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1.
Plant Foods Hum Nutr ; 74(3): 316-321, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31119466

RESUMO

Inositol hexaphosphate (IP6), a food constituent with various health benefits, has been shown to suppress postprandial elevations of serum uric acid (SUA) levels in healthy adults by inhibiting purine nucleoside and base absorption. Here, we investigated the effect of repeated intake of IP6 on fasting SUA levels in hyperuricemic subjects. This randomized double-blind placebo-controlled crossover design study included 31 asymptomatic hyperuricemic subjects (fasting SUA level > 7.0 but <9.0 mg/dL). Subjects ingested placebo or IP6 drinks (600 mg twice daily) during two 2-week intervention periods with a 2-week washout period. The primary outcome was fasting SUA level; the secondary outcome was the urinary uric acid to creatinine ratio. Fasting SUA levels in the IP6 group were lower than those in the placebo group (p < 0.05). The urinary uric acid to creatinine ratio did not change between the placebo and IP6 groups (p > 0.05). This study showed that a 2-weeks supplementation period of 600 mg IP6 twice daily can improve fasting SUA levels in hyperuricemic subjects.


Assuntos
Hiperuricemia/tratamento farmacológico , Ácido Fítico/farmacologia , Ácido Úrico/sangue , Adulto , Doenças Assintomáticas , Estudos Cross-Over , Método Duplo-Cego , Jejum , Feminino , Humanos , Masculino , Adulto Jovem
2.
Chemosphere ; 223: 351-357, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784741

RESUMO

At the Department of Energy (DOE) managed Savannah River Site (SRS), uranium and other heavy metals continue to pose threats to the ecosystem health and processes. In the oxic soil of this site, uranium is present primarily as soluble salts of the uranyl ion (i.e., U(VI) or UO22+). Although UO22+ has a strong sorption to the soil, the mobile indigenous bacteria may facilitate its transport. On the contrary, precipitation of UO22+ with phosphate has been found to be an alternative remediation strategy. This research investigated the effects of mobile bacteria and phytate on UO22+ transport at SRS in column experiments. It was discovered that UO22+ can barely be mobilized by de-ionized water but can be significantly transported with the aid of mobile indigenous bacteria. UO22+ had the most facilitated transport observation when it reached equilibrium with the bacteria before the transport. When UO22+ and bacterial were introduced to the soil at the same time or UO22+ was pre-deposited in the soil, the facilitated transport was less pronounced. In the presence of phytate, bacterial-facilitated UO22+ transport was hindered. pH was found to play the key role for UO22+ immobilization in the presence of phytate. The immobilization of UO22+ with the addition of phytate increased with the increase of pH within the pH range of this study because of the impact of pH on the solubility of UO2(OH)2. Phytate promoted UO2--PO43- complex and/or [Ca(UO2)2(PO4)2] formation, leading to enhanced UO22+ immobilization in the SRS soil.


Assuntos
Bactérias/metabolismo , Ácido Fítico/farmacologia , Rios/química , Urânio/análise , Concentração de Íons de Hidrogênio , Imobilização , Fosfatos/química , Solo/química , Solubilidade , Compostos de Urânio/química
3.
Biophys Chem ; 247: 1-12, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30753970

RESUMO

The reaction of 5,5'-dithiobis(2-nitrobenzoate), DTNB, with hemoglobin sulfhydryl groups is linked to three negatively contributing Bohr effect groups: His2ß is present in all avian hemoglobins but absent in some mammalian hemoglobins; His77ß and His143ß are absent in avian but present in nearly all mammalian hemoglobins. To probe the consequences of these differences, we determined the influence of inositol hexakisphosphate (inositol-P6) on the DTNB affinities of avian and mammalian carbonmonoxyhemoglobins. Inositol-P6decreases by two orders of magnitude the DTNB affinity of guinea pig hemoglobin, which has His2ß and the R2 quaternary structure. It decreases, or has no effect on, the DTNB affinities of hemoglobins that have His2ß and whose structures lie along the R2 ⇌ R quaternary equilibrium. Finally, inositol-P6increases by one to two orders of magnitude the DTNB affinities of hemoglobins that lack His2ß. Thus His2ß, DTNB and inositol-P6, in combination, distinguish the R2 from the R quaternary structure.


Assuntos
Carboxihemoglobina/antagonistas & inibidores , Ácido Ditionitrobenzoico/química , Ácido Fítico/farmacologia , Animais , Carboxihemoglobina/química , Galinhas , Cobaias , Concentração de Íons de Hidrogênio , Ácido Fítico/química , Estrutura Quaternária de Proteína
4.
J Environ Pathol Toxicol Oncol ; 38(1): 69-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806292

RESUMO

The risk of cancer development in offspring due to carcinogen exposure during pregnancy is a serious issue. In this study, we explored the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and microRNA-21 (miR-21) in transplacental lung tumorigenesis and its prevention by dietary compound inositol hexaphosphate (IP6) in F1 mice. Balb/c mice were exposed to the N-ethyl-N-nitrosourea (ENU) intraperitoneally on the 17th day of gestation. After weaning, half of the litters were fed with oral 2% IP6. At the end of 30, 120, or 240 days, we did not observe any effect on fetal viability or weight between ENU-exposed and non-exposed litters and the same was true of IP6. Altered expressions of the PI3K/Akt pathway were observed in F1 mice. Further, miR-21 expressions were found to be modulated at the respective time as well, along with the activation of matrix metalloproteinase (MMP-9) and vascular endothelial growth factor expression. Akt activation also enhanced the expression of cyclin D1, cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κBp50), and mammalian target of rapamycin (mTOR). IP6-fed F1 mice showed reduced tumorigenesis along with reduced expression of the PI3K/Akt pathway miR-21 and downstream targets. The PI3K/Akt pathway and miR-21 are involved in transplacental lung tumorigenesis, whereas IP6 seemed to affect lung tumorigenesis by suppressing the expression of the PI3K/Akt pathway in F1 mice.


Assuntos
Neoplasias Pulmonares/metabolismo , MicroRNAs/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Ácido Fítico/farmacologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Feminino , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
5.
Toxins (Basel) ; 11(1)2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30621150

RESUMO

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B1 (FB1) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB1 70 µM, DON 10 µM + FB1 70 µM, DON 10 µM + IP6 5 mM, FB1 70 µM + IP6 5 mM, and DON 10 µM + FB1 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB1 treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB1 exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB1-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB1 alone, or DON and FB1 in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins.


Assuntos
Fumonisinas/toxicidade , Intestinos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ácido Fítico/farmacologia , Tricotecenos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Células Caliciformes/efeitos dos fármacos , Intestinos/patologia , Suínos
6.
Eur J Nutr ; 58(2): 853-864, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29796932

RESUMO

PURPOSE: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. METHODS: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. RESULTS: Fifty-five females completed the study. In the high-phytate-bread group (n = 31) there was no change in any of the iron status biomarkers after 12 weeks of intervention (p > 0.05). In the low-phytate bread group (n = 24) there were significant decreases in both ferritin (mean = 12%; from 32 ± 7 to 27 ± 6 µg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean = 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention. CONCLUSIONS: In Swedish females of reproductive age, 12 weeks of high-phytate wholegrain bread consumption had no effect on iron status. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.


Assuntos
Pão/estatística & dados numéricos , Dieta/métodos , Ferro/sangue , Ácido Fítico/administração & dosagem , Ácido Fítico/sangue , Grãos Integrais/metabolismo , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Ácido Fítico/farmacologia , Valores de Referência , Suécia , Adulto Jovem
7.
Cell Chem Biol ; 26(1): 17-26.e13, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30482680

RESUMO

Clostridium difficile causes increasing numbers of life-threatening intestinal infections. Symptoms associated with C. difficile infection (CDI) are mediated by secreted protein toxins, whose virulence is modulated by intracellular auto-proteolysis following allosteric activation of their protease domains by inositol hexakisphosphate (IP6). Here, we explore the possibility of inactivating the C. difficile toxin B (TcdB) by triggering its auto-proteolysis in the gut lumen prior to cell uptake using gain-of-function small molecules. We anticipated that high calcium concentrations typically found in the gut would strongly chelate IP6, precluding it from pre-emptively inducing toxin auto-proteolysis if administered exogenously. We therefore designed IP6 analogs with reduced susceptibility to complexation by calcium, which maintained allosteric activity at physiological calcium concentrations. We found that oral administration of IP6 analogs attenuated inflammation and promoted survival in mouse models of CDI. Our data provide impetus to further develop small-molecule allosteric triggers of toxin auto-proteolysis as a therapeutic strategy.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Toxinas Bacterianas/antagonistas & inibidores , Infecções por Clostridium/tratamento farmacológico , Clostridium difficile/efeitos dos fármacos , Inflamação/tratamento farmacológico , Ácido Fítico/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Regulação Alostérica/efeitos dos fármacos , Animais , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Infecções por Clostridium/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Camundongos , Ácido Fítico/administração & dosagem , Ácido Fítico/química , Proteólise/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/química
8.
Drug Deliv Transl Res ; 9(1): 53-65, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484258

RESUMO

Phytic acid (PA) has momentous chemotherapeutic potential. Due to the chelate formation and rapid elimination, it is not popular in cancer treatment. The present work was inquested to develop a surface-modified nanoformulation of PA which prevents its speedy elimination and maximizes chemotherapeutic action. Chloroauric acid was reduced with pectin to produce pectin-gold nanoparticles (PGNPs). PGNPs were incubated with PA and jacalin for drug loading and surface modifications, respectively, to form PA-loaded jacalin-pectin-gold nanoparticles (PA-J-PGNPs). Formulation(s) were assessed for various pharmaceutical/pharmacological parameters. To validate the efficacy against colon carcinogenesis, formulation(s) were assessed in 1,2-dimethylhydrazine (DMH)-treated Wistar rats. DMH treatment distorted colonic architecture, oxidative, and hemodynamic parameters, which were favorably restored by PA-J-PGNP administration. To further confirm our deliberations, formulation(s) were also examined against DMH-altered metabolic changes and expression of markers pertaining to cellular proliferation, which was reinstated by PA-J-PGNPs. Our findings establish PA formulation(s) as a promising approach for suppression of colon carcinogenesis.


Assuntos
1,2-Dimetilidrazina/efeitos adversos , Cloretos/química , Neoplasias do Colo/tratamento farmacológico , Compostos de Ouro/química , Metabolômica/métodos , Ácido Fítico/administração & dosagem , Lectinas de Plantas/química , Animais , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Composição de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Fosfatidilinositol 3-Quinases/metabolismo , Ácido Fítico/química , Ácido Fítico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Asian Nat Prod Res ; 21(1): 62-75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29126363

RESUMO

The purpose of this study was to investigate the absorption properties of isorhamnetin (IS), quercetin (QU), and kaempferol (KA) in total flavones of Hippophaë rhamnoides L. (TFH) by an in situ single-pass intestinal perfusion model. The results indicated that IS, QU, and KA in TFH were absorbed site-dependently, and both enterohepatic circulation and intestinal flora could participate in their absorption processes. The absorption mechanisms of IS, QU, and KA in TFH were involved in both passive diffusion and active transport, and the mediation of efflux transporter multidrug resistance-associated proteins (MRPs) should not be neglected.


Assuntos
Flavonoides/farmacocinética , Hippophae/química , Absorção Intestinal , Extratos Vegetais/análise , Animais , Absorção Intestinal/efeitos dos fármacos , Intestinos/microbiologia , Masculino , Perfusão , Ácido Fítico/farmacologia , Ratos , Ratos Sprague-Dawley , Verapamil/farmacologia
10.
Biochem Pharmacol ; 161: 14-25, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30557554

RESUMO

The inositol phosphates, InsP5 and InsP6, have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP6 concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP6 specifically increases platelet aggregate size. This effect is fibrinogen-dependent, since it is inhibited by an antibody that blocks fibrinogen binding to platelets. Furthermore, InsP6 has only an effect on aggregate size of washed platelets when fibrinogen is present, while it has no influence in presence of von Willebrand factor or collagen. By employing blind docking studies we predicted the binding site for InsP6 at the bundle between the γ and ß helical subunit of fibrinogen. Since InsP6 is unable to directly activate platelets and it did not exhibit an effect on thrombin formation or fibrin structure, our data indicate that InsP6 might be a hemostatic agent that is produced by platelets upon stimulation with PLC-activating agonists to promote platelet aggregation by supporting crosslinking of fibrinogen and activated platelets.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Ácido Fítico/metabolismo , Ácido Fítico/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Plaquetas/química , Fibrinogênio/metabolismo , Humanos , Ácido Fítico/química , Agregação Plaquetária/fisiologia , Estrutura Secundária de Proteína
11.
Br J Clin Pharmacol ; 84(12): 2867-2876, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30280390

RESUMO

AIMS: SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS: This is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation. RESULTS: Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 ± 21.0%, P < 0.001, 95% CI, -32.4 to 49.7). CONCLUSION: The results from this study showed acceptable safety and tolerability, and lack of significant dialysability of IV SNF472. It is a potential novel treatment for cardiovascular calcification in end-stage renal disease and calciphylaxis warranting further human studies.


Assuntos
Falência Renal Crônica/terapia , Ácido Fítico/efeitos adversos , Diálise Renal/efeitos adversos , Calcificação Vascular/prevenção & controle , Adulto , Idoso , Cálcio/metabolismo , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Ácido Fítico/farmacocinética , Ácido Fítico/farmacologia
12.
Int J Oncol ; 53(4): 1625-1632, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066850

RESUMO

Inositol hexaphosphate (IP6), also known as phytic acid, has been shown to exhibit anticancer effects in a number of preclinical tumor models. IP6 decreases proliferation by arresting cells in the G0/G1 phase, inhibits iron-mediated oxidative reactions, enhances differentiation and stimulates apoptosis. The present study attempted to characterize the effect of IP6 on the migration and adhesion of colon cancer SW620 cells. IP6 was assessed at concentrations of 0.2 and 1 mM during 12, 24 and 48 h of exposure. Migration ability was measured with the real-time xCELLigence Real-Time Cell Analyzer Dual Purpose system. The expression of mRNA and proteins involved in migration and cancer progression [epithelial cell adhesion molecule, intercellular adhesion molecule-1, ß-catenin, N-cadherin, E-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9] was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The changes in the expression and subcellular localization of E-cadherin were determined by indirect immunofluorescence. IP6 induced a decrease in the migration ability of the tested SW620 cell line. IP6-treated cells also showed decreased expression of N-cadherin, increased levels of E-cadherin and decreased expression of MMP-2 and MMP-9. These results indicated that IP6 has potential to modulate the migration ability and expression of markers associated with invasion in SW620 cells; however, further analysis is necessary to obtain a detailed understanding of the mechanism of action.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Ácido Fítico/farmacologia , Antineoplásicos/uso terapêutico , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Progressão da Doença , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Invasividade Neoplásica/prevenção & controle , Ácido Fítico/uso terapêutico
13.
Nutr Rev ; 76(11): 793-804, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010865

RESUMO

Plant-based diets in low-income countries (LICs) have a high content of phytic acid (myo-inositol hexaphosphate [InsP6]) and associated magnesium, potassium, and calcium salts. Together, InsP6 acid and its salts are termed "phytate" and are potent inhibitors of iron and zinc absorption. Traditional food processing can reduce the InsP6 content through loss of water-soluble phytate or through phytase hydrolysis to lower myo-inositol phosphate forms that no longer inhibit iron and zinc absorption. Hence, some processing practices can reduce the need for high-dose iron fortificants in plant-based diets and alleviate safety concerns. Dietary phytate-to-iron and phytate-to-zinc molar ratios are used to estimate iron and zinc bioavailability and to identify dietary iron and zinc requirements according to diet type. The European Food Safety Authority has set adult dietary zinc requirements for 4 levels of phytate intake, highlighting the urgent need for phytate food composition data. Such data will improve the ability to estimate the prevalence of inadequate zinc intakes in vulnerable groups in LICs, which will facilitate implementation of targeted policies to alleviate zinc deficiency.


Assuntos
Ferro na Dieta/farmacocinética , Necessidades Nutricionais/efeitos dos fármacos , Ácido Fítico/farmacologia , Plantas Comestíveis/química , Zinco/farmacocinética , Adulto , Disponibilidade Biológica , Países em Desenvolvimento , Dieta/métodos , Feminino , Manipulação de Alimentos , Humanos , Masculino , Política Nutricional , Estado Nutricional
14.
Mater Sci Eng C Mater Biol Appl ; 91: 218-227, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033249

RESUMO

To improve the corrosion resistance and bioactivity of AZ31 magnesium alloy, a crack-free magnesium phytic acid/apatite composite coating was synthesized on AZ31 substrate via chemical conversion deposition and followed a rapid microwave assisted treatment. The influences of pH values of the microwave solution on the morphology, composition and corrosion resistance properties of the composite coating were investigated. An apatite coating with bilayer structure was completely covered the magnesium phytic acid conversion coating after microwave radiation in the solution of pH 6.5, which reached the thickness of ~7.0 µm. During the electrochemical and immersion tests in simulated body fluid (SBF), the samples with composite coating exhibited a remarkably improved corrosion resistance, slower degradation rate and rapid inducing of Ca-P apatite deposition, suggesting that the composite coating could provide a long-time protection for substrates and promote the bioactivity of AZ31 magnesium alloys. Moreover, after 5 days of incubation, the composite coating showed non-cytotoxicity, good osteoblast adhesion and proliferation.


Assuntos
Ligas , Apatitas , Materiais Revestidos Biocompatíveis , Magnésio , Micro-Ondas , Ácido Fítico , Ligas/química , Ligas/farmacologia , Animais , Apatitas/química , Apatitas/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Magnésio/química , Magnésio/farmacologia , Teste de Materiais , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Ácido Fítico/química , Ácido Fítico/farmacologia
15.
Sci Rep ; 8(1): 9619, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29941991

RESUMO

Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Ácido Fítico/farmacologia , Idoso , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Fítico/efeitos adversos , Segurança
16.
Br J Nutr ; 120(2): 121-130, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29947321

RESUMO

Phytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and inflammation processes are involved in the development and progression of CRC. In the present study, we evaluated the effect of PA on the intestinal mucosal barrier and proinflammatory cytokines. After a 1-week acclimatisation period, sixty Wistar male rats were divided into the following five groups, with twelve rats per group: the control group (CG), model group (MG), low-PA-dose group (0·25 g/kg per d), middle-PA-dose group (0·5 g/kg per d), and high-PA-dose group (1 g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight was injected weekly to induce CRC for 18 weeks. We examined the expression of genes related to the intestinal mucosal barrier in the model. The results demonstrated that tumour incidence was decreased following PA treatment. The mRNA and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin in the MG were significantly lower than those in the CG (P<0·05). The mRNA and protein expression of claudin-1 in the MG were significantly higher than those in the CG (P<0·05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E-cadherin, and diminished the mRNA and protein expression of claudin-1. Furthermore, PA decreased serum levels of proinflammatory cytokines, which included TNF-α, IL-1ß and IL-6. In conclusion, this study suggests that PA has favourable effects on the intestinal mucosal barrier and may reduce serum proinflammatory cytokine levels.


Assuntos
Neoplasias Colorretais/sangue , Citocinas/sangue , Mucosa Intestinal/efeitos dos fármacos , Ácido Fítico/farmacologia , 1,2-Dimetilidrazina/química , Animais , Peso Corporal , Caderinas/metabolismo , Claudina-1/metabolismo , Colo/metabolismo , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Inflamação , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Ácido Láctico/sangue , Lipopolissacarídeos/sangue , Masculino , Mucina-2/metabolismo , Fenótipo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator Trefoil-3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
J Dent ; 73: 24-31, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29604316

RESUMO

OBJECTIVES: To compare and explore the dose-response of phytate-containing 1150 ppm fluoride toothpastes on model caries lesions and to determine the impact of zinc ions. METHODS: This was a single-centre, randomised, blinded (examiner/laboratory analyst), six-treatment, four-period crossover, in situ study in adults with a removable bilateral maxillary partial denture. Study treatments were toothpastes containing: 0.425% phytate/F; 0.85% phytate/F; 0.85% phytate/Zn/F; F-only; Zn/F and a 0% F placebo. Where present, F was 1150 ppm as NaF; Zn was 0.3% as ZnCl2. Human enamel specimens containing early-stage, surface-softened (A-lesions) or more advanced, subsurface (B-lesions) caries lesions were placed into the buccal flanges of participants' modified partial denture (one of each lesion type per side). A-lesions were removed after 14 days of twice-daily treatment use; B-lesions were removed after a further 14 days. A-lesions were analysed for surface microhardness recovery. Both lesion types were analysed by transverse microradiography and for enamel fluoride uptake, with B-lesions additionally analysed by quantitative light-induced fluorescence. Comparison was carried out using an analysis of covariance model. RESULTS: Statistically significant differences between 1150 ppm F and the placebo toothpastes (p < 0.05) were shown for all measures, validating the model. No differences between fluoride toothpastes were observed for any measure with little evidence of a dose-response for phytate. Study treatments were generally well-tolerated. CONCLUSIONS: Results suggest phytate has little impact on fluoride's ability to promote early-stage lesion remineralisation or prevent more advanced lesion demineralisation in this in situ caries model. Similarly, results suggest zinc ions do not impair fluoride efficacy. CLINICAL SIGNIFICANCE: Toothpastes may contain therapeutic or cosmetic agents that could interfere with fluoride's caries prevention efficacy. The present in situ caries study has demonstrated that phytate, added to provide enhanced extrinsic stain removal/prevention, and zinc, added to inhibit malodour, do not impair fluoride efficacy.


Assuntos
Cárie Dentária/prevenção & controle , Fluoretos/uso terapêutico , Ácido Fítico/farmacologia , Cremes Dentais/uso terapêutico , Zinco/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cariostáticos/uso terapêutico , Esmalte Dentário/efeitos dos fármacos , Feminino , Fluoretos/química , Humanos , Indiana , Masculino , Microrradiografia/métodos , Pessoa de Meia-Idade , Ácido Fítico/química , Fluoreto de Sódio/uso terapêutico , Remineralização Dentária/métodos , Resultado do Tratamento , Adulto Jovem , Zinco/química
18.
Clin Oral Investig ; 22(7): 2543-2552, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29423713

RESUMO

OBJECTIVE: The objective of this work was to evaluate effects of a dentifrice containing sodium fluoride (1150 ppm F) and the organic polyphosphate phytate (0.85% w/w of the hexa-sodium salt) on in situ remineralisation of early enamel erosive lesions and resistance to subsequent demineralisation. MATERIALS AND METHODS: Subjects (n = 62) wore palatal appliances holding eight bovine enamel specimens with pre-formed erosive lesions. They brushed their natural teeth with the phytate test dentifrice (TD); a positive control dentifrice (PC, 1150 ppm fluoride as NaF); a reference dentifrice (RD, disodium pyrophosphate + 1100 ppm fluoride as NaF) or a negative control dentifrice (NC, fluoride-free) in a randomised, double-blind, crossover design. Specimens were removed at 2, 4 and 8 h post-brushing and exposed to an ex vivo acid challenge. Surface microhardness (Knoop) was measured at each stage. The primary efficacy variable was relative erosion resistance (RER); other variables included the surface microhardness recovery (SMHR), acid resistance ratio (ARR) and enamel fluoride uptake (EFU). RESULTS: After 4 h, the results for RER, ARR and EFU were in the order PC > TD = RD > NC with PC > TD = RD = NC for SMHR. Results at 2 and 8 h were generally consistent with the 4 h data. Mineralisation progressed over time. Dentifrices were generally well-tolerated. CONCLUSIONS: In this in situ model, addition of phytate or pyrophosphate to a fluoride dentifrice inhibited the remineralising effect of fluoride. Both formulations still delivered fluoride to the enamel and inhibited demineralisation, albeit to a lesser extent than a polyphosphate-free dentifrice. CLINICAL RELEVANCE: Addition of phytate or pyrophosphate to a fluoride dentifrice may reduce its net anti-erosive properties.


Assuntos
Dentifrícios/farmacologia , Ácido Fítico/farmacologia , Fluoreto de Sódio/farmacologia , Erosão Dentária/prevenção & controle , Remineralização Dentária/métodos , Adolescente , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Dureza , Humanos , Masculino , Pessoa de Meia-Idade , Propriedades de Superfície , Resultado do Tratamento
19.
Food Chem ; 252: 1-8, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29478519

RESUMO

Bioavailability of food nutrients can be reduced in the presence of antinutrients such as phytates and tannins. This work aimed to study bovine serum albumin binding to phytic acid and tannic acid, and its influence on in vitro protein digestibility. The effect of autoclaving and boiling on protein digestibility and the microstructure of complexes was also evaluated. Results showed that high ionic strength promotes greater affinity between tannic acid and bovine serum albumin, and decreases in vitro protein digestibility. For phytic acid and bovine serum albumin, the opposite behavior is observed because interactions are governed by electrostatic forces. A rise in temperature above that causing denaturation of the protein favors its interaction with phytic acid, and disfavors that with tannic acid, probably due to different protein binding site exposure. For both antinutrients, heating treatment increased protein hydrolysis, the size of complexes and their fragility.


Assuntos
Digestão/efeitos dos fármacos , Temperatura Alta , Ácido Fítico/metabolismo , Ácido Fítico/farmacologia , Soroalbumina Bovina/metabolismo , Taninos/metabolismo , Taninos/farmacologia , Animais , Bovinos , Concentração Osmolar , Ligação Proteica
20.
Curr Microbiol ; 75(7): 849-856, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29464362

RESUMO

The antibiotic resistance in bacteria responsible for causing community and health care-associated infection displayed a major threat to global health. Use of broad-spectrum antibiotics for the treatment of various ailments poses serious side effects. In the present research, we investigated the combined role of 2% phytic acid with 2% methanolic seed extract of Syzygium cumini and 0.5% sodium chloride for inhibition of Bacillus subtilis and Pseudomonas aeruginosa and found it to be efficient over B. subtilis. The zone of inhibition by present mixture was found to be 2.9 ± 0.0004 and 1.9 ± 0.0006 cm against Bacillus subtilis and P. aeruginosa in comparison to individual component. Mixture was found more potent against B. subtilis and selected for further study. The underlying mechanism involved in inhibitory action of this mixture was determined by Scanning electron microscope, DNA fragmentation and propidium iodide staining. Scanning electron microscopy revealed that inhibition of B. subtilis by this mixture is mainly due to the disruption of bacterial cell membrane, leakage of internal cellular content which ultimately leads to the death of bacterial cells. DNA fragmentation showed apoptotic hallmark through degradation caused by mixture against B. subtilis at various time intervals. Likewise, PI staining also revealed the disruption of bacterial membrane by the mixture as the PI gives fluorescence after binding with DNA. The present study concludes that inhibitory potential of this mixture is mainly due to disruption of bacterial cell membrane, degradation of DNA and creation of pores in the membrane. The mixture could be used for inhibition of food pathogen B. subtilis.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Ácido Fítico/farmacologia , Sementes/química , Syzygium/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento
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