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1.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361696

RESUMO

The nutritional composition and productivity of halophytes is strongly related to the biotic/abiotic stress to which these extremophile salt tolerant plants are subjected during their cultivation cycle. In this study, two commercial halophyte species (Inula crithmoides and Mesembryanthemum nodiflorum) were cultivated at six levels of salinity using a soilless cultivation system. In this way, it was possible to understand the response mechanisms of these halophytes to salt stress. The relative productivity decreased from the salinities of 110 and 200 mmol L-1 upwards for I. crithmoides and M. nodiflorum, respectively. Nonetheless, the nutritional profile for human consumption remained balanced. In general, I. crithmoides vitamin (B1 and B6) contents were significantly higher than those of M. nodiflorum. For both species, ß-carotene and lutein were induced by salinity, possibly as a response to oxidative stress. Phenolic compounds were more abundant in plants cultivated at lower salinities, while the antioxidant activity increased as a response to salt stress. Sensory characteristics were evaluated by a panel of culinary chefs showing a preference for plants grown at the salt concentration of 350 mmol L-1. In summary, salinity stress was effective in boosting important nutritional components in these species, and the soilless system promotes the sustainable and safe production of halophyte plants for human consumption.


Assuntos
Inula/química , Inula/crescimento & desenvolvimento , Mesembryanthemum/química , Mesembryanthemum/crescimento & desenvolvimento , Valor Nutritivo , Salinidade , Plantas Tolerantes a Sal/química , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Antioxidantes/farmacologia , Dieta Vegetariana , Humanos , Luteína/análise , Minerais/análise , Estresse Oxidativo , Fenóis/análise , Extratos Vegetais/farmacologia , Piridoxina/análise , Estresse Salino , Taninos/análise , Tiamina/análise , beta Caroteno/análise
2.
J Food Sci ; 86(9): 4197-4208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34370293

RESUMO

Although ginkgo nuts are very nutritious and loaded with numerous bioactive compounds, the nuts contain significant levels of unwanted compounds (ginkolic acids) which are toxic to consumption. To reduce or eliminate these toxic compounds without impacting the nutritional value and the bioactivity of the final product, an appropriate processing technology is needed. Thus, the effect of preheating (90 and 120°C) prior to drying (freeze drying: FD, hot air drying: HAD, and HAD in tandem with FD: HAD-FD) was evaluated on ginkgolic acids, pyridoxine analogues, phenolic compounds, and antioxidant properties of ginkgo nuts. Our results pointed out a significant decrease (below 50%) of ginkgolic acids in ginkgo nuts samples processed at 90°C compared to the control. The major compounds found after treatments were respectively, kaempferol (36.66-354.38 µg/g), quercetin (9.04-183.71 µg/g), and caffeic acid (19.66-106.88 µg/g). Principal component analysis (PCA) revealed that preheating at 90°C prior to HAD-FD would be a proper and reasonable approach for preserving the bioactive compounds and antioxidant capacity of ginkgo nuts (EC50 ranged from 2.25 to 4.60 mg/mL) while significantly reducing their content in toxic compounds.


Assuntos
Antioxidantes , Manipulação de Alimentos , Ginkgo biloba , Nozes , Piridoxina , Antioxidantes/química , Manipulação de Alimentos/métodos , Manipulação de Alimentos/normas , Alimentos em Conserva , Temperatura Alta , Nozes/química , Extratos Vegetais/química , Folhas de Planta/química , Salicilatos/análise
3.
Toxicon ; 201: 66-73, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34425140

RESUMO

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba seeds and leaves. In this work, the body weights, histopathological changes, plasma vitamin B6 (VB6), biochemical parameters, oxidative stress responses, and amino acids of rats were investigated after intragastric administration of MPN for 15 days. Results showed that intragastric administration of 50 mg/kg BW MPN caused pathological changes in the brain and heart tissues of rats. Administration of 10 mg/kg and 30 mg/kg BW MPN can significantly increase VB6 analogs in the plasma of rats, such as pyridoxal-5'-phosphate, pyridoxal. Results of biochemical parameters indicated that MPN can damage brains and hearts by changing the enzyme activity of these organs. These results suggest that consumption of Ginkgo biloba seeds for the long term, even in a small quantity, may lead to poisoning.


Assuntos
Ginkgo biloba , Hematologia , Animais , Estresse Oxidativo , Extratos Vegetais/toxicidade , Piridoxina/análogos & derivados , Ratos , Sementes
4.
Seizure ; 91: 369-373, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34298455

RESUMO

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy that is responsive to pharmacologic doses of vitamin B6. The deficiency of antiquitin, an enzyme involved in the catabolism of lysine, is believed to be its key molecular basis. Research to date has tended to focus on two known catabolic pathways of lysine, namely, saccharopine and pipecolic acid. However, the occurrence of oxidative stress and the presence of its metabolites have been only briefly highlighted in the literature. Owing to the importance of the topic and its potential for future diagnosis, prognosis and therapy, this paper reviews the suggested mechanisms of oxidative stress in antiquitin deficiency along with the proposed reactions and intermediates, and finally, discusses the challenges and opportunities.


Assuntos
Epilepsia , Epilepsia/tratamento farmacológico , Humanos , Estresse Oxidativo , Piridoxina/uso terapêutico
5.
Mol Biol Rep ; 48(7): 5513-5518, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34302584

RESUMO

Pyridoxine (PN), one of the vitamers of vitamin B6, plays an important role in the maintenance of epidermal function and is used to treat acne and rough skin. Clinical studies have revealed that PN deficiency causes skin problems such as seborrheic dermatitis and stomatitis. However, the detailed effects of PN and its mechanism of action in epidermal function are poorly understood. In this study, we examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN specifically causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation. In addition, PN treatment caused an increase in the production of filaggrin protein in a concentration-dependent manner. Treatment with P2x purinoceptor antagonists, namely, pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate and TNP-ATP hydrate, induced an increase in the filaggrin protein levels. Moreover, we showed that elevated filaggrin production induced upon PN treatment was suppressed by ATP (known as P2x purinoceptor agonist). This study is the first to report that PN causes an increase in filaggrin transcription and production, and these results suggest that PN-induced filaggrin production may be a useful target as a daily care component in atopic dermatitis, wherein filaggrin levels are specifically reduced.


Assuntos
Proteínas de Filamentos Intermediários/genética , Queratinócitos/metabolismo , Piridoxina/metabolismo , Células Cultivadas , Epiderme/metabolismo , Regulação da Expressão Gênica , Humanos , Piridoxina/farmacologia
6.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147902

RESUMO

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Assuntos
Ácido Ascórbico/química , Ácido Ascórbico/uso terapêutico , Sulfato de Magnésio/química , Sulfato de Magnésio/uso terapêutico , Niacinamida/química , Niacinamida/uso terapêutico , Ácido Pantotênico/química , Ácido Pantotênico/uso terapêutico , Piridoxina/química , Piridoxina/uso terapêutico , Riboflavina/química , Riboflavina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Tiamina/química , Tiamina/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Cães , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Composição de Medicamentos , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Sulfato de Magnésio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Niacinamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ácido Pantotênico/farmacologia , Piridoxina/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Riboflavina/farmacologia , Sepse/patologia , Superóxido Dismutase/metabolismo , Tiamina/farmacologia
7.
Eur J Paediatr Neurol ; 33: 112-120, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34153871

RESUMO

BACKGROUND: Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort. METHODS: Neurological outcome was assessed in 24 patients (age 1-26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed. RESULTS: Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ > 85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients. DISCUSSION: Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed.


Assuntos
Cognição , Pessoas com Deficiência , Epilepsia , Transtornos Motores , Adolescente , Adulto , Aldeído Desidrogenase , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Piridoxina , Adulto Jovem
8.
Seizure ; 91: 75-80, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34118609

RESUMO

OBJECTIVE: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome. METHODS: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m2/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks. RESULTS: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms. CONCLUSIONS: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design.


Assuntos
Piridoxina , Espasmos Infantis , Administração Oral , Hormônio Adrenocorticotrópico/uso terapêutico , Quimioterapia Combinada , Humanos , Lactente , Piridoxina/uso terapêutico , Espasmos Infantis/tratamento farmacológico
9.
Sci Rep ; 11(1): 12668, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135415

RESUMO

Supplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5'-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously untreated advanced carcinoma of the digestive tract to assess the impact of high-dose pyridoxine (PN) on the antitumor activity of regimens comprising FUra and FA. Five patients had colorectal adenocarcinoma (CRC); 5 had pancreas adenocarcinoma (PC); and 3 had squamous cell carcinoma of the esophagus (EC). Patients with CRC and with PC received oxaliplatin, irinotecan, FUra and FA, and patients with EC had paclitaxel, carboplatin, FUra and FA. PN iv from 1000 to 3000 mg/day preceded each administration of FA and FUra. Eleven patients responded. Two patients with CRC attained CRs and 3 had PRs with reduction rates ≥ 78%. Two patients with PC attained CRs, and 2 had PRs with reduction rates ≥ 79%. Responders experienced disappearance of most metastases. Of 3 patients with EC, 2 attained CRs. Median time to attain a response was 3 months. Unexpected toxicity did not occur. Results suggest that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Combinação de Medicamentos , Feminino , Fluoruracila/uso terapêutico , Trato Gastrointestinal/patologia , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Piridoxina/uso terapêutico
10.
BMC Ophthalmol ; 21(1): 212, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985475

RESUMO

BACKGROUND: Ectopia lentis is the common ocular manifestation of homocystinuria resulting from cystathionine beta-synthase (CBS) deficiency which has a high risk of thromboembolic complications. CASE PRESENTATION: The present study reports the case of a teenager with recurrent lens dislocation and glaucoma. He was diagnosed with CBS deficiency according to a high level of serum homocysteine and compound heterozygous mutations at two different positions on the CBS gene. Antiglaucoma eyedrops and a mydriatic successfully controlled the intraocular pressure, while oral pyridoxine and betaine uptake lowered the serum homocysteine level effectively. CONCLUSIONS: Children with CBS deficiency may suffer from ectopia lentis, glaucoma and/or amblyopia. We firstly discovered a new mutation of CBS c. 697 T > G which had not been reported before. The patient was pyridoxine responsive and well controlled by medicine.


Assuntos
Ectopia do Cristalino , Homocistinúria , Adolescente , Criança , Cistationina beta-Sintase/genética , Homocistinúria/complicações , Homocistinúria/genética , Humanos , Masculino , Mutação , Piridoxina/uso terapêutico
11.
Am J Med Sci ; 361(6): 791-794, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958192

RESUMO

Pyridoxine is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters. Deficiency of pyridoxine results in impaired transcellular signaling between neurons and presents with muscular convulsions, hyperirritability, and peripheral neuropathy. Deficiency of pyridoxine is usually found in association with other vitamin B deficiencies such as folate (vitamin B9) and cobalamin (vitamin B12). Isolated pyridoxine deficiency is extremely rare. We present the case of a 59-year old female with type 2 diabetes who complained of painful muscle spasms. Her muscle spasms involved in both feet, which have spread proximally to her legs. She also experienced intermittent muscle spasms in her left arm, which is not alleviated by baclofen, cyclobenzaprine. Her plasma pyridoxal 5-phosphate confirmed pyridoxine deficiency. Vitamins B1, B3, B12, and folate were within normal limits. The patient received standard-dose intramuscular pyridoxine injections for three weeks followed by oral supplements for 3 months and her symptoms resolved. This case illustrates the rare instance of isolated pyridoxine deficiency in type 2 diabetes patient manifesting as myoclonic muscle spasms involving the legs and arms in the absence of objective polyneuropathy. Pyridoxine level should, therefore, be assessed in patients with type 2 diabetes, including newly diagnosed patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Piridoxina/sangue , Espasmo/sangue , Deficiência de Vitamina B 6/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Piridoxina/administração & dosagem , Piridoxina/deficiência , Espasmo/diagnóstico , Espasmo/tratamento farmacológico , Deficiência de Vitamina B 6/diagnóstico , Deficiência de Vitamina B 6/tratamento farmacológico
12.
Adv Nutr ; 12(5): 1911-1929, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33912895

RESUMO

Vitamin B-6 in the form of pyridoxine (PN) is commonly used by the general population. The use of PN-containing supplements has gained lots of attention over the past years as they have been related to the development of peripheral neuropathy. In light of this, the number of reported cases of adverse health effects due to the use of vitamin B-6 have increased. Despite a long history of study, the pathogenic mechanisms associated with PN toxicity remain elusive. Therefore, the present review is focused on investigating the mechanistic link between PN supplementation and sensory peripheral neuropathy. Excessive PN intake induces neuropathy through the preferential injury of sensory neurons. Recent reports on hereditary neuropathy due to pyridoxal kinase (PDXK) mutations may provide some insight into the mechanism, as genetic deficiencies in PDXK lead to the development of axonal sensory neuropathy. High circulating concentrations of PN may lead to a similar condition via the inhibition of PDXK. The mechanism behind PDXK-induced neuropathy is unknown; however, there is reason to believe that it may be related to γ-aminobutyric acid (GABA) neurotransmission. Compounds that inhibit PDXK lead to convulsions and reductions in GABA biosynthesis. The absence of central nervous system-related symptoms in PDXK deficiency could be due to differences in the regulation of PDXK, where PDXK activity is preserved in the brain but not in peripheral tissues. As PN is relatively impermeable to the blood-brain barrier, PDXK inhibition would similarly be confined to the peripheries and, as a result, GABA signaling may be perturbed within peripheral tissues, such as sensory neurons. Perturbed GABA signaling within sensory neurons may lead to excitotoxicity, neurodegeneration, and ultimately, the development of peripheral neuropathy. For several reasons, we conclude that PDXK inhibition and consequently disrupted GABA neurotransmission is the most plausible mechanism of toxicity.


Assuntos
Doenças do Sistema Nervoso Periférico , Piridoxina , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Piridoxal Quinase , Piridoxina/toxicidade , Vitamina B 6/toxicidade , Vitaminas
13.
Semergen ; 47(8): 551-562, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33865694

RESUMO

Low back pain, as well as other musculoskeletal disorders (neck pain, osteoarthritis, etc.), are a very frequent cause of consultation both in primary care and in other hospital specialties and are usually associated with high functional and work disability. Acute low back pain can present different nociceptive, neuropathic and nonciplastic components, which leads to consider it as a mixed type pain. The importance of the concept of mixed pain is due to the fact that the symptomatic relief of these pathologies requires a multimodal therapeutic approach to various pharmacological targets. The antinociceptive role of the B vitamin complex has been recognized for several decades, specifically the combination of Thiamine, Pyridoxine and Cyanocobalamin (TPC). Likewise, there is accumulated evidence that indicates an adjuvant analgesic action in low back pain. The aim of the present review is to present the existing evidence and the latest findings on the therapeutic effects of the TPC combination in low back pain. Likewise, some of the most relevant mechanisms of action involved that can explain these effects are analyzed. The reviewed evidence indicates that the combined use of PCT has an adjuvant analgesic effect in mixed pain, specifically in low back pain and other musculoskeletal disorders with nociceptive and neuropathic components. This effect can be explained by an anti-inflammatory, antinociceptive, neuroprotective and neuromodulatory action of the TPC combination on the descending pain system.


Assuntos
Complexo Vitamínico B , Dor nas Costas , Humanos , Piridoxina , Tiamina , Vitamina B 12
14.
Brain Dev ; 43(6): 680-687, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33824024

RESUMO

OBJECTIVE: We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs). METHODS: In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20-30 mg/kg/day) for 1 year, in addition to previous treatment. RESULTS: All nine enrolled patients (mean age: 66.3 ± 44.3 months) exhibited marked decreases in levels of CD16, a glycosylphosphatidylinositol-anchored protein, on blood granulocytes. The underlying genetic causes of IGDs were PIGO, PIGL, and unknown gene mutations in two, two, and five patients, respectively. Six patients experienced seizures, while all patients presented with developmental delay (mean developmental age: 11.1 ± 8.1 months). Seizure frequencies were markedly (>50%) and drastically (>90%) reduced in three and one patients who experienced seizures, respectively. None of the patients presented with seizure exacerbation. Eight of nine patients exhibited modest improvements in development (P = 0.14). No adverse events were observed except for mild transient diarrhea in one patient. CONCLUSION: One year of daily high-dose pyridoxine treatment was effective in the treatment of seizures in more than half of our patients with IGDs and modestly improved development in the majority of them. Moreover, such treatment was reasonably safe. These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm our findings. (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number: UMIN000024185.).


Assuntos
Glicosilfosfatidilinositóis/deficiência , Piridoxina/farmacologia , Convulsões/tratamento farmacológico , Complexo Vitamínico B/farmacologia , Adolescente , Criança , Pré-Escolar , Feminino , Glicosilfosfatidilinositóis/genética , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Estudos Prospectivos , Piridoxina/administração & dosagem , Convulsões/complicações , Convulsões/etiologia , Convulsões/genética , Complexo Vitamínico B/administração & dosagem
16.
Artigo em Inglês | MEDLINE | ID: mdl-33773258

RESUMO

Water-soluble vitamins are essential dietary components with a multitude of important functions that require quantification from food sources to characterise the nutritional status of food. In this study, we have developed a hydrophilic interaction chromatography (HILIC) based method coupled to single-quadrupole mass spectrometry (MS) for the analysis of selected water-soluble vitamins. Due to their involvement in energy release from macronutrients, the quantification of thiamine (B1), riboflavin (B2), nicotinamide (B3) and pyridoxine (B6) offers significant value in food analysis. A commercially available vegetable soup was selected as the food matrix for this study and utilised to develop an efficient extraction procedure for the vitamins of interest. Vitamins were extracted using meta-phosphoric acid coupled with a reducing agent, DL-dithiothreitol (DTT) to produce the parent compound. The extracted vitamins were then analysed using an LC-MS system with electrospray - atmospheric pressure ionization (ES-API) source, operated in positive single ion monitoring (SIM) mode. The MS provided good linearity within the investigated range from 5 to 400 ng/mL with coefficient of determination (r2) ranging from 0.98 to 0.99. Retention times (0.65-9.04 min) were reproducible and no coelution between vitamins was observed. Limit of detection (LOD) varied from 2.4 to 9.0 ng/mL and limit of quantification (LOQ) was from 8 to 30 ng/mL, comparable to previously published studies. The extraction method provided good intra-day (%CV 1.56-6.56) and inter-day precision (%CV 8.07-10.97). Standard injections were used as part of quality control measures and provided excellent reproducibility (%CV 0.9-3.4). The overall runtime of this method was 19 min, including column reconditioning. Using this method, the quantity of thiamine (67 ±â€¯7 ng/g), riboflavin (423 ±â€¯39 ng/g), nicotinamide (856 ±â€¯77 ng/g) and pyridoxine (133 ±â€¯11 ng/g) was determined from a complex food matrix. In conclusion, we have developed a rapid and reliable, HILIC-single quad MS method utilising SIM for the low-level quantification of four B vitamins in a vegetable soup matrix in under 20 min. This method has shown excellent linearity, intra- and inter-day reproducibility and is directly applicable to other plant-based food matrices.


Assuntos
Cromatografia Líquida/métodos , Análise de Alimentos/métodos , Espectrometria de Massas/métodos , Vitaminas/análise , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Modelos Lineares , Niacinamida/análise , Piridoxina/análise , Reprodutibilidade dos Testes , Riboflavina/análise , Solubilidade , Tiamina/análise
17.
EcoSal Plus ; 9(2)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33787481

RESUMO

Vitamin B6 is an ensemble of six interconvertible vitamers: pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL), and their 5'-phosphate derivatives, PNP, PMP, and PLP. Pyridoxal 5'-phosphate is a coenzyme in a variety of enzyme reactions concerning transformations of amino and amino acid compounds. This review summarizes all known and putative PLP-binding proteins found in the Escherichia coli MG1655 proteome. PLP can have toxic effects since it contains a very reactive aldehyde group at its 4' position that easily forms aldimines with primary and secondary amines and reacts with thiols. Most PLP is bound either to the enzymes that use it as a cofactor or to PLP carrier proteins, protected from the cellular environment but at the same time readily transferable to PLP-dependent apoenzymes. E. coli and its relatives synthesize PLP through the seven-step deoxyxylulose-5-phosphate (DXP)-dependent pathway. Other bacteria synthesize PLP in a single step, through a so-called DXP-independent pathway. Although the DXP-dependent pathway was the first to be revealed, the discovery of the widespread DXP-independent pathway determined a decline of interest in E. coli vitamin B6 metabolism. In E. coli, as in most organisms, PLP can also be obtained from PL, PN, and PM, imported from the environment or recycled from protein turnover, via a salvage pathway. Our review deals with all aspects of vitamin B6 metabolism in E. coli, from transcriptional to posttranslational regulation. A critical interpretation of results is presented, in particular, concerning the most obscure aspects of PLP homeostasis and delivery to PLP-dependent enzymes.


Assuntos
Piridoxina , Vitamina B 6 , Escherichia coli/genética , Fosfato de Piridoxal , Vitaminas
18.
Appl Microbiol Biotechnol ; 105(6): 2297-2305, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33665688

RESUMO

The term vitamin B6 is a designation for the vitamers pyridoxal, pyridoxamine, pyridoxine and the respective phosphate esters pyridoxal-5'-phosphate (PLP), pyridoxamine-5'-phosphate and pyridoxine-5'-phosphate. Animals and humans are unable to synthesise vitamin B6. These organisms have to take up vitamin B6 with their diet. Therefore, vitamin B6 is of commercial interest as a food additive and for applications in the pharmaceutical industry. As yet, two naturally occurring routes for de novo synthesis of PLP are known. Both routes have been genetically engineered to obtain bacteria overproducing vitamin B6. Still, major genetic engineering efforts using the existing pathways are required for developing fermentation processes that could outcompete the chemical synthesis of vitamin B6. Recent suppressor screens using mutants of the Gram-negative and Gram-positive model bacteria Escherichia coli and Bacillus subtilis, respectively, carrying mutations in the native pathways or heterologous genes uncovered novel routes for PLP biosynthesis. These pathways consist of promiscuous enzymes and enzymes that are already involved in vitamin B6 biosynthesis. Thus, E. coli and B. subtilis contain multiple promiscuous enzymes causing a so-called underground metabolism allowing the bacteria to bypass disrupted vitamin B6 biosynthetic pathways. The suppressor screens also show the genomic plasticity of the bacteria to suppress a genetic lesion. We discuss the potential of the serendipitous pathways to serve as a starting point for the development of bacteria overproducing vitamin B6. KEY POINTS: • Known vitamin B6 routes have been genetically engineered. • Underground metabolism facilitates the emergence of novel vitamin B6 biosynthetic pathways. • These pathways may be suitable to engineer bacteria overproducing vitamin B6.


Assuntos
Escherichia coli , Fosfato de Piridoxal , Animais , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Vias Biossintéticas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Fosfato de Piridoxal/metabolismo , Piridoxina , Vitamina B 6
19.
Toxins (Basel) ; 13(2)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530619

RESUMO

Ginkgo biloba seeds are wildly used in the food and medicine industry. It has been found that 4'-O-methylpyridoxine (MPN) is responsible for the poisoning caused by G. biloba seeds. The objective of this study was to explore and optimize the extraction method of MPN from G. biloba seeds, and investigate its toxic effect on human gastric epithelial cells (GES-1) and the potential related mechanisms. The results showed that the extraction amount of MPN was 1.933 µg/mg, when extracted at 40 °C for 100 min, with the solid-liquid ratio at 1:10. MPN inhibited the proliferation of GES-1 cells, for which the inhibition rate was 38.27% when the concentration of MPN was 100 µM, and the IC50 value was 127.80 µM; meanwhile, the cell cycle was arrested in G2 phase. High concentration of MPN (100 µM) had significant effects on the nucleus of GES-1 cells, and the proportion of apoptotic cells reached 43.80%. Furthermore, the Western blotting analysis showed that MPN could reduce mitochondrial membrane potential by increasing the expression levels of apoptotic proteins Caspase 8 and Bax in GES-1 cells. In conclusion, MPN may induce apoptosis in GES-1 cells, which leads to toxicity in the human body.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Ginkgo biloba , Extratos Vegetais/toxicidade , Piridoxina/análogos & derivados , Sementes , Caspase 8/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ginkgo biloba/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Piridoxina/isolamento & purificação , Piridoxina/toxicidade , Sementes/química , Proteína X Associada a bcl-2/metabolismo
20.
Poult Sci ; 100(4): 101008, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610900

RESUMO

Three isotopic tracers ([2,3,3-2H3]-L-serine, [2H11]-L-betaine, and [1-13C]-L-methionine) were administered by amnion injection into 18-day-old chick embryos to investigate the kinetics of methionine metabolism. The embryos utilized were from eggs collected from 34-week-old Cobb 500 broiler breeders that were fed either a control diet containing folic acid (1.25 mg/kg diet) and pyridoxine HCl (5 mg/kg diet) or diets devoid of supplemental pyridoxine or folic acid. Intermediate metabolites of methionine metabolism and polyamines were analyzed in 18-day-old chick embryos. There were no differences in hepatic [2H2] methionine or [2H3] cysteine enrichments or in physiological concentrations of sulfur amino acids for chick embryos from breeders fed the control diet and embryos from breeders fed diets containing no pyridoxine or folic acid. Supplementation of B6 or folic acid did not affect the production of methionine and cysteine in chick embryos. However, breeders fed the control diet with both folic acid and pyridoxine supplementation produced embryos with a two-fold reduction of hepatic homocysteine and increased spermine compared with embryos from breeders fed diets containing no supplemental pyridoxine or folic acid (P < 0.05). Hepatic S-adenosylmethionine for embryos from breeders fed no supplemental B6 was half the concentration compared with embryos from breeders fed the control diet. Embryos from breeders fed the control diet were utilized to determine the proportion of homocysteine going through remethylation and transsulfuration and also to determine the pathway of remethylation. Sixty-five percent of the methyl groups used for homocysteine remethylation from control embryos was via the MFMT pathway. Alternatively, 61% of homocysteine from control embryos was remethylated via the MFMT and the BHMT reactions and 39% of homocysteine was catabolized to cysteine via the transsulfuration pathway. These data show that in embryos, intermediate metabolites of methionine and polyamines increase in concentration when pyridoxine levels are provided in deficient concentrations to the breeder hen. In addition, this research demonstrates that folic acid deficient embryos conserve methionine, rather than catabolize it to cysteine.


Assuntos
Ácido Fólico , Vitamina B 6 , Animais , Embrião de Galinha , Galinhas , Dieta/veterinária , Feminino , Metionina , Óvulo , Piridoxina , Vitaminas
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