investigation aimed to develop indices of environmental vulnerability to oil (IEVO), by combining information about environmental sensibility to oil and results of numerical modeling of spilled oil. To achieve that, a case study concerning to oil spills scenarios in a subtropical coastal area was designed, and IEVOs were calculated and presented in maps, in order to make the information about the areas' vulnerability more easily visualized. For summer, the extension of coastline potentially affected by oil was approximately 150 km, and most of the coastline presented medium to high vulnerability. For winter, 230 km coastline would be affected, from which 75% were classified as medium to high vulnerability. Thus, IEVO maps allowed a rapid and clearer interpretation of the vulnerability of the mapped region, facilitating the planning process and the actions in response to an oil spill.