Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Eur J Pharm Biopharm ; 158: 410-416, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33271303

RESUMO

Lipid mesophases are lyotropic liquid crystalline systems which differ from liposomes and other globular aggregates in dilute regimes due to their inner ordering. It is known that natural lipids enable to obtain a rich variety of nanosystems and many of them have been proposed as delivery agents for bioactive compounds. Due to their packing parameters, several classes of lipids found in natural sources are able to self-assemble into nonlamellar structures. Among lipids occurring in plants and algae, triglycerides display this tendency. In the present study we examine new nanosystems built with lipids extracted from the marine microalga Nannochloropsis sp and their use as carriers for lipophilic antioxidants. The antioxidants studied, curcumin and tocopherol were encapsulated with high rate in the carriers. The physico-chemical characterization of plain and loaded vectors showed their structure and localization site, as well as the structure-functionality relationship related to potential drug delivery. The results show that the cargo molecules play an active role in driving the interactions which characterize the overall structure of the aggregates. The systems studied showed several coexisting mesophases, the most predominant structure being of cubic symmetry.


Assuntos
Antioxidantes/administração & dosagem , Portadores de Fármacos/química , Lipídeos/química , Cristais Líquidos/química , Microalgas/química , Antioxidantes/farmacocinética , Curcumina/administração & dosagem , Curcumina/farmacocinética , Portadores de Fármacos/isolamento & purificação , Composição de Medicamentos/métodos , Lipídeos/isolamento & purificação , Estrutura Molecular , Tocoferóis/administração & dosagem , Tocoferóis/farmacocinética
2.
J Nutr ; 150(2): 222-230, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495894

RESUMO

BACKGROUND: Vitamin E α-, γ-, or δ-tocopherol (αT, γT, δT) and γ- or δ-tocotrienol (γTE, δTE) are metabolized to hydroxychromanols and carboxychromanols including 13'-carboxychromanol (13'-COOH), 11'-COOH, and carboxyethyl hydroxychroman (CEHC), some of which have unique bioactivities compared with the vitamers. However, the bioavailability of these metabolites has not been well characterized. OBJECTIVE: We investigated the pharmacokinetics (PK) of vitamin E forms and metabolites in rats. METHODS: Six-week-old male Wistar rats received 1-time gavage of γT-rich tocopherols (50 mg/kg) containing γT/δT/αT (57.7%, 21.9%, and 10.9%, respectively) or δTE-rich tocotrienols (35 mg/kg) containing δTE/γTE (8:1). We quantified the time course of vitamin E forms and metabolites in the plasma and their 24-h excretion to the urine and feces. The general linear model repeated measure was used for analyses of the PK data. RESULTS: In the rats' plasma, Cmax of γT or δTE was 25.6 ± 9.1 µM (Tmax = 4 h) or 16.0 ± 2.3 µM (Tmax = 2 h), respectively, and sulfated CEHCs and sulfated 11'-COOHs were the predominant metabolites with Cmax of 0.4-0.5 µM (Tmax ∼5-7 h) or ∼0.3 µM (Tmax at 4.7 h), respectively. In 24-h urine, 2.7% of γT and 0.7% of δTE were excreted as conjugated CEHCs. In the feces, 17-45% of supplemented vitamers were excreted as unmetabolized forms and 4.9-9.2% as unconjugated carboxychromanols, among which 13'-COOHs constituted ∼50% of total metabolites and the amount of δTE-derived 13'-COOHs was double that of 13'-COOH derived from γT. CONCLUSIONS: PK data of vitamin E forms in rats reveal that γT, δT, γTE, and δTE are bioavailable in the plasma and are mainly excreted as unmetabolized forms and long-chain metabolites including 13'-COOHs in feces, with more metabolites from tocotrienols than from tocopherols.


Assuntos
Cromanos/metabolismo , Fezes , Tocoferóis/farmacocinética , Tocotrienóis/farmacocinética , Animais , Disponibilidade Biológica , Masculino , Ratos , Ratos Wistar
3.
Nutrients ; 11(10)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569705

RESUMO

The ultimate health benefits of peanuts and tree nuts partially depend on the effective gastrointestinal delivery of their phytochemicals. The chemical composition and in vitro bioaccessibility of tocopherols, tocotrienols and phenolic compounds from peanuts and seven tree nuts were evaluated by analytical and chemometric methods. Total fat and dietary fiber (g 100 g-1) ranged from 34.2 (Emory oak acorn) to 72.5 (pink pine nut; PPN) and from 1.2 (PPN) to 22.5 (pistachio). Samples were rich in oleic and linoleic acids (56-87 g 100 g-1 oil). Tocopherols and tocotrienols (mg·kg-1) ranged from 48.1 (peanut) to 156.3 (almond) and 0 (almond, pecan) to 22.1 (PPN) and hydrophilic phenolics from 533 (PPN) to 12,896 (Emory oak acorn); flavonoids and condensed tannins (mg CE.100 g-1) ranged from 142 (white pine nut) to 1833 (Emory oak acorn) and 14 (PPN) to 460 (Emory oak acorn). Three principal components explained 90% of the variance associated with the diversity of antioxidant phytochemicals in samples. In vitro bioaccessibility of tocopherols, tocotrienols, hydrophilic phenolics, flavonoids, and condensed tannins ranged from 11-51%, 16-79%, 25-55%, 0-100%, and 0-94%, respectively. Multiple regression analyses revealed a potential influence of dietary fiber, fats and/or unsaturated fatty acids on phytochemical bioaccessibility, in a structure-specific manner.


Assuntos
Antioxidantes/farmacocinética , Nozes/química , Compostos Fitoquímicos/farmacocinética , Disponibilidade Biológica , Flavonoides/farmacocinética , Humanos , Hidroxibenzoatos/farmacocinética , Análise de Componente Principal , Proantocianidinas/farmacocinética , Análise de Regressão , Tocoferóis/farmacocinética , Tocotrienóis/farmacocinética
4.
Colloids Surf B Biointerfaces ; 175: 281-290, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30551015

RESUMO

Biodegradable polymer based 'controlled release packaging' technology has ability to release packaging actives in controlled manner to prolong the food shelf-life. Currently available systems are not sufficiently capable of releasing multiple actives in sustainable fashion. Hence, the purpose of this study was to develop dual actives (antioxidant and antibacterial) loaded multilayered microparticles in one step and to release them at rates suitable for long-term inhibition of bacterial growth as well as lipid oxidation in food. In order to achieve this goal, 2 kinds of multilayered polymer particles made up of PLLA (Poly(l-lactic acid)) and PLGA (Poly(dl-lactic-co-glycolic acid) with varying viscosity were developed using emulsion solvent evaporation method. Surprisingly, low viscous PLGA resulted tri-layered particles (PLGA/PLLA/PLGA: shell/middle/core) instead of bi-layered (PLGA/PLLA: shell/core) particles as observed for high viscous PLGA. The mechanism of formation of tri-layered particles was investigated in detail. The outermost layer consisted of relatively more hydrophilic polymer PLGA along with benzoic acid (antibacterial) and the inner core comprised of hydrophobic polymer PLLA and tocopherol (antioxidant). Release study demonstrated that release rate of dual actives were significantly accelerated from tri-layered particles in comparison to bi-layered one and their release profiles can be well explained with the help of Ridger-Peppas model. Both sets of particles exhibited long-term antibacterial (against both Escherichia coli and Staphylococcus aureus) as well as antioxidant effect over a period of 60 days. The results show for the first time the feasibility of using multilayered microparticles to prolong the food shelf-life by simultaneous release of multiple actives.


Assuntos
Ácido Benzoico/farmacocinética , Liberação Controlada de Fármacos , Armazenamento de Alimentos/métodos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tocoferóis/farmacocinética , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Ácido Benzoico/química , Ácido Benzoico/farmacologia , Emulsões/química , Escherichia coli/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Reprodutibilidade dos Testes , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Fatores de Tempo , Tocoferóis/química , Tocoferóis/farmacologia
5.
Food Res Int ; 114: 251-257, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30361023

RESUMO

Nanoparticles were fabricated by adsorbing gum arabic (GA) on zein nanoparticles by antisolvent precipitation. The most stable mass ratio of zein:GA was 1:1.5 with a stable zeta-potential (-32.8 mV) in a pH range of 3.0-9.0. The surface hydrophobicity of zein-GA nanoparticles indicated formation of a stable structure through electrostatic attraction at a pH range of 3.0-6.0 and hydrophobic interaction at pH 7.0-9.0. The FTIR spectrogram showed an additional role of hydrogen bonds to promote the adsorption of GA on zein nanoparticles. Tocopherol (TOC) was encapsulated within the prepared zein-GA nanoparticles with a high loading capacity. The presence of GA not only prevented the precipitation of zein nanoparticles but also controlled the release of TOC from zein-GA nanoparticles during in vitro gastrointestinal digestion. Zein-GA biopolymer nanoparticles can be stably fabricated in a wide pH range for applications in the food and pharmacy industries.


Assuntos
Goma Arábica/química , Nanopartículas/química , Tocoferóis , Zeína/química , Digestão , Composição de Medicamentos , Humanos , Modelos Biológicos , Tamanho da Partícula , Tocoferóis/química , Tocoferóis/farmacocinética
6.
Clin Cancer Res ; 24(11): 2585-2593, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29514842

RESUMO

Purpose: Currently, <50% of high-risk pediatric solid tumors like neuroblastoma can be cured, and many survivors experience serious or life-threatening toxicities, so more effective, less toxic therapy is needed. One approach is to target drugs to tumors using nanoparticles, which take advantage of the enhanced permeability of tumor vasculature.Experimental Design: SN38, the active metabolite of irinotecan (CPT-11), is a potent therapeutic agent that is readily encapsulated in polymeric nanoparticles. Tocopherol oxyacetate (TOA) is a hydrophobic mitocan that was linked to SN38 to significantly increase hydrophobicity and enhance nanoparticle retention. We treated neuroblastomas with SN38-TOA nanoparticles and compared the efficacy with the parent prodrug CPT-11 using a mouse xenograft model.Results: Nanoparticle treatment induced prolonged event-free survival (EFS) in most mice, compared with CPT-11. This was shown for both SH-SY5Y and IMR-32 neuroblastoma xenografts. Enhanced efficacy was likely due to increased and sustained drug levels of SN38 in the tumor compared with conventional CPT-11 delivery. Interestingly, when recurrent CPT-11-treated tumors were re-treated with SN38-TOA nanoparticles, the tumors transformed from undifferentiated neuroblastomas to maturing ganglioneuroblastomas. Furthermore, these tumors were infiltrated with Schwann cells of mouse origin, which may have contributed to the differentiated histology.Conclusions: Nanoparticle delivery of SN38-TOA produced increased drug delivery and prolonged EFS compared to conventional delivery of CPT-11. Also, lower total dose and drug entrapment in nanoparticles during circulation should decrease toxicity. We propose that nanoparticle-based delivery of a rationally designed prodrug is an attractive approach to enhance chemotherapeutic efficacy in pediatric and adult tumors. Clin Cancer Res; 24(11); 2585-93. ©2018 AACR.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Irinotecano/administração & dosagem , Nanopartículas , Pró-Fármacos/administração & dosagem , Tocoferóis/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Injeções Intralesionais , Irinotecano/farmacocinética , Camundongos , Nanopartículas/química , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Pró-Fármacos/farmacocinética , Recidiva , Retratamento , Taxa de Sobrevida , Distribuição Tecidual , Tocoferóis/farmacocinética , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Am J Clin Nutr ; 106(4): 1041-1051, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28814399

RESUMO

Background: Previously, we showed that vegetable oil is necessary for carotenoid absorption from salad vegetables. Research is needed to better define the dose effect and its interindividual variation for carotenoids and fat-soluble vitamins.Objective: The objective was to model the dose-response relation between the amount of soybean oil in salad dressing and the absorption of 1) carotenoids, phylloquinone, and tocopherols in salad vegetables and 2) retinyl palmitate formed from the provitamin A carotenoids.Design: Women (n = 12) each consumed 5 vegetable salads with salad dressings containing 0, 2, 4, 8, or 32 g soybean oil. Blood was collected at selected time points. The outcome variables were the chylomicron carotenoid and fat-soluble vitamin area under the curve (AUC) and maximum content in the plasma chylomicron fraction (Cmax). The individual-specific and group-average dose-response relations were investigated by fitting linear mixed-effects random coefficient models.Results: Across the entire 0-32-g range, soybean oil was linearly related to the chylomicron AUC and Cmax values for α-carotene, lycopene, phylloquinone, and retinyl palmitate. Across 0-8 g of soybean oil, there was a linear increase in the chylomicron AUC and Cmax values for ß-carotene. Across a more limited 0-4-g range of soybean oil, there were minor linear increases in the chylomicron AUC for lutein and α- and total tocopherol. Absorption of all carotenoids and fat-soluble vitamins was highest with 32 g oil (P < 0.002). For 32 g oil, the interindividual rank order of the chylomicron AUCs was consistent across the carotenoids and fat-soluble vitamins (P < 0.0001).Conclusions: Within the linear range, the average absorption of carotenoids and fat-soluble vitamins could be largely predicted by the soybean oil effect. However, the effect varied widely, and some individuals showed a negligible response. There was a global soybean oil effect such that those who absorbed more of one carotenoid and fat-soluble vitamin also tended to absorb more of the others. This trial was registered at clinicaltrials.gov as NCT02867488.


Assuntos
Carotenoides/farmacocinética , Dieta , Absorção Intestinal/efeitos dos fármacos , Óleo de Soja/administração & dosagem , Verduras/química , Vitamina A/análogos & derivados , Vitaminas/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Carotenoides/sangue , Quilomícrons , Diterpenos , Relação Dose-Resposta a Droga , Feminino , Humanos , Luteína/sangue , Luteína/farmacocinética , Licopeno , Modelos Biológicos , Ésteres de Retinil , Solubilidade , Óleo de Soja/farmacologia , Tocoferóis/sangue , Tocoferóis/farmacocinética , Vitamina A/sangue , Vitamina K 1/sangue , Vitamina K 1/farmacocinética , Vitaminas/sangue , Adulto Jovem
9.
PLoS One ; 12(2): e0171662, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28192494

RESUMO

Ferulic acid (FA) and tocopherol (Toc) loaded solid lipid nanoparticles (SLN) were prepared by a hot homogenisation method. The particle size distribution, zeta potential and melting behaviour of the SLN as well as the stability, encapsulation efficiency and radical scavenging activity of FA and Toc in the SLN were analysed. The different formulations containing up to 2.8 mg g-1 of FA or Toc were stable during at least 15 weeks of storage at room temperature. Despite partial degradation and / or release of FA and Toc during storage, significant radical scavenging activity was maintained. DSC measurements and radical scavenging tests after different time periods revealed that the re-structuring of the lipid matrix was connected to the enhanced antioxidant activity of Toc but did not affect the activity of FA.


Assuntos
Antioxidantes/administração & dosagem , Ácidos Cumáricos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Lipídeos/química , Nanopartículas/química , Antioxidantes/química , Antioxidantes/farmacocinética , Varredura Diferencial de Calorimetria , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacocinética , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacocinética , Humanos , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula , Temperatura , Tocoferóis/administração & dosagem , Tocoferóis/química , Tocoferóis/farmacocinética , Difração de Raios X
10.
Mini Rev Med Chem ; 17(12): 1039-1052, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27457214

RESUMO

OBJECTIVE: This review examines various aspects of vitamin E, both in plant metabolism and with regard to its importance for human health. Vitamin E is the collective name of a group of lipidsoluble compounds, chromanols, which are widely distributed in the plant kingdom. Their biosynthetic pathway, intracellular distribution and antioxidant function in plants are well recognized, although their other functions are also considered. CONCLUSION: Analytical methods for the determination of vitamin E are discussed in detail. Furthermore, the vitamin E metabolism and its antioxidant action in humans are described. Other nonantioxidant functions of vitamin E are also presented, such as its anti-inflammatory effects, role in the prevention of cardiovascular diseases and cancer, as well as its protective functions against neurodegenerative and other diseases.


Assuntos
Plantas/química , Vitamina E/biossíntese , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Antioxidantes/farmacocinética , Cromatografia Líquida de Alta Pressão , Humanos , Sistema Imunitário/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Plantas/metabolismo , Tocoferóis/análise , Tocoferóis/química , Tocoferóis/metabolismo , Tocoferóis/farmacocinética , Tocotrienóis/análise , Tocotrienóis/química , Tocotrienóis/metabolismo , Tocotrienóis/farmacocinética , Vitamina E/análise , Vitamina E/farmacocinética , Vitamina E/uso terapêutico
11.
BMC Cancer ; 16: 199, 2016 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-26957307

RESUMO

BACKGROUND: Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. METHODS: Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. RESULTS: Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. CONCLUSION: We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer.


Assuntos
Tocoferóis/farmacocinética , Tocoferóis/toxicidade , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Biópsia , Contagem de Células Sanguíneas , Análise Química do Sangue , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Cães , Feminino , Lisina , Masculino , Sais , Fatores de Tempo , Tocoferóis/administração & dosagem , Tocoferóis/química , Testes de Toxicidade , Toxicocinética , Urinálise
12.
JPEN J Parenter Enteral Nutr ; 40(5): 672-81, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-25168593

RESUMO

BACKGROUND: Tocopherols and tocotrienols possess vitamin E activity and function as the major lipid-soluble antioxidants in the human body. Commercial lipid emulsions are composed of different oils and supply different amounts of vitamin E. The objective of this study was to measure all 8 vitamin E homologs within 4 different commercial lipid emulsions and evaluate their distribution in guinea pig tissues. MATERIALS AND METHODS: The distribution of vitamin E homologs within plasma and guinea pig tissues was determined using a high-performance liquid chromatography (HPLC) system. Lipid hydroperoxides in lipid emulsions were determined using a commercial kit (Cayman Chemical Company, Ann Arbor, MI), and malondialdehyde tissue levels were determined using an HPLC system. RESULTS: The lipid emulsions contained variable amounts of tocopherols, which were significantly different between emulsions. Tocotrienols were present at very low concentrations (≤0.3%). We found no correlation between the amount of vitamin E present in the lipid emulsions and lipid peroxidation. Hydroperoxides were the lowest with an olive oil-based emulsion and highest with a fish oil emulsion. The predominant vitamin E homolog in guinea pig tissues was α-tocopherol. No tissues had detectable levels of tocotrienols. Vitamin E levels (primarily α-tocopherol and γ-tocopherol) were highly variable among organ tissues. Plasma levels were a poor reflection of most tissue levels. CONCLUSION: Vitamin E levels within different lipid emulsions and plasma/tissues are highly variable, and no one tissue or plasma sample serves as a good proxy for levels in other tissues. All study emulsions were well tolerated and did not significantly increase systemic lipid peroxidation.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Nutrição Parenteral , Tocoferóis/farmacocinética , Tocotrienóis/farmacocinética , Animais , Antioxidantes , Emulsões Gordurosas Intravenosas/análise , Óleos de Peixe , Cobaias , Peroxidação de Lipídeos , Azeite de Oliva , Distribuição Tecidual , Tocoferóis/análise , Tocoferóis/sangue , Tocotrienóis/análise , alfa-Tocoferol/análise , alfa-Tocoferol/sangue
13.
Mol Biol Rep ; 41(11): 7671-81, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25098603

RESUMO

Tocopherols are micronutrients with antioxidant properties. They are synthesized by photosynthetic bacteria and plants, and play important roles in animal and human nutrition. In this study, we isolated a new rice mutant line with elevated tocopherol content (MRXII) from an in vitro mutagenized population induced by gamma irradiation. The mutant exhibited greater seed longevity than the control, indicating a crucial role for tocopherols in maintaining viability during quiescence, and displayed faster seedling growth during the early growth stage. To study the molecular mechanism underlying vitamin E biosynthesis, we examined the expression patterns of seven rice genes encoding vitamin E biosynthetic enzymes. Accumulation levels of the OsVTE2 transcript and OsVTE2 protein in the MRXII mutant were significantly higher than in the control. Sequence analysis revealed that the MRXII mutant harbored a point mutation in the OsVTE2 promoter region, which resulted in the generation of MYB transcription factor-binding cis-element. These results help identify the promoter regions that regulate OsVTE2 transcription, and offer insights into the regulation of tocopherol content.


Assuntos
Vias Biossintéticas/fisiologia , Raios gama , Oryza/genética , Oryza/metabolismo , Sementes/metabolismo , Tocoferóis/farmacocinética , Vitamina E/biossíntese , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Sequência de Bases , Vias Biossintéticas/genética , Cromatografia Líquida de Alta Pressão , Primers do DNA/genética , Dados de Sequência Molecular , Oryza/efeitos da radiação , Reação em Cadeia da Polimerase em Tempo Real , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Análise de Sequência de DNA
14.
J. physiol. biochem ; 70(2): 385-395, jun. 2014.
Artigo em Inglês | IBECS | ID: ibc-122960

RESUMO

A diet high in fructose (HFr) induces insulin resistance in animals. Free radicals are involved in the pathogenesis of HFr-induced insulin resistance. Carnosine (CAR) is a dipeptide with antioxidant properties. We investigated the effect of CAR alone or in combination with α-tocopherol (CAR + TOC) on HFr-induced insulin-resistant rats. Rats fed with HFr containing 60 % fructose received CAR (2 g/L in drinking water) with/without TOC (200 mg/kg, i.m. twice a week) for 8 weeks. Insulin resistance, serum lipids, inflammation markers, hepatic lipids, lipid peroxides, and glutathione (GSH) levels together with glutathione peroxidase (GSH-Px) and superoxide dismutase 1 (CuZnSOD; SOD1) activities and their protein expressions were measured. Hepatic histopathological examinations were performed. HFr was observed to cause insulin resistance, inflammation and hypertriglyceridemia, and increased triglyceride and lipid peroxide levels in the liver. GSH-Px activity and expression decreased, but GSH levels and SOD1 activity and expression did not alter in HFr rats. Hepatic marker enzyme activities in serum increased and marked macro- and microvesicular steatosis were seen in the liver. CAR treatment did not alter insulin resistance and hypertriglyceridemia, but it decreased steatosis and lipid peroxidation without any change in the antioxidant system of the liver. However, CAR + TOC treatment decreased insulin resistance, inflammation, hepatic steatosis, and lipid peroxidation and increased GSH-Px activity and expression in the liver. Our results may indicate that CAR + TOC treatment is more effective to decrease HFr-induced insulin resistance, inflammation, hepatic steatosis, and dysfunction and pro-oxidant status in rats than CAR alone


Assuntos
Animais , Ratos , Carnosina/farmacocinética , Tocoferóis/farmacocinética , Fígado Gorduroso/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Estresse Oxidativo , Inflamação/tratamento farmacológico , Substâncias Protetoras/farmacocinética , Modelos Animais de Doenças
15.
Artigo em Inglês | MEDLINE | ID: mdl-23872319

RESUMO

There has been much recent interest from both applied and basic scientists in the broad series of benefits that animals reap from acquiring high concentrations of dietary antioxidants, such as carotenoids and vitamins (e.g., vitamin E, or tocopherol). Most attention has been paid to separate effects of these compounds on, for example, coloration, health state, development, and vision, but because of possible interactions between these lipid-soluble molecules, we are in need of more studies that co-manipulate these substances and examine their possible synergistic impacts on animal physiology and phenotype. We capitalized on a model avian system (the house finch, Haemorhous mexicanus), where extensive information is available on the fitness roles of carotenoids, to test how variation in carotenoid and/or vitamin E concentrations in the diet impacts body accumulation of these compounds, factors related to oxidative damage (e.g., breast muscle and plasma oxidative-stress susceptibility, plasma nitric-oxide levels), and plumage color development. As in a previous study of ours on carotenoids and health in finches, we employed a 2×2 factorial experimental design on birds in both molting and non-molting conditions, to understand how seasonal shifts in carotenoid use (i.e., pigment incorporation into plumage) might alter the accumulation and roles of carotenoids and vitamins. As expected, lutein supplementation increased the level of circulating carotenoids in both experiments and the color of newly molted plumage. By contrast, vitamin E provisioning did not significantly affect plasma carotenoid levels or plumage coloration in either experiment. Interestingly, carotenoid provisioning decreased circulating vitamin E levels during molt, which suggests either molecular competition between carotenoids and tocopherol at the absorption/transport stages or that vitamin E serves as an antioxidant to offset harmful actions that carotenoids may have at very high concentrations. Finally, in both experiments, we found a reduction in breast-muscle oxidative damage for tocopherol-supplemented birds, which constitutes the first demonstration of a protective effect of vitamin E against oxidative stress in wild birds. Taken together, these findings provide an interesting contrast with our earlier work on season-specific physiological benefits of carotenoids in finches and point to complex associations between indicators of antioxidant and oxidative state in wild-caught animals.


Assuntos
Antioxidantes/administração & dosagem , Carotenoides/administração & dosagem , Suplementos Nutricionais , Tentilhões/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Tocoferóis/administração & dosagem , Animais , Carotenoides/farmacocinética , Plumas/efeitos dos fármacos , Plumas/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Óxido Nítrico/sangue , Tocoferóis/farmacocinética
16.
Curr Drug Targets ; 14(13): 1533-41, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23859472

RESUMO

Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/ß-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osteoporose/tratamento farmacológico , Tocotrienóis/farmacologia , Animais , Conservadores da Densidade Óssea/química , Remodelação Óssea/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Osteogênese/efeitos dos fármacos , Osteoporose/genética , Osteoporose/metabolismo , Tocoferóis/farmacocinética , Tocotrienóis/química , Via de Sinalização Wnt/efeitos dos fármacos
17.
Nutr Cancer ; 65(6): 919-29, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22098224

RESUMO

Studies suggest that tomato and soy foods may contribute to a lower risk of certain cancers. We developed a novel soy germ tomato juice to be used in controlled cancer prevention trials. This study describes an initial test of compliance, phytochemical bioavailability, and effects on biomarkers of blood lipids. Healthy men and women (n = 18) consumed a soy germ-fortified juice daily (300 mL supplying 66 mg isoflavones and 22 mg lycopene) for 8 wk. A single-dose bioavailability study was completed on day 1 and isoflavones in plasma and urine, and lycopene in the plasma, were measured. All subjects completed the trial, with 97.7% ± 3.5% (mean ± SD) of the scheduled juice consumed. No adverse effects were documented. The postprandial study indicated that 3.1% ± 2.3% of lycopene was absorbed and that 49.3% ± 12.1% isoflavones ingested were recovered in 24-h urines. Lycopene plasma concentration changed from 0.60 ± 0.22 to 1.24 ± 0.30 µmol/L during 8 wk of consumption. Juice consumption significantly improved resistance of LDL+VLDL-C to Cu(2+)-mediated oxidation (P = 0.039), HDL-C (47.3 ± 15.8 to 51.7 ± 14.8 mg/dL, P < 0.001), and the ratio of total-C/HDL-C (4.25 ± 1.59 to 3.63 ± 1.16, P < 0.001) at 8 wk. A well-characterized soy-fortified tomato juice can be produced in large scale for multiinstitutional long-term cancer prevention trials and showed excellent compliance with no toxicity, while demonstrating absorption of biologically active phytochemicals.


Assuntos
Anticarcinógenos/farmacocinética , Bebidas , Carotenoides/farmacocinética , Alimentos Fortificados , Neoplasias/prevenção & controle , Alimentos de Soja , Adulto , Anticarcinógenos/administração & dosagem , Disponibilidade Biológica , Índice de Massa Corporal , Carotenoides/administração & dosagem , Carotenoides/sangue , HDL-Colesterol/sangue , LDL-Colesterol , Feminino , Humanos , Isoflavonas/administração & dosagem , Isoflavonas/sangue , Isoflavonas/farmacocinética , Licopeno , Solanum lycopersicum/química , Masculino , Cooperação do Paciente , Inquéritos e Questionários , Tocoferóis/administração & dosagem , Tocoferóis/sangue , Tocoferóis/farmacocinética , Triglicerídeos/sangue , Adulto Jovem
18.
Nutrition ; 29(1): 338-44, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23237656

RESUMO

OBJECTIVE: The bioaccessibility of bioactives from pistachios has not been previously evaluated. In the present study we quantified the release of polyphenols, xanthophylls (lutein), and tocopherols from pistachios (raw pistachios, roasted salted pistachios, and muffins made with raw pistachios) during simulated human digestion. METHODS: A dynamic gastric model of digestion that provides a realistic and predictive simulation of the physical and chemical processing and accurately mimics the residence time and the luminal environment within the human stomach was used for the digestion studies. RESULTS: More than 90% of the polyphenols were released in the gastric compartment, with virtually total release in the duodenal phase. No significant differences were observed between raw shelled and roasted salted pistachio. The presence of a food matrix (muffin) decreased the bioaccessibility of protocatechuic acid (78%) and luteolin (36%). Almost 100% bioaccessibility of lutein and tocopherols was found after duodenal digestion, with no difference among the three samples. CONCLUSION: The rapid release of the assayed bioactives in the stomach maximizes the potential for absorption in the duodenum and contributes to the beneficial relation between pistachio consumption and health-related outcomes.


Assuntos
Digestão/fisiologia , Pistacia , Polifenóis/farmacocinética , Tocoferóis/farmacocinética , Xantofilas/farmacocinética , Disponibilidade Biológica , Carotenoides/química , Carotenoides/farmacocinética , Manipulação de Alimentos , Mucosa Gástrica/metabolismo , Humanos , Absorção Intestinal/fisiologia , Luteína/química , Luteína/farmacocinética , Modelos Biológicos , Pistacia/química , Polifenóis/química , Tocoferóis/química , Xantofilas/química
19.
J Agric Food Chem ; 60(29): 7282-90, 2012 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-22738607

RESUMO

A study was made of the effect of high-pressure processing (HPP) and thermal treatment (TT) on plant bioactive compounds (tocopherols, carotenoids, and ascorbic acid) in 12 fruit juice-milk beverages and of how the food matrix [whole milk (JW), skimmed milk (JS), and soy milk (JSy)] modulates their bioaccessibility (%). HPP (400 MPa/40 °C/5 min) produced a significant decrease in carotenoid and ascorbic acid bioaccessibility in all three beverages and maintained the bioaccessibility of tocopherols in JW and JS while decreasing it in JSy. TT (90 °C/30 s) produced a significant decrease in tocopherol and carotenoid bioaccessibility in all three beverages and increased the bioaccessibility of ascorbic acid. With regard to the food matrix, α-tocopherol and ascorbic acid bioaccessibility was greatest in JW beverages and lowest in JSy beverages, whereas no significant differences were found among the three beverages in terms of carotenoid bioaccessibility. HPP-treated samples showed higher tocopherol and carotenoid bioaccessibility than TT-treated samples, thus indicating that HPP combined with a milk matrix positively modulates the bioaccessibility of certain types of bioactive components of food, mainly those of a lipophilic nature.


Assuntos
Ácido Ascórbico/farmacocinética , Carotenoides/farmacocinética , Manipulação de Alimentos/métodos , Leite/química , Alimentos de Soja/análise , Tocoferóis/farmacocinética , Animais , Ácido Ascórbico/análise , Bebidas/análise , Disponibilidade Biológica , Carotenoides/análise , Frutas/química , Temperatura Alta , Técnicas In Vitro , Pressão , Tocoferóis/análise
20.
J Nutr ; 142(3): 513-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22298568

RESUMO

The natural vitamin E family is composed of 8 members equally divided into 2 classes: tocopherols (TCP) and tocotrienols (TE). A growing body of evidence suggests TE possess potent biological activity not shared by TCP. The primary objective of this work was to determine the concentrations of TE (200 mg mixed TE, b.i.d.) and TCP [200 mg α-TCP, b.i.d.)] in vital tissues and organs of adults receiving oral supplementation. Eighty participants were studied. Skin and blood vitamin E concentrations were determined from healthy participants following 12 wk of oral supplementation of TE or TCP. Vital organ vitamin E levels were determined by HPLC in adipose, brain, cardiac muscle, and liver of surgical patients following oral TE or TCP supplementation (mean duration, 20 wk; range, 1-96 wk). Oral supplementation of TE significantly increased the TE tissue concentrations in blood, skin, adipose, brain, cardiac muscle, and liver over time. α-TE was delivered to human brain at a concentration reported to be neuroprotective in experimental models of stroke. In prospective liver transplantation patients, oral TE lowered the model for end-stage liver disease (MELD) score in 50% of patients supplemented, whereas only 20% of TCP-supplemented patients demonstrated a reduction in MELD score. This work provides, to our knowledge, the first evidence demonstrating that orally supplemented TE are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of TE against stroke and end-stage liver disease in humans.


Assuntos
Doença Hepática Terminal/dietoterapia , Tocotrienóis/administração & dosagem , Tocotrienóis/farmacocinética , Adulto , Transporte Biológico Ativo , Suplementos Nutricionais , Progressão da Doença , Doença Hepática Terminal/metabolismo , Doença Hepática Terminal/prevenção & controle , Feminino , Humanos , Transplante de Fígado , Masculino , Estudos Prospectivos , Distribuição Tecidual , Tocoferóis/administração & dosagem , Tocoferóis/farmacocinética , Vitamina E/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...