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AIMS: Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice. METHODS AND RESULTS: Kefir consumption pre infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response. CONCLUSIONS: The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.
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Ticks have saliva rich in immunoregulatory molecules that interfere with the host's physiology in order to feed. This study aimed to evaluate the concentration of acute phase proteins and circulating oxidative stress in response to infestation by Amblyomma sculptum and Dermacentor nitens in two breed horses, Mangalarga Marchador and Breton Postier, to define resistance or susceptibility to ticks. Among the oxidative stress markers, we observed lower malondialdehyde and nitric oxide in horses with tick infestation, consequently not altering the antioxidant enzymes. Breton Postier with tick infestation showed a reduction in the ferric reducing ability of plasma (FRAP), which may be due to lower feeding of the host due to the stress caused by the infestation or even to sequestration of components induced by the tick during blood feeding. The alpha-1-antitrypsin, an acute phase protein, showed an increase in Mangalarga Marchador with tick infestation; curiously it is related to a protective action against tissue damage, pathogens and parasites. We could assume that Mangalarga Marchador showed a better response to ticks when compared to Breton Postier. However, it is still early to define the resistance or susceptibility to ticks, as we did not observe significant changes in most of the analyzed variables. Further studies are needed to understand the compounds and mechanisms of action of the tick saliva in the acute phase proteins and the possible relationships of oxidative stress in the host and the tick during blood feeding.
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Doenças dos Cavalos , Infestações por Carrapato , Carrapatos , Animais , Cavalos , Infestações por Carrapato/veterinária , Proteínas de Fase Aguda/metabolismo , Saliva , Estresse OxidativoRESUMO
Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore the objective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02 and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats.
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Quirópteros , Piretrinas , Animais , Quirópteros/fisiologia , Glicogênio , Mucinas , Necrose/induzido quimicamente , Óxido Nítrico , Nitrilas , Piretrinas/toxicidade , ÁguaRESUMO
Obesity is currently considered a public health problem with pandemic proportions and is associated with chronic low-grade inflammation, which can predispose to the development of several chronic diseases and metabolic complications. This cross-sectional population-based study, conducted with 743 Brazilian adults, aimed to evaluate the association between inflammatory cytokines with anthropometric measurements. Socio-demographic, anthropometric, behavioural and biochemical variables were collected. Multiple linear regression stratified by sex and adjusted for confounding factors was performed. In men, waist circumference (WC) was associated with IL-1ß (3·52 pg/ml; 95 % CI 0·60, 6·45), IL-6 (6·35 pg/ml; 95 % CI 0·35, 12·34), IL-8 (8·77 pg/ml; 95 % CI 2·37, 15·17), IL-10 (3·09 pg/ml; 95 % CI 0·56, 5·61), IL12p70 (8·31 pg/ml; 95 % CI 3·11, 13·52) and TNF-α (4·22 pg/ml; 95 % CI 0·20, 10·48). Waist:height ratio was associated with IL-6 (3·21 pg/ml; 95 % CI 0·02, 6·39). BMI was associated with IL-1ß (1·50 pg/ml; 95 % CI 0·46, 2·34), IL-6 (2·97 pg/ml; 95 % CI 0·78, 5·16), IL-8 (4·48 pg/ml; 95 % CI 2·21, 6·75), IL-10 (1·31 pg/ml; 95 % CI 0·30, 2·31), IL-12p70 (3·59 pg/ml; 95 % CI 1·24, 5·95) and TNF-α (2·00 pg/ml; 95 % CI 0·81, 3·19). In women, WC was associated with IL-6 (5·10 pg/ml; 95 % CI 0·68, 9·51) and IL-10 (4·16 pg/ml; 95 % CI 1·26, 7·06). BMI was associated with IL-6 (2·67 pg/ml; 95 % CI 0·34, 4·99), and WHR was associated with TNF-α (2·84 pg/ml; 95 % IC 0·86-6·54). The results highlight the importance of anthropometric assessment in clinical practice and the need to develop public policies and interventions to reduce the prevalence of obesity and, consequently, of inflammation and possible metabolic complications.
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The development of colorectal cancer involves some morphological changes, and in the initial stage, pre-neoplastic lesions called aberrant crypt foci (ACF) appear. Thus, an intervention with sources of bioactive compounds such as Hibiscus sabdariffa L., rich in phenolic compounds and anthocyanins, could attenuate the risk of developing these lesions due to its antioxidant, anti-inflammatory and anti-proliferative properties. Therefore, the aim of this study was to evaluate the effects of 5% and 10% supplementation of dehydrated H. sabdariffa calyces (DHSC) during the development of 1,2-dimethylhydrazine-induced preneoplastic lesions in male BALB/c mice. The characterization of DHSC was carried out. The in vivo experiment lasted 12 weeks, and the animals were randomly divided into 3 experimental groups: the control group (CON) and the supplemented groups with 5% DHSC and 10% DHSC. The activities of liver enzymes catalase and superoxide dismutase were determined. In addition, ACF, short chain fatty acids (SCFA), presence of inflammatory infiltrates, goblet cells and leukocytes in the colonic mucosa were quantified. There was a significant reduction in ACF and the presence of inflammatory infiltrates in the colon of animals in groups 5DHSC and 10DHSC. In addition, the 10DHSC group showed an increase in the activity of the catalse enzyme, in the production of butyrate and in the presence of NK cells in the colon, in addition to more hypertrophied goblet cells. Based on these findings, it is suggested that DHSC supplementation may be recommended to attenuate cellular responses in the early stage of preneoplastic lesions.
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2-phenylethanol (2-PE) is a higher aromatic alcohol with a rose-like aroma used in the cosmetic and food industries as a flavoring and displays potential for application as an antifungal. Biotechnological production of 2-PE from yeast is an interesting alternative due to the non-use of toxic compounds and the generation of few by-products. Kluyveromyces marxianus CCT 7735 is a thermotolerant strain capable of producing high 2-PE titers from L-Phenylalanine; however, like other yeast species, its growth has been strongly inhibited by this alcohol. Herein, we aimed to evaluate the effect of 2-PE on cell growth, cell viability, membrane permeability, glucose uptake, metabolism, and morphology in K. marxianus CCT 7735, as well as its adaptive responses. The stress condition was imposed after 4 h of cultivation by adding 3.0 g.L-1 of 2-PE in exponential growing cells. 2-PE stress impaired yeast growth, glucose uptake, fermentative metabolism, membrane permeability, and cell viability. Moreover, the stress condition provoked changes in both morphology and surface roughness. The reactive oxygen species (ROS) increased immediately on exposure to 2-PE. Changes in membrane fatty-acid composition, ergosterol content, exopolysaccharides production, and reduction of the ROS levels appear to be the result of adaptive responses in K. marxianus. Our results provided insights into a better understanding of the effects of 2-PE on K. marxianus and its adaptive responses.
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Adaptação Fisiológica , Polissacarídeos Fúngicos/metabolismo , Kluyveromyces/efeitos dos fármacos , Kluyveromyces/metabolismo , Álcool Feniletílico/farmacologia , Permeabilidade da Membrana Celular , Ergosterol/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Lipídeos de Membrana/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse FisiológicoRESUMO
PURPOSE: Evidence from epidemiological and clinical studies suggests that nut consumption provides satiety and may contribute to the management of obesity. However, the effect of acute intake of nuts on appetite responses remains unclear. The objective of this study was to evaluate the acute effect of a shake containing 30 g of cashew nuts (Anacardium occidentale L.) and 15 g of Brazil nuts (Bertholletia excelsa H.B.K) on appetite responses in overweight subjects. METHODS: This was a clinical, randomized, controlled, single-blind, cross-over, pilot study. On two non-consecutive test days, 15 subjects received a shake containing nuts, and a shake absent of nuts matched for energy and macronutrient content. Subjective appetite sensation was evaluated by visual analogue scales (VAS). Food intake was measured by weighing the lunch served at the end of each morning-test, which subjects ate ad libitum. Total energy intake was estimated by food records. This study is registered on the Brazilian Registers of Clinical Trials-ReBEC (protocol: U1111-1203-9891). RESULTS: We observed no significant difference in subjective appetite sensations between the groups. Food intake at lunch, as well as energy intake throughout the day also did not differ between the treatments. CONCLUSION: Our results suggest that the acute intake of a shake containing nuts was not able to enhance satiety, compared to a shake matched for energy and macronutrient content. Further studies are warranted to elucidate the satiety mechanisms of nuts intake.
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Anacardium , Bertholletia , Apetite , Estudos Cross-Over , Ingestão de Energia , Humanos , Nozes , Sobrepeso , Projetos Piloto , Saciação , Método Simples-CegoRESUMO
Green tea is a popular drink used for therapeutic purposes to mitigate the consequences of diabetes. In this study, we aimed at evaluating the potential of green tea infusion to ameliorate structural and enzymatic damages caused by hyperglycemia in the testis and epididymis of Wistar rats. For that, nondiabetic and streptozotocin-induced diabetic rats (negative control and diabetes control, respectively) received 0.6 mL of water by gavage. Another set of diabetic animals received 100 mg/kg of green tea infusion diluted in 0.6 mL of water/gavage (diabetes + green tea) daily. After 42 days of treatment, the testes and epididymides were removed and processed for histopathological analysis, micromineral determination, and enzymatic assays. The results showed that treatment with green tea infusion preserved the testicular and epididymal histoarchitecture, improving the seminiferous epithelium and the sperm production previously affected by diabetes. Treatment with green tea reduced tissue damages caused by this metabolic condition. Given the severity of hyperglycemia, there was no efficacy of the green tea infusion in maintaining the testosterone levels, antioxidant enzyme activity, and microminerals content. Thus, our findings indicate a protective effect of this infusion on histological parameters, with possible use as a complementary therapy for diabetes.
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The consumption of food with MUFA has been associated with improvement of inflammation and oxidative stress in overweight individuals. In the present study, we evaluate the effect of high-oleic peanut intake within a hypoenergetic diet on inflammatory and oxidative status markers in overweight men. Sixty-four overweight men (BMI 26-35 kg/m2, 18-50 years old) participated in this randomised controlled study for 4 weeks, allocated into three groups: control (CT, n 22), conventional peanut (CVP, n 21) and high-oleic peanut (HOP, n 21). They followed a hypoenergetic diet (-250 kcal/d; -1045 kJ/d) with or without 56 g of high-oleic or conventional peanuts. After the intervention, the inflammatory markers did not show significant changes in fasting concentrations or postprandial response among the experimental groups (P > 0·05). The activity of oxidative status markers remained unchanged after the intervention. However, in the CT, malondialdehyde showed lower concentration in comparison with the baseline (P = 0·020) and among the groups (P = 0·002). In the present study, the daily intake of high-oleic peanuts within a hypoenergetic diet did not modify the inflammatory markers and oxidative status in overweight men. More studies are needed to better understand the effect of high-oleic peanut intake on health outcomes.
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Arachis/química , Restrição Calórica , Ingestão de Energia , Inflamação/prevenção & controle , Ácido Oleico/química , Estresse Oxidativo , Adulto , Humanos , Masculino , SobrepesoRESUMO
Deltamethrin (DTM) is a synthetic pyrethroid insecticide highly used by farmers and home users. This pesticide has lipophilic properties that facilitate a high absorption and can cause toxicity in non-target organisms. During foraging, the fruit-eating bats Artibeus lituratus are exposed to pesticides. However, the knowledge of the toxicity of pesticides on the physiology of bats is relatively scarce. This study aimed to check the toxicity of short-term exposure to low concentration of DTM on fruit-eating bat A. lituratus. After seven days of exposure to two doses of DTM (0.02 and 0.04mg/kg of papaya), the fruit bats showed an increase in the enzyme aspartate aminotransferase, alanine aminotransferase, and hyperglycemia. The liver and pectoral muscle presented oxidative stress. In the liver, the hydrogen peroxide (H2O2) and nitric oxide (NO) were increased as well as the antioxidant glutathione (GSH), the activity of glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) but in a lesser extent. Yet, total lipids were increased while hepatic glycogen content is reduced. The pectoral muscle showed NO, SOD, CAT, malondialdehyde (MDA), and carbonyl increased protein levels in both concentrations of DTM. All these results show that low doses of DTM can cause hepatic and muscular toxicity and induce changes in carbohydrate metabolism. Physiological changes caused by exposure to DTM in bats may have direct consequences in flight capacity, reproduction, and metabolism of these animals.
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Quirópteros/metabolismo , Metabolismo Energético/efeitos dos fármacos , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Nitrilas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Piretrinas/toxicidade , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Catalase/metabolismo , Ingestão de Alimentos , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Peróxido de Hidrogênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Músculo Esquelético/metabolismo , Superóxido Dismutase/metabolismoRESUMO
In the present work, we have investigate the cellular immune response of Galleria mellonella larvae against three strains of the gram-negative bacterium Actinobacillus pleuropneumoniae: low-virulence (780), high-virulence (1022) and the serotype 8 reference strain (R8). Prohemocytes, plasmatocytes, granulocytes, oenocytoids and spherulocytes were distinguished according to their size and morphology, their molecular markers and dye-staining properties and their role in the immune response. Total hemocyte count, differential hemocyte count, lysosome activity, autophagic response, cell viability and caspase-3 activation were determined in circulating hemocytes of naive and infected larvae. The presence of the autophagosome protein LC3 A/B within the circulating hemocytes of G. mellonella was dependent on and related to the infecting A. pleuropneumoniae strain and duration of infection. Hemocytes treated with the high-virulence strain expressed higher levels of LC3 A/B, whereas treatment with the low-virulence strain induced lower expression levels of this protein in the cells. Moreover, our results showed that apoptosis in circulating hemocytes of G. mellonella larvae after exposure to virulent bacterial strains occurred simultaneously with excessive cell death response induced by stress and subsequent caspase-3 activation.
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Actinobacillus pleuropneumoniae/imunologia , Hemócitos/imunologia , Hemócitos/microbiologia , Mariposas/imunologia , Mariposas/microbiologia , Infecções por Actinobacillus/imunologia , Infecções por Actinobacillus/veterinária , Animais , Autofagia , Contagem de Células , Hemócitos/citologia , Imunidade Celular , Larva/citologia , Larva/imunologia , Larva/microbiologia , Mariposas/citologia , Mariposas/crescimento & desenvolvimentoRESUMO
Quorum sensing (QS) is cell-cell communication mechanism mediated by signaling molecules known as autoinducers (AIs) that lead to differential gene expression. Salmonella is unable to synthesize the AI-1 acyl homoserine lactone (AHL), but is able to recognize AHLs produced by other microorganisms through SdiA protein. Our study aimed to evaluate the influence of AI-1 on the abundance of proteins and the levels of organic acids of Salmonella Enteritidis. The presence of N-dodecyl-homoserine lactone (C12-HSL) did not interfere on the growth or the total amount of extracted proteins of Salmonella. However, the abundance of the proteins PheT, HtpG, PtsI, Adi, TalB, PmgI (or GpmI), Eno, and PykF enhanced while the abundance of the proteins RplB, RplE, RpsB, Tsf, OmpA, OmpC, OmpD, and GapA decreased when Salmonella Enteritidis was anaerobically cultivated in the presence of C12-HSL. Additionally, the bacterium produced less succinic, lactic, and acetic acids in the presence of C12-HSL. However, the concentration of extracellular formic acid reached 20.46 mM after 24 h and was not detected when the growth was in the absence of AI-1. Considering the cultivation period for protein extraction, their abundance, process and function, as well as the levels of organic acids, we observed in cells cultivated in presence of C12-HSL a correlation with what is described in the literature as entry into the stationary phase of growth, mainly related to nitrogen and amino acid starvation and acid stress. Further studies are needed in order to determine the specific role of the differentially abundant proteins and extracellular organic acids secreted by Salmonella in the presence of quorum sensing signaling molecules.
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4-Butirolactona/análogos & derivados , Ácidos/metabolismo , Proteínas de Bactérias/metabolismo , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/fisiologia , 4-Butirolactona/farmacologia , Etanol/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica/métodos , Percepção de Quorum , Salmonella enteritidis/crescimento & desenvolvimentoRESUMO
The characterization of gut microbiota has become an important area of research in several clinical conditions, including type 2 diabetes (T2DM). Changes in the composition and/or metabolic activity of the gut microbiota can contribute to human health. Thus, this review discusses the effects of probiotics and gut microbiota on metabolic control in these individuals. Relevant studies were obtained from electronic databases such as PubMed/Medline and ISI Web of Science. The main probiotics used in these studies belonged to the genera Lactobacillus and Bifidobacterium. The authors found seven randomized placebo-controlled clinical trials and 13 experimental studies directly related to the effect of probiotics on metabolic control in the context of T2DM. The hypothesis that gut microbiota plays a role in the development of diabetes indicates an important beginning, and the potential of probiotics to prevent and reduce the severity of T2DM is better observed in animal studies. In clinical trials, the use of probiotics in glycemic control presented conflicting results, and only few studies have attempted to evaluate factors that justify metabolic changes, such as markers of oxidative stress, inflammation, and incretins. Thus, further research is needed to assess the effects of probiotics in the metabolism of diabetic individuals, as well as the main mechanisms involved in this complex relationship.
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Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Animais , Bifidobacterium , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , LactobacillusRESUMO
The ants use their venom for predation, defense, and communication. The venom of these insects is rich in peptides and proteins, and compared with other animal venoms, ant venoms remain poorly explored. The objective of this study was to evaluate the protein content of the venom in the Ponerinae ant Pachycondyla striata. Venom samples were collected by manual gland reservoir dissection, and samples were submitted to two-dimensional gel electrophoresis and separation by ion-exchange and reverse-phase high-performance liquid chromatography followed by mass spectrometry using tanden matrix-assisted laser desorption/ionization with time-of-flight (MALDI-TOF/TOF) mass spectrometry and electrospray ionization-quadrupole with time-of-flight (ESI-Q/TOF) mass spectrometry for obtaining amino acid sequence. Spectra obtained were searched against the NCBInr and SwissProt database. Additional analysis was performed using PEAKS Studio 7.0 (Sequencing de novo). The venom of P. striata has a complex mixture of proteins from which 43 were identified. Within the identified proteins are classical venom proteins (phospholipase A, hyaluronidase, and aminopeptidase N), allergenic proteins (different venom allergens), and bioactive peptides (U10-ctenitoxin Pn1a). Venom allergens are among the most expressed proteins, suggesting that P. striata venom has high allergenic potential. This study discusses the possible functions of the proteins identified in the venom of P. striata.
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Venenos de Formiga/química , Formigas/fisiologia , Proteínas de Insetos/química , Proteômica , AnimaisRESUMO
Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis fruit, its complex with copper against Streptococcus spp. isolated from bovine mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC-T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with optical activity. Its vibrational spectrum in the infrared region showed absorption bands in the high-frequency region, as well as bands that can be attributed to the unconjugated and conjugated stretching of the free ligand. The complex was anhydrous. One of the tested bacterial strains was not sensitive to the compounds, while the other three had MIC values of 7.8 µg mL-1 and minimum bactericidal concentration (MBC) values between 15.6 and 31.3 µg mL-1. These two compounds are bacteriostatic, did not cause damage to the cell wall and, at sub-inhibitory concentrations, did not induce bacterial adhesion. The compounds were not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable antimicrobial properties and could potentially be used in bovine mastitis treatment.
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Antibacterianos/farmacologia , Benzofenonas/farmacologia , Benzoquinonas/farmacologia , Glândulas Mamárias Animais/citologia , Mastite Bovina/microbiologia , Streptococcus/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Aderência Bacteriana , Benzofenonas/química , Benzofenonas/toxicidade , Benzoquinonas/química , Benzoquinonas/toxicidade , Bovinos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/toxicidade , Cobre/química , Feminino , Glândulas Mamárias Animais/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus/isolamento & purificação , Streptococcus/fisiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Streptococcus agalactiae/fisiologiaRESUMO
In the present investigation, a collection of nineteen 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones was synthesized and screened for their cytotoxic activity against a panel of three leukemia cancer cell lines. The compounds were prepared via ZrOCl2·8H2O catalyzed condensation reactions between phthalaldehydic acid and different acetophenones. The reactions were carried out free of solvent and the isobenzofuran-1(3H)-ones were obtained in good yields (80-92%). The identities of the synthesized compounds were confirmed upon IR and NMR ((1)H and (13)C) spectroscopy as well as high resolution mass spectrometry analyses. Structures of compounds 1, 4 and 16 were also investigated by X-ray analysis. The synthesized compounds were submitted to in vitro bioassays against HL-60, K562 and NALM6 cancer cell lines using MTT cytotoxicity assay. After 48h of treatment, twelve derivatives were able to reduce cell viability and presented IC50 values equal to or below 20µmolL(-1) against at least one of the evaluated lineages. The most active compound corresponded to 3-(3-methylphenyl-2-oxoethyl)isobenzofuran-1(3H)-one (18) (IC50 values obtained for HL-60, K562 and NALM6 were, respectively, 13.5µmolL(-1), 8.83µmolL(-1), and 5.24µmolL(-1)). In addition, compound 18 was capable of triggering apoptosis on NALM6 cells. All isobenzofuranones herein evaluated did not present cytotoxicity on peripheral blood mononuclear cells (PBMC), suggesting selective cytotoxic effect on leukemic cells. A computational study allowed prediction of pharmacokinetics and drug-likeness properties of the synthesized compounds. DFT calculations were performed to obtain the energy values of HOMO, LUMO, and dipole moments of isobenzofuranones.
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Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzofuranos/síntese química , Benzofuranos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Teoria Quântica , Relação Estrutura-AtividadeRESUMO
PURPOSE: Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria might be an inflammation trigger in adipose tissue. It has recently been proposed that there is a link between adipose tissue distribution and blood LPS. However, the number of studies on this topic is scarce, and further investigation in humans is required. In this study, we explored the association between plasma LPS concentrations and body fat distribution, as well as the biochemical parameters that may indicate the presence of metabolic disorders. METHODS: Sixty-seven young adult men with body mass index of 26-35 kg/m(2) were evaluated. Anthropometry, body composition and body fat distribution, blood pressure, energy expenditure, physical activity level, dietary intake, and biochemical parameters were assessed. RESULTS: Men with median plasma LPS ≥ 0.9 EU/mL presented higher sagittal abdominal diameter, trunk fat percentage, and android fat percentage, and mass, insulin and alanine aminotransferase concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell dysfunction (HOMA-B) than those with lower plasma LPS. LPS correlated positively with the trunk fat percentage, and android fat percentage, and mass, insulin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations, as well as HOMA-IR and HOMA-B. CONCLUSION: Our results suggest that a higher plasma LPS concentration is associated with a less favorable phenotype as characterized by higher central adiposity, higher values of HOMA-IR, and beta cell function impairment in overweight/obese men.
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Lipopolissacarídeos/sangue , Obesidade/sangue , Sobrepeso/sangue , Tecido Adiposo/metabolismo , Adolescente , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Pressão Sanguínea , Composição Corporal , Distribuição da Gordura Corporal , Índice de Massa Corporal , Estudos Transversais , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Metabolismo Energético , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Atividade Motora , Fenótipo , Adulto JovemRESUMO
The bacterium Mycoplasma hyopneumoniae (Mhp) causes a chronic infectious respiratory disease in pigs, leading to important economic losses. This study aimed to compare the immune response of the local Piau breed and a commercial line to Mhp vaccination. For this, two phases were carried out. In the first, gene expression of toll-like receptors (TLR2, TLR4, TLR6, and TLR10) and cytokines (IL2, IL6, IL8, IL10, IL12, IL13, TNFα, and TGFß) was assessed in porcine blood mononuclear cells (PBMC) from the two genetic groups before and after vaccination. In the second experiment, nitric oxide production, specific antibodies, and gene expression of toll-like receptors and cytokines were evaluated in bronchoalveolar lavage fluid (BALF) cells of vaccinated and unvaccinated pigs. After vaccination against Mhp, TLR2, TLR4, TLR6, TLR10, IL6, TNFα, and TGFß expression levels were elevated in PBMC from commercial animals, and TLR6, TLR10, and TGFß expression levels were elevated in PBMC from the Piau group. Vaccination also increased the production of Mhp-specific IgG antibodies in BALF cells in the Piau breed. Comparison of the two genetic groups revealed differences in TNFα and IL10 expression in BALF cells. These results show that Piau pigs have different immune responses to vaccination compared with commercial animals. It is worth noting that these genetic differences between both genetic groups may be related to phenotypic differences in Mhp resistance or susceptibility.
RESUMO
This study evaluated the effect of prepubertal arsenic exposure in the liver and kidney of pubescent rats and their reversibility 30 days after arsenic withdrawal. Male pups of Wistar rats (21 days old) were divided into two groups (n = 20/group): control animals received filtered water, and exposed rats received 10 mg L-1 arsenic from postnatal day (PND) 21 to PND 51. The liver and kidney of 52 days old rats (n = 10/group) were examined to investigate the effects of arsenic on micromineral content, antioxidant enzyme activity, histology, and biochemistry parameters. The other animals were kept alive under free arsenic conditions until 82 days old and further analyzed by the same parameters. Our results revealed that 52-day-old rats increased arsenic content in their liver and arsenic and manganese in their kidney. In those animals, glycogen and zinc content and catalase activity were reduced in the liver, and the selenium content decreased in the kidney. Thirty days later, arsenic reduced the manganese and iron content and SOD and CAT activity in the liver of 82-day-old rats previously exposed to arsenic, while glycogen and selenium content decreased in their kidney. In contrast, PND 82 rats exhibited higher retention of copper in the liver, an increase in iron and copper content, and CAT and GST activity in the kidney. Significant histological alterations of liver and kidney tissues were not observed in rats of both ages. We conclude that arsenic-induced toxicity could alter differently the oxidative status and balance of trace elements in pubertal and adult rats, demonstrating that the metalloid can cause effects in adulthood.
Assuntos
Arsênio , Selênio , Ratos , Masculino , Animais , Arsênio/metabolismo , Cobre/farmacologia , Ratos Wistar , Selênio/farmacologia , Selênio/metabolismo , Manganês/farmacologia , Catalase/metabolismo , Antioxidantes/metabolismo , Fígado/metabolismo , Rim/metabolismo , Ferro/metabolismo , Estresse Oxidativo , Glicogênio/metabolismoRESUMO
Mastitis, an inflammation of the mammary gland affecting milk production and quality in dairy herds, is often associated with Staphylococcus spp. in goats. Neutrophils are crucial in combating infections by migrating into milk and deploying various defense strategies, including the release of neutrophil extracellular traps (NETs) composed of DNA, histones, and bactericidal proteins. This study investigated whether NETs are released by goat neutrophils stimulated in vitro by Staphylococcus aureus and Staphylococcus warneri, two common pathogens of goat mastitis. PMNs were isolated from blood from healthy adult goats. We evaluated goat NET formation by stimulating cells with: phorbol 12-myristate 13-acetate (PMA) as a positive control, cytochalasin for inhibition of actin polymerization, S. aureus, and S. warneri. NET formation was observed in response to chemical stimulation and bacterial presence, effectively trapping pathogens. Variations in NET formation between S. aureus and S. warneri suggest pathogen-specific responses. These findings suggest that the formation of NETs may be an important complementary mechanism in the defense against mastitis in goats. In conclusion, this study unveils a novel defense mechanism in goats, indicating the role of NETs against S. aureus and S. warneri in mastitis.