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1.
Bratisl Lek Listy ; 121(3): 235-241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115983

RESUMO

AIM: Hyperglycemia, oxidative stress and hyperlipidemia are features of diabetes mellitus. Thiamine has beneficial effects on carbohydrate metabolism and it was proposed that this vitamin has antihyperlipidemic and antioxidant effects. Our aim was to investigate the effects of thiamine on oxidative stress and metabolic changes in streptozotocin (STZ) induced diabetic rats. METHOD: Diabetes was induced by a single intraperitoneal injection of STZ. Thiamine (6 mg/kg) was added to drinking water for five weeks. The rats were divided into four groups: control rats; thiamine treated control rats; diabetic rats; thiamine treated diabetic rats. Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase (PON) and arylesterase (AE) activities were measured with spectrophotometric methods, and erythrocyte superoxide dismutase (SOD) and blood glutathione peroxidase (GSH-Px) activities were determined using commercial kits. RESULTS: Thiamine treatment reduced plasma and tissue MDA levels, serum glucose, total cholesterol and triglyceride levels, and increased serum high density lipoprotein- cholesterol and insulin levels, serum PON and AE, erythrocyte SOD and blood GSH-Px activities. CONCLUSION: Thiamine significantly improves oxidative stress and has hyperinsulinemic and antihyperlipidemic effects so we suggest that thiamine might be used as a supportive therapeutic agent in diabetes (Tab. 2, Fig. 3, Ref. 53).


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Estresse Oxidativo , Tiamina , Animais , Antioxidantes/farmacologia , Glicemia , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase , Tiamina/farmacologia
2.
Biochemistry (Mosc) ; 85(1): 27-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32079515

RESUMO

To study the mechanisms of the non-coenzyme action of thiamine and its diphosphate (ThDP) on brain proteins, proteins of acetone extract of bovine brain synaptosomes or the homogenate of rat brain cortex were subjected to affinity chromatography on thiamine-modified Sepharose. In the step-wise eluates by thiamine (at pH 7.4 or 5.6), NaCl, and urea, the occurrence of glutamate dehydrogenase (GDH) and isoenzymes of malate dehydrogenase (MDH) along with the influence of thiamine and/or ThDP on the enzymatic activities were characterized using mass spectrometry and kinetic experiments. Maximal activation of the malate dehydrogenase reaction by thiamine is observed after the protein elution with the acidic thiamine solution, which does not elute the MDH1 isoenzyme. Effects of exogenous thiamine or ThDP on the GDH activity may depend on endogenous enzyme regulators. For example, thiamine and/or ThDP activate the brain GDH in eluates from thiamine-Sepharose but inhibit the enzyme in the crude preparations applied to the sorbent. Inhibition of GDH by ThDP is observed using the ADP-activated enzyme. Compared to the affinity chromatography employing the elution by thiamine at pH 7.4, the procedure at pH 5.6 decreases the activation of GDH by thiamine (but not ThDP) in the eluates with NaCl and urea. Simultaneously, the MDH2 content and total GDH activity are higher after the affinity elution at pH 5.6 than at pH 7.4, suggesting the role of the known interaction of GDH with MDH2 in stabilizing the activity of GDH and in the regulation of GDH by thiamine. The biological potential of thiamine-dependent regulation of the brain GDH is confirmed in vivo by demonstration of changes in regulatory properties of GDH after administration of a high dose of thiamine to rats. Bioinformatics analysis of the thiamine-eluted brain proteins shows a specific enrichment of their annotation terms with "phosphoprotein", "acetylation", and "methylation". The relationship between thiamine and the posttranslational modifications in brain may contribute to the neuroprotective effects of high doses of thiamine, including the regulation of oxidation of the major excitatory neurotransmitter in brain - glutamate.


Assuntos
Encéfalo/enzimologia , Glutamato Desidrogenase/metabolismo , Malato Desidrogenase/metabolismo , Tiamina Pirofosfato/farmacologia , Tiamina/farmacologia , Animais , Bovinos , Ativação Enzimática , Oxirredução , Ratos , Ratos Wistar
3.
PLoS Biol ; 17(10): e3000512, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658248

RESUMO

Endocytosis of membrane proteins in yeast requires α-arrestin-mediated ubiquitylation by the ubiquitin ligase Rsp5. Yet, the diversity of α-arrestin targets studied is restricted to a small subset of plasma membrane (PM) proteins. Here, we performed quantitative proteomics to identify new targets of 12 α-arrestins and gained insight into the diversity of pathways affected by α-arrestins, including the cell wall integrity pathway and PM-endoplasmic reticulum contact sites. We found that Art2 is the main regulator of substrate- and stress-induced ubiquitylation and endocytosis of the thiamine (vitamin B1) transporters: Thi7, nicotinamide riboside transporter 1 (Nrt1), and Thi72. Genetic screening allowed for the isolation of transport-defective Thi7 mutants, which impaired thiamine-induced endocytosis. Coexpression of inactive mutants with wild-type Thi7 revealed that both transporter conformation and transport activity are important to induce endocytosis. Finally, we provide evidence that Art2 mediated Thi7 endocytosis is regulated by the target of rapamycin complex 1 (TORC1) and requires the Sit4 phosphatase but is not inhibited by the Npr1 kinase.


Assuntos
Arrestinas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Transporte de Nucleosídeos/genética , Processamento de Proteína Pós-Traducional , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Tiamina/metabolismo , Arrestinas/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Parede Celular/metabolismo , Endocitose/genética , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , Mutação , Proteínas de Transporte de Nucleosídeos/metabolismo , Ligação Proteica , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Estrutura Secundária de Proteína , Proteômica/métodos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais , Tiamina/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Complexos Ubiquitina-Proteína Ligase/genética , Complexos Ubiquitina-Proteína Ligase/metabolismo , Ubiquitinação
4.
Biochemistry (Mosc) ; 84(8): 829-850, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31522667

RESUMO

Thiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated protein rapsyn, and thiamine interaction with the TAS2R1 receptor, resulting in the activation of synaptic ion currents. The non-coenzyme regulatory binding of thiamine compounds has been demonstrated for the transcriptional regulator p53, poly(ADP-ribose) polymerase, prion protein PRNP, and a number of key metabolic enzymes that do not use ThDP as a coenzyme. The accumulated data indicate that the molecular mechanisms of the neurotropic action of thiamine are far broader than it has been originally believed, and closely linked to the metabolism of thiamine and its derivatives in animals. The significance of this topic has been illustrated by the recently established competition between thiamine and the antidiabetic drug metformin for common transporters, which can be the reason for the thiamine deficiency underlying metformin side effects. Here, we also discuss the medical implications of the research on thiamine, including the role of thiaminases in thiamine reutilization and biosynthesis of thiamine antagonists; molecular mechanisms of action of natural and synthetic thiamine antagonists, and biotransformation of pharmacological forms of thiamine. Given the wide medical application of thiamine and its synthetic forms, these aspects are of high importance for medicine and pharmacology, including the therapy of neurodegenerative diseases.


Assuntos
Hipoglicemiantes/metabolismo , Metformina/metabolismo , Tiamina/análogos & derivados , Tiamina/metabolismo , Complexo Vitamínico B/metabolismo , Animais , Encéfalo/metabolismo , Coenzimas , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Metformina/administração & dosagem , Metformina/efeitos adversos , Camundongos , Fosforilação , Transporte Proteico/fisiologia , Ratos , Tiamina/efeitos adversos , Tiamina/farmacologia , Deficiência de Tiamina/etiologia , Deficiência de Tiamina/prevenção & controle , Tiamina Pirofosfato/metabolismo , Complexo Vitamínico B/efeitos adversos , Complexo Vitamínico B/farmacologia
5.
Chem Biol Interact ; 311: 108795, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31419397

RESUMO

Citreoviridin (CIT), a mycotoxin and ATP synthase inhibitor, is regarded as one of aetiology factors of cardiac beriberi and Keshan disease. Thiamine (VB1) and selenium (Se) improve the recovery of these two diseases respectively. The underlying mechanisms of cardiotoxic effect of CIT and cardioprotective effect of VB1 and Se have not been fully elucidated. In this study, we found that ectopic ATP synthase was more sensitive to CIT treatment than mitochondrial ATP synthase in H9c2 cardiomyocytes. CIT inhibited the transcriptional activity of peroxisome proliferator activated receptor gamma (PPAR-γ) in mice hearts and H9c2 cells. PPAR-γ agonist attenuated the inhibitory effect of CIT on mechanistic target of rapamycin complex 2 (mTORC2) and stimulatory effect of CIT on autophagy in cardiomyocytes. CIT induced apoptosis through lysosomal-mitochondrial axis in cardiomyocytes. PPAR-γ agonist and autophagy inhibitor alleviated CIT-induced apoptosis and accelerated cardiac biomarker. VB1 and Se accelerated the basal transcriptional activity of PPAR-γ in mice hearts and H9c2 cells. Furthermore, VB1 and Se reversed the effect of CIT on PPAR-γ, autophagy and apoptosis. Our findings defined PPAR-γ-mTORC2-autophagy pathway as the key link between CIT cardiotoxicity and cardioprotective effect of VB1 and Se. The present study would shed new light on the pathogenesis of cardiomyopathy and the cardioprotective mechanism of micronutrients.


Assuntos
Apoptose/efeitos dos fármacos , Aurovertinas/farmacologia , Autofagia/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Tiamina/farmacologia , Animais , Aquaporinas/genética , Aquaporinas/metabolismo , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Masculino , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/metabolismo , Miocárdio/patologia , PPAR gama/agonistas , PPAR gama/genética , PPAR gama/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
6.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1629-1635, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259440

RESUMO

Thiamine is recognized as a cofactor for many enzymes involved in intermediary metabolism responsible for energy production. Animal model of thiamine deficiency (TD) included direct evaluation of glucose uptake by estimation of 3 H-deoxyglucose transport across red blood cells membranes and ß-oxidation of fatty acids in isolated leucocytes. Feeding of animals with the thiamine-deficient diet (0.018 mg/kg diet) for 30 days resulted in disturbances in energy production. The thiamine intake was limited not only by vitamin B1 deficiency in the diet, but also by time-dependent drop of feed consumption by rats fed this diet. At the end of experiment, diet consumption in this group of rats was 52% lower than in the control group. This was accompanied by low glucose uptake by erythrocytes of rats suffering vitamin B1 deficiency for longer time. At the end of experimental period, glucose uptake was over 2 times lower in TD erythrocytes than in control RBC. Such drop of energy production was not compensated by delivery of energy from fatty acid degradation. In leucocytes from TD rats, the ß-oxidation was also suppressed. Observed significant decrease of serum insulin from 2.25 ± 0.25 ng/ml (day 0) to 1.94 ± 0.17 ng/ml (day 30) might have significant impact on observed energy production disorders. The results from this study indicate that the thiamine deficiency significantly reduces feed intake and causes modest abnormalities in glucose and fatty acid utilization.


Assuntos
Glucose/metabolismo , Tiamina/farmacologia , Animais , Transporte Biológico , Dieta , Masculino , Oxirredução , Distribuição Aleatória , Ratos , Ratos Wistar , Deficiência de Tiamina
7.
Mayo Clin Proc ; 94(6): 1065-1072, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171116

RESUMO

Wernicke encephalopathy (WE) was first described by Carl Wernicke in 1881. WE is caused by thiamine deficiency. Alcoholism is the most common etiologic factor associated with WE in the United States, but it can occur in any patient with a nutritional deficiency state such as hyperemesis gravidarum, intestinal obstruction, and malignancy. WE is a clinical diagnosis. The common findings include mental status changes, ocular dysfunction, and a gait apraxia, present in only 10% of cases. Only a few cases of WE are diagnosed before death. Approximately 80% of patients with untreated WE have development of Korsakoff syndrome, which is characterized by memory impairment associated with confabulation. The initial clinical diagnosis of WE is critical, keeping in mind that the classic triad of symptoms is often absent. Recognition of nutritional deficiency and any portion of the classic triad should prompt treatment. Additionally, hypothermia, hypotension, and coma should raise clinical suspicion for the disease. Primary treatment includes timely administration of thiamine, for which the route and dosage remain controversial. Clinical judgment should be exercised in diagnosis and treatment (dosage, frequency, route of administration and duration) in all cases of WE. Overdiagnosis and overtreatment may be preferred to prevent prolonged or persistent neurocognitive impairments given the excellent safety profile of thiamine. Further prospective research is warranted to better understand the disease biology, risk factors, and treatment recommendations.


Assuntos
Tiamina/administração & dosagem , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico , Apraxia da Marcha , Humanos , Hipotensão , Transtornos da Memória , Tiamina/farmacologia , Encefalopatia de Wernicke/fisiopatologia
8.
BMJ Case Rep ; 12(6)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31243025

RESUMO

A female child with deafness was diagnosed to have neonatal diabetes mellitus at the age of 6 months, on routine evaluation prior to cochlear implant surgery. She presented to us at 11 months of age with diabetic ketoacidosis due to an intercurrent febrile illness. Her haematological parameters showed megaloblastic anaemia and thrombocytopenia. Therefore a possibility of Thiamine Responsive Megaloblastic Anaemia (TRMA) syndrome was considered. She was empirically treated with parenteral thiamine hydrochloride (Hcl). Subsequently, due to the unavailability of pharmacological preparation of oral thiamine Hcl in a recommended dose she was treated with benfotiamine. She had a sustained improvement in all her haematological parameters on oral benfotiamine. The insulin requirement progressively reduced and she is currently in remission for last 2 years. The genetic analysis confirmed the diagnosis of TRMA syndrome. Thus benfotiamine can be considered a new treatment option in management of TRMA syndrome.


Assuntos
Anemia Megaloblástica/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Perda Auditiva Neurossensorial/tratamento farmacológico , Deficiência de Tiamina/congênito , Tiamina/análogos & derivados , Administração Oral , Anemia Megaloblástica/complicações , Anemia Megaloblástica/diagnóstico , Diabetes Mellitus/diagnóstico , Cetoacidose Diabética/etiologia , Feminino , Mutação da Fase de Leitura , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/efeitos dos fármacos , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Tiamina/administração & dosagem , Tiamina/farmacologia , Deficiência de Tiamina/complicações , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/tratamento farmacológico , Resultado do Tratamento
9.
Food Environ Virol ; 11(3): 205-213, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30903597

RESUMO

This study investigated the synergistic effects of combined chlorine (200, 500, 700, and 1000 ppm) and vitamin B1 (1000, 2000, and 3000 ppm) on the murine norovirus-1 (MNV-1), a human norovirus (NoV) surrogate, on oyster surface. Vitamin B1 slightly reduced MNV-1 (0.04-0.3 log-reduction), whereas chlorine significantly reduced MNV-1 (0.4-1.0 log-reduction). The combined chlorine and vitamin B1 resulted in a 0.52-1.97 log-reduction of MNV-1. The synergistic reduction in the MNV titer was not dependent on the concentrations of chlorine and vitamin B1, and it ranged between 0.08 and 1.03 log10 PFU/mL. The largest synergistic reduction observed was for the combined 700 ppm chlorine and 1000 ppm vitamin B1. The pH and mechanical texture of the oysters were not significantly changed by the combined 0-1000 ppm chlorine and 3000 ppm vitamin B1. The overall sensory acceptability were significantly (P < 0.05) reduced in oysters treated with 1000 ppm chlorine and 3000 ppm vitamin B1 than in those treated with 0-700 ppm chlorine and 3000 ppm vitamin B1. This study suggests that the combined 700 ppm chlorine and 3000 ppm vitamin B1 could potentially be used to reduce NoV on oyster surface without causing concomitant changes in the mechanical texture, pH, or sensory qualities of the oysters.


Assuntos
Cloro/farmacologia , Crassostrea/virologia , Desinfetantes/farmacologia , Contaminação de Alimentos/prevenção & controle , Conservação de Alimentos/métodos , Norovirus/efeitos dos fármacos , Frutos do Mar/virologia , Tiamina/farmacologia , Animais , Sinergismo Farmacológico , Humanos , Norovirus/genética , Norovirus/crescimento & desenvolvimento , Paladar
10.
Cell Mol Biol (Noisy-le-grand) ; 65(1): 73-77, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30782298

RESUMO

Thiamine diphosphate (ThDP) is an essential cofactor for important enzymes in carbohydrate, amino acid and lipid metabolisms. It is also known that thiamine plays an important role in stress response of some organisms. In this study, we focused on the effect of thiamine on stress responses triggered by various stress agents. For this purpose, firstly, viability of Schizosaccharomyces pombe cell cultures was examined under oxidative, osmotic and heat stresses. The highest tolerance observed in cell viability due to the presence of extracellular thiamine (1.5 µM) was found only against oxidative stress. Then, enzyme activity of catalase and superoxide dismutase (SOD) involved in antioxidant defense mechanism and the expression analysis of genes encoding enzymes related to glucose metabolism and stress response pathways were investigated under oxidative stress. In this condition, it was not observed any difference in SOD and catalase activities, and their gene expressions due to the presence of thiamine, whereas the upregulation of pyruvate dehydrogenase (pdb1), transketolase (SPBC2G5.05), fructose-1,6-bis-phosphatase (fbp1) and the downregulation of pyruvate decarboxylase (pdc201) were observed. In conclusion, these findings suggest that extracellular thiamine leading to oxidative stress resistance have an impact on the regulation of glucose metabolism by shifting the energy generation from fermentation to respiration.


Assuntos
Glucose/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Schizosaccharomyces/metabolismo , Tiamina/farmacologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Estresse Oxidativo/genética , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/genética , Superóxido Dismutase/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-30595211

RESUMO

Cultured human lymphocytes were treated with vitamins K1 and B1, potential anticancer agents, either alone or in combination with irinotecan, a semisynthetic analogue of camptothecin. The frequency of sister chromatid exchanges (SCEs) was measured as an indicator of genotoxicity and the proliferation rate index (PRI) and mitotic index (MI) was measured as indicators of cytostatic effect. Vitamin K1 alone did not induce SCEs at the concentrations tested and combined with irinotecan does not increase SCE rates induced by irinotecan alone. Vitamin B1 significantly increased SCEs and, in combination with irinotecan, increased rates further (p < 0.05). Vitamin K1 decreased PRI and MI in combination with irinotecan, there were further increases in MI. At a low concentration, vitamin B1 reduced the levels of SCE and increased PRI induced by irinotecan. The use of these vitamins in combination with antitumor agents might reduce clinical side effects of the antineoplastics.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Irinotecano/farmacologia , Linfócitos/efeitos dos fármacos , Índice Mitótico , Troca de Cromátide Irmã/efeitos dos fármacos , Tiamina/farmacologia , Vitamina K 1/farmacologia , Células Cultivadas , Combinação de Medicamentos , Humanos , Testes de Mutagenicidade/métodos
12.
BMC Vet Res ; 15(1): 7, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606162

RESUMO

BACKGROUND: Overfeeding of high-concentrate diet (HC) frequently leads to subacute ruminal acidosis (SARA) in modern dairy cows' production. Thiamine supplementation has been confirmed to attenuate HC induced SARA by increasing ruminal pH and ratio of acetate to propionate, and decreasing rumen lactate, biogenic amines and lipopolysaccharide (LPS). The effects of thiamine supplementation in HC on rumen bacteria and fungi profile had been detected in our previous studies, however, effects of thiamine supplementation in HC on rumen non-methanogen archaea is still unclear. The objective of the present study was therefore to investigate the effects of thiamine supplementation on ruminal archaea, especially non-methanogens in HC induced SARA cows. RESULTS: HC feeding significantly decreased dry matter intake, milk production, milk fat content, ruminal pH and the concentrations of thiamine and acetate in rumen fluid compared with control diet (CON) (P < 0.05), while the concentrations of propionate and ammonia-nitrogen (NH3-N) were significantly increased compared with CON (P < 0.05). These changes caused by HC were inversed by thiamine supplementation (P < 0.05). The taxonomy results showed that ruminal archaea ranged from 0.37 to 0.47% of the whole microbiota. Four characterized phyla, a number of Candidatus archaea and almost 660 species were identified in the present study. In which Euryarchaeota occupied the largest proportion of the whole archaea. Furthermore, thiamine supplementation treatment significantly increased the relative abundance of non-methanogens compared with CON and HC treatments. Thaumarchaeota was increased in HC compared with CON. Thiamine supplementation significantly increased Crenarchaeota, Nanoarchaeota and the Candidatus phyla, however decreased Thaumarchaeota compared with HC treatment. CONCLUSIONS: HC feeding significantly decreased ruminal pH and increased the content of NH3-N which led to N loss and the increase of the relative abundance of Thaumarchaeota. Thiamine supplementation increased ruminal pH, improved the activity of ammonia utilizing bacteria, and decreased Thaumarchaeota abundance to reduce the ruminal NH3 content and finally reduced N loss. Overall, these findings contributed to the understanding of thiamine's function in dairy cows and provided new strategies to improve dairy cows' health under high-concentrate feeding regime.


Assuntos
Archaea/efeitos dos fármacos , Dieta/veterinária , Suplementos Nutricionais , Rúmen/microbiologia , Tiamina/farmacologia , Ração Animal , Animais , Archaea/genética , Bovinos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Lactação/efeitos dos fármacos , Metagenômica , Rúmen/química , Tiamina/análise
14.
Int J Biol Macromol ; 124: 1186-1196, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30521923

RESUMO

To contribute towards effective exploitation and utilization of natural antioxidants, response surface methodology (RSM) was employed to optimize the medium composition for the production of exopolysaccharides from the medicinal mushroom Ganoderma lingzhi (GLEPS). An optimal medium for GLEPS production was gave through Plackett-Burman design, path of steepest ascent, and Box-Behnken design as follows: glucose (59.62 g/L), yeast extract (10.03 g/L), CaCO3 (0.2 g/L), thiamine (45.13 mg/L), KH2PO4 (1.0 g/L), peptone (1.5 g/L), Tween 80 (10.26 mL/L), ZnSO4 (0.3 g/L), mannitol (1.5 g/L), MgSO4 (0.5 g/L), and aspartate (8.86 g/L). The GLEPS yield obtained was 3.57 ±â€¯0.21 g/L-3.16-fold higher than that produced in basal medium alone. The resulting GLEPS rich in uronic acid, d-mannose, l-rhamnose, and d-glucose, was a heteropolysaccharide with high-molecular weights (475,000 kDa and 21.6 kDa, 87.97%). It was demonstrated that the GLEPS with higher carbohydrate and uronic acid contents exhibited strong in vitro antioxidant activities via radical scavenging, reductive capacity, and chelation of transition metal catalysis. These findings indicated that RSM is an efficient tool to predict the composition of culture medium required for maximizing GLEPS yield, and GLEPS had potent antioxidant activities and could be explored as a novel natural antioxidant in functional food or medicine.


Assuntos
Antioxidantes/química , Meios de Cultura/química , Polissacarídeos Fúngicos/química , Ganoderma/química , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Ácido Aspártico/química , Ácido Aspártico/farmacologia , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Meios de Cultura/farmacologia , Análise Fatorial , Polissacarídeos Fúngicos/biossíntese , Polissacarídeos Fúngicos/isolamento & purificação , Ganoderma/efeitos dos fármacos , Ganoderma/metabolismo , Glucose/química , Glucose/farmacologia , Radical Hidroxila/antagonistas & inibidores , Radical Hidroxila/química , Manitol/química , Manitol/farmacologia , Manose/química , Manose/farmacologia , Peptonas/química , Peptonas/farmacologia , Picratos/antagonistas & inibidores , Picratos/química , Polissorbatos/química , Polissorbatos/farmacologia , Ramnose/química , Ramnose/farmacologia , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química , Superóxidos/antagonistas & inibidores , Superóxidos/química , Tiamina/química , Tiamina/farmacologia
15.
J Photochem Photobiol B ; 189: 318-325, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30466067

RESUMO

BACKGROUND: Ultraviolet radiation (UVR) is known to be harmful to normal human epidermal keratinocytes (NHEKs) of the epidermal skin layer, as well as to hair-follicle-associated keratinocytes. An oral formulation containing l-cystine, thiamin, calcium d-pantothenate, medicinal yeast, keratin and p-aminobenzoic acid (Panto[vi]gar®) has demonstrated clinical efficacy for the treatment of diffuse telogen effluvium; however, its mode of action at the cellular level, and in particular whether protective mechanisms are involved, has yet to be elucidated. OBJECTIVES: To assess the capacity of ingredients of this oral formulation, both separately and in combination, to modulate the effects of UVR in growth-limited NHEKs in vitro. METHODS: NHEKs were incubated in keratinocyte basal medium, keratinocyte basal medium lacking cystine, thiamin, calcium d-pantothenate, folic acid and biotine (minimal growth medium [MGM]) or MGM plus test compound. Test compounds comprised the following four ingredients related to the oral formulation: l-cystine, thiamin, calcium d-pantothenate and folic acid (a proposed metabolite of p-aminobenzoic acid), and a combination of these (Panto[vi]gar®-in vitro correlate; P-IC). The effect of different doses of these compounds on the metabolic activity and proliferation of NHEKs was tested, as well as their influence on the impact of UV light on NHEKs assessed by monitoring metabolic activity, cell number and apoptosis induction. RESULTS: Compared with basal medium, MGM reduced the proliferation of NHEKs in a time-dependent manner. Reduced proliferation is a characteristic of the multifactorial and complex phenotype associated with diffuse hair loss. l-cystine (50 µM) increased metabolic activity and proliferation 3-fold versus MGM (p < 0.05). Thiamin also had a significant effect (p < 0.05) on proliferation and metabolic activity of NHEKs, but calcium d-pantothenate and folic acid did not when tested individually in this in vitro model. In the presence of P-IC, metabolic activity increased 4-fold and proliferation 3-fold compared with MGM alone (p < 0.05 for both). Following UV irradiation, cells in MGM showed a 72% reduction in metabolic activity, while P-IC-treated cells showed only a 12-18% reduction. The observed prevention of the UV-induced reduction in metabolic activity was not simply due to filtering UVR by the P-IC components, as P-IC-mediated reduction of this effect persisted even when P-IC was washed out during UV irradiation. CONCLUSION: This study demonstrated that l-cystine and thiamin are essential for proliferation of epidermal keratinocytes and suggests a novel, UV-protective potential of formulations combining l-cystine and thiamin in growth-limited inter-follicular NHEKs in vitro.


Assuntos
Cistina/farmacologia , Cabelo/crescimento & desenvolvimento , Queratinócitos/citologia , Tiamina/farmacologia , Raios Ultravioleta/efeitos adversos , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/efeitos da radiação , Cabelo/efeitos dos fármacos , Cabelo/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação
16.
Bioorg Med Chem Lett ; 28(22): 3574-3578, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30318439

RESUMO

A series of 4-chloro-2H-thiochromenes featuring nitrogen-containing side chains were designed, synthesized and tested in vitro for their antifungal activities. The results of preliminary antifungal tests showed that most target compounds exhibited good inhibitory activities against Candida albicans, Cryptococcus neoformans, Candida tropicalis. Notably, compounds 10e and 10y showed most potent activity in vitro against a variety of fungal pathogens with low MICs. Meanwhile, low cytotoxicity on mammalian cells has been observed for compounds 10e and 10y in the tested concentrations by the MTT assay. Therefore, the 4-chloro-2H-thiochromenes with nitrogen-containing groups provide new lead structures in the search for novel antifungal agents.


Assuntos
Antifúngicos/síntese química , Desenho de Fármacos , Nitrogênio/química , Tiamina/análogos & derivados , Células A549 , Animais , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Ratos , Relação Estrutura-Atividade , Tiamina/síntese química , Tiamina/farmacologia
17.
Crit Care ; 22(1): 283, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373647

RESUMO

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.


Assuntos
Corticosteroides/uso terapêutico , Ácido Ascórbico/uso terapêutico , Sepse/tratamento farmacológico , Tiamina/uso terapêutico , Corticosteroides/farmacologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Ácido Ascórbico/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Humanos , Hidrocortisona/farmacologia , Hidrocortisona/uso terapêutico , Modelos Biológicos , Tiamina/farmacologia
18.
Front Immunol ; 9: 1778, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30166982

RESUMO

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages and in vivo through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages and in vivo by down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.


Assuntos
Imunidade Inata , Mycobacterium tuberculosis/imunologia , PPAR gama/metabolismo , Tiamina/metabolismo , Tuberculose/imunologia , Tuberculose/metabolismo , Animais , Biomarcadores , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Imunofenotipagem , Metabolismo dos Lipídeos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Tiamina/farmacologia , Tuberculose/microbiologia
19.
Molecules ; 23(6)2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29914147

RESUMO

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn't affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 µg/mL and 2 µg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.


Assuntos
Glicólise/efeitos dos fármacos , Ácido Láctico/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Tiamina/farmacologia , Anaerobiose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7
20.
Eur Rev Med Pharmacol Sci ; 22(10): 3261-3273, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29863274

RESUMO

OBJECTIVE: The water-soluble vitamin, thiamine forms an important part of the diet because of its role in the energy metabolism. The protective effects of thiamine against diabetic vascular complications have been well documented. However, slower absorption and reduced bioavailability is a major limiting factor for its clinical use. To overcome this issue, lipid-soluble derivatives of thiamine (allithiamines) was developed. Among the many synthetic lipophilic derivatives of thiamine, benfotiamine (BFT) is regarded as the first choice based on its safety and clinical efficacy data. BFT facilitates the action of thiamine diphosphate, a cofactor for the enzyme transketolase. The activation of transketolase enzyme accelerates the precursors of advanced glycation end products (AGEs) towards the pentose phosphate pathway thereby reducing the production of AGEs. The reduction in AGEs subsequently decreases metabolic stress which benefits vascular complications seen in diabetes. The effects of BFT on the AGE-dependent pathway is well established. However, several studies have shown that BFT also modulates pathways other than AGE such as arachidonic acid (AA), nuclear transcription Factor κB (NF-κß), protein kinase B, mitogen-activated protein kinases (MAPK) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways. In the present review, we have comprehensively reviewed all the molecular targets modulated by BFT to provide mechanistic perspective to highlight its pleiotropic effects.


Assuntos
Angiopatias Diabéticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Tiamina/análogos & derivados , Animais , Humanos , Tiamina/farmacologia , Tiamina/uso terapêutico
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