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1.
Food Chem ; 317: 126458, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109656

RESUMO

A kinetic model for Maillard reaction (MR) model system of d-glucose and l-lysine was established; activation energy (Ea) of each step was calculated. Potential generation pathways of furosine and pyrraline were a combination of either 3-deoxyglucosone (3-DG) or methylglyoxal (MG) with l-lysine. Ea value for furosine generated through 3-DG pathway was 81.70 ± 14.01 kJ mol-1, which was significantly higher than that through MG pathway (52.08 ± 4.48 kJ mol-1). As for pyrraline, Ea for the 3-DG pathway (53.45 ± 4.02 kJ mol-1) was significantly lower than that through the MG pathway (110.22 ± 18.77 kJ mol-1). Results of the kinetic study indicated that furosine was preferred to be generated through the MG pathway since MG is more likely to react with each other and form a furan ring as a precursor of furosine. Pyrraline was more easily to be generated from the 3-DG pathway through cyclization of 1,4-dicarbonyl compounds to pyrrole.


Assuntos
Glucose/química , Lisina/análogos & derivados , Lisina/química , Reação de Maillard , Norleucina/análogos & derivados , Pirróis/química , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Cinética , Norleucina/química , Aldeído Pirúvico/química
2.
J Agric Food Chem ; 67(46): 12863-12874, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31670949

RESUMO

A comprehensive quantitative characterization of Maillard reaction products was carried out for conventional (CON) and lactose-hydrolyzed (LH) ultrahigh temperature (UHT) milk during storage at 20, 30, and 40 °C for 1 year. The accumulation of 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in LH-UHT milk ranged from 20-fold (at 20 °C) to 44-fold (at 40 °C) higher than that in CON-UHT milk. High temperature storage (40 °C) significantly accelerated the accumulation of 3-DG, 3-DGal, and 5-hydroxymethyl furfural but not the majority of the analyzed advanced glycation endproducts (AGEs). The concentrations of major AGEs including N-ε-carboxymethyllysine (CML), N-ε-carboxyethyllysine (CEL), methylglyoxal-hydroimidazolone isomers (MG-H1/H3), glyoxal-hydroimidazolone isomers (G-H1/H3), and G-H2 detected in CON milk during storage were in the range 12-700, 1-14, 8-45, 4-13, and 1-30 µM, respectively, while they were 30-570, 2-88, 17-150, 9-20, and 5-34 µM, respectively, in LH milk. Pyrraline, S-(carboxymethyl)cysteine (CMC), and glyoxal-lysine dimer were detected in lower levels, while MG-H2, methylglyoxal-lysine dimer, argpyrimidine, glyoxal-lysine-amide, glycolic acid-lysine-amide, and pentosidine were not detected in any of the milk samples. This work demonstrates for the first time that five of the analyzed AGEs (CML, CEL, MG-H1/H3, G-H1/H3, and G-H2) could be selected as markers for evaluation of the extent of the Maillard reaction in UHT milk. These results contribute to a better understanding of how Maillard reactions progress during storage of UHT milk and can be used to develop strategies to inhibit Maillard reactions in LH milk.


Assuntos
Produtos Finais de Glicação Avançada/análise , Lactose/química , Leite/química , Animais , Bovinos , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Armazenamento de Alimentos , Galactose/análogos & derivados , Galactose/análise , Isomerismo , Lisina/análogos & derivados , Lisina/análise , Reação de Maillard , Aldeído Pirúvico/análise , Temperatura
3.
PLoS One ; 14(7): e0217712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306426

RESUMO

Glycoconjugation to target the Warburg effect provides the potential to enhance selective uptake of anticancer or imaging agents by cancer cells. A Warburg effect targeting group, rationally designed to facilitate uptake by glucose transporters and promote cellular accumulation due to phosphorylation by hexokinase (HK), has been synthesised. This targeting group, the C2 modified glucose analogue 2-(2-[2-(2-aminoethoxy)ethoxy]ethoxy)-D-glucose, has been conjugated to the fluorophore nitrobenzoxadiazole to evaluate its effect on uptake and accumulation in cancer cells. The targeting vector has demonstrated inhibition of glucose phosphorylation by HK, indicating its interaction with the enzyme and thereby confirming the potential to facilitate an intracellular trapping mechanism for compounds it is conjugated with. The cellular uptake of the fluorescent analogue is dependent on the glucose concentration and is so to a greater extent than is that of the widely used fluorescent glucose analogue, 2-NBDG. It also demonstrates selective uptake in the hypoxic regions of 3D spheroid tumour models whereas 2-NBDG is distributed primarily through the normoxic regions of the spheroid. The increased selectivity is consistent with the blocking of alternative uptake pathways.


Assuntos
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Desoxiglucose/análogos & derivados , Sistemas de Liberação de Medicamentos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucose , Hexoquinase/metabolismo , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Neoplasias , 4-Cloro-7-nitrobenzofurazano/farmacocinética , 4-Cloro-7-nitrobenzofurazano/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Desoxiglucose/farmacocinética , Desoxiglucose/farmacologia , Glucose/farmacocinética , Glucose/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
4.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340585

RESUMO

The stems of Dendrobium loddigesii, a Chinese herb, are often used to treat diabetes and its polar extract is rich in shihunine, a water-soluble Orchidaceae alkaloid, but little is known about the anti-diabetes effects and mechanism of shihunine. This study investigated the anti-diabetic effect of a shihunine-rich extract of D. loddigesii (DLS) based on 3T3-L1 cells and db/db mice. The underlying mechanisms were primarily explored using Western blot analysis and immunohistochemical staining. The 3T3-L1 cell experiments showed that DLS can reduce the intracellular accumulation of oil droplets as well as triglycerides (p < 0.001) and promote the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2deoxyglucose (2-NBDG) uptake of 3T3-L1 cells (p < 0.001). The animal experiments confirmed that after 8 weeks of DLS treatment, the body weight, fasting blood sugar, and serum lipid levels of mice were significantly lowered, and the oral glucose tolerance test and serum insulin level were significantly improved compared to the no-treatment diabetes mellitus group. Further histomorphology observation led to the conclusion that the quantities of islet cells were significantly increased and the increase in adipose cell size was significantly suppressed. The immunohistochemical test of pancreatic tissue revealed that DLS inhibited the expression of cleaved cysteine aspartic acid-specific protease 3 (cleaved caspase-3). Western blot experiments showed that DLS had agonistic effects on adenosine monophosphate (AMP)-activated protein kinase phosphorylation (p-AMPK) and increased the expression levels of peroxisome proliferator-activated receptor α (PPARα) and glucose transporter 4 (GLUT4) in liver or adipose tissues. These data suggest that the shihunine-rich extract of D. loddigesii is an anti-diabetic fraction of D. loddigesii. Under our experimental condition, DLS at a dose of 50 mg/kg has good anti-diabetic efficacy.


Assuntos
Glicemia/efeitos dos fármacos , Dendrobium/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Pirrolidinas/farmacologia , Células 3T3-L1 , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Transporte Biológico , Glicemia/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Jejum , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/isolamento & purificação , Lactonas/isolamento & purificação , Gotículas Lipídicas/química , Gotículas Lipídicas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , PPAR alfa/genética , PPAR alfa/metabolismo , Extratos Vegetais/química , Caules de Planta/química , Pirrolidinas/isolamento & purificação , Transdução de Sinais , Triglicerídeos/antagonistas & inibidores , Triglicerídeos/metabolismo
5.
Mol Biol Rep ; 46(5): 4799-4808, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228040

RESUMO

Maintenance of glucose homeostasis is reciprocally regulated by insulin and glucagon-like peptide-1 (GLP-1). We previously reported that GLP-1 secretion in response to an oral glucose load was impaired following an administration of 3-deoxyglucosone (3DG), an independent factor associated with the development of pre-diabetes. Here we investigated the effects of 3DG on insulin signaling and insulin-induced GLP-1 secretion under high-glucose conditions in the enteroendocrine L cell line STC-1. STC-1 cells were exposed to 3DG (80, 300, and 1000 ng/ml) in the presence of 10-7 M insulin and 25 mM glucose. GLP-1 secretion was determined by ELISA, glucose uptake was monitored with 2-NBDG (2-(N(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose), glucose consumption was detected by glucoseoxidase, and protein expression of insulin signaling molecules was examined by western blot. Results showed a decrease in insulin-induced GLP-1 secretion and insulin receptor phosphorylation after 3DG treatment. Concomitantly, 3DG treatment inhibited insulin-induced phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway activation. In the presence, but not absence, of insulin, 3DG treatment decreased insulin-stimulated glucose consumption. Inhibition of PI3K with Wortmannin attenuated insulin-induced increment in glucose transporter 2 (GLUT2) expression and 2-NBDG uptake. Accordingly, insulin-induced increase in GLUT2 expression and 2-NBGD uptake was significantly inhibited by 3DG treatment. 3DG-mediated reduction in GLUT2 expression contributes to the attenuation of insulin-induced GLP-1 secretion under high-glucose conditions in part through the insulin-PI3K/Akt/GLUT2 pathway in STC-1 cells. We conclude that 3DG interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in STC-1 cells.


Assuntos
Desoxiglucose/análogos & derivados , Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/biossíntese , Glucose/metabolismo , Insulina/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Desoxiglucose/metabolismo , Transportador de Glucose Tipo 2/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/metabolismo
6.
J Agric Food Chem ; 67(20): 5874-5881, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31050431

RESUMO

Dicarbonyl compounds such as methylglyoxal (MGO) and 3-deoxyglucosone (3-DG) are formed via caramelization and the Maillard reaction in food during heating or in vivo as byproducts of glycolysis. Recently, it was shown that creatine, an amino compound linked to the energy metabolism in vertebrate muscle, reacts rapidly with methylglyoxal under physiological conditions to form N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr), a methylglyoxal-derived hydroimidazolone of creatine. Based on the observation that heated meat contains only small amounts of MGO and 3-DG when compared to many other foodstuffs, the aim of this study was to investigate a possible reaction of creatine with 3-DG and MGO in meat. From incubation mixtures consisting of 3-DG and creatine, a new hydroimidazolone of creatine, namely N-(4-butyl-1,2,3-triol-5-oxo-1-imidazolin-2-yl)sarcosine (3-DG-HCr), was isolated and characterized via spectroscopic means. To quantitate 3-DG-HCr and MG-HCr, meat and fish products were analyzed via HPLC-MS/MS using isotopically labeled standard material. Whereas samples of raw fish and meat contained only trace amounts of the hydroimidazolones (below 5 µg/kg), up to 28.3 mg/kg MG-HCr and up to 15.3 mg/kg 3-DG-HCr were found in meat and fish products. The concentrations were dependent on the heat treatment and presumably on the smoking process. In comparison to the lysine and arginine derivatives CEL, pyrraline, and MG-H1, the derivatization rate of creatine as MG-HCr and 3-DG-HCr was higher than of lysine and arginine, which clearly demonstrates the 1,2-dicarbonyl scavenging properties of creatine in meat.


Assuntos
Creatina/química , Desoxiglucose/análogos & derivados , Imidazóis/química , Carne/análise , Aldeído Pirúvico/química , Animais , Arginina/química , Bovinos , Galinhas , Cromatografia Líquida de Alta Pressão , Culinária , Desoxiglucose/química , Temperatura Alta , Lisina/química , Reação de Maillard , Suínos , Espectrometria de Massas em Tandem
7.
Mol Med Rep ; 19(6): 5015-5022, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059088

RESUMO

Sweet taste receptors (STRs) expressed on ß­cells stimulate insulin secretion in response to an increase in the circulating level of glucose, maintaining glucose homeostasis. 3­Deoxyglucosone (3DG), a highly reactive α­dicarbonyl compound, has been previously described as an independent factor associate with the development of prediabetes. In our previous study, pathological plasma levels of 3DG were induced in normal rats with a single intravenous injection of 50 mg/kg 3DG, and an acute rise in circulating 3DG induced glucose intolerance by impairing the function of pancreatic ß­cells. The present study aimed to investigate whether the deleterious effects of pathological plasma levels of 3DG on ß­cell function and insulin secretion were associated with STRs. INS­1 cells, an in vitro model to study rat ß­cells, were treated with various concentrations of 3DG (1.85, 30.84 and 61.68 mM) or lactisole (5 mM). Pancreatic islets were collected from rats 2 h after a single intravenous injection of 50 mg/kg 3DG + 0.5 g/kg glucose. The insulin concentration was measured by ELISA. The protein expression levels of components of the STR signaling pathways were determined by western blot analysis. Treatment with 3DG and 25.5 mM glucose for 1 h significantly reduced insulin secretion by INS­1 cells, which was consistent with the phenotype observed in INS­1 cells treated with the STR inhibitor lactisole. Accordingly, islets isolated from rats treated with 3DG exhibited a significant reduction in insulin secretion following treatment with 25.5 mM glucose. Furthermore, acute exposure of INS­1 cells to 3DG following treatment with 25.5 mM glucose for 1 h significantly reduced the protein expression level of the STR subunit taste 1 receptor member 3 and its downstream factors, transient receptor potential cation channel subfamily M member 5 and glucose transporter 2. Notably, islet tissues collected from rats treated with 3DG exhibited a similar downregulation of these factors. The present results suggested that acute exposure to pathologically relevant levels of 3DG in presence of high physiological levels of glucose decreased insulin secretion from ß­cells by, at least in part, downregulating the STR signaling pathway.


Assuntos
Desoxiglucose/análogos & derivados , Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Derivados de Benzeno/farmacologia , Células Cultivadas , Desoxiglucose/farmacologia , Regulação para Baixo/efeitos dos fármacos , Transportador de Glucose Tipo 2/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Canais de Cátion TRPM/metabolismo
8.
Toxicol In Vitro ; 60: 76-86, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31100377

RESUMO

Apoptosis of neutrophils is an essential checkpoint for the resolution of inflammation by shutting down the deleterious functions of these immune cells. This study investigated the role of anhydroglucitol-core gallotannins (ACGs) in apoptosis increase of human blood neutrophils treated by the hot water extract from red maple buds (RMB). Fractions obtained by liquid-liquid partitioning (ethyl acetate, butanol and water-remaining fractions) of the hot water extract from RMB were assessed for their effects on neutrophil viability by using flow cytometry. These fractions were then phytochemically analyzed to investigate the ability of major compounds to induce neutrophil apoptosis individually. Ethyl acetate and butanol fractions that contained the major ACGs ginnalin A, ginnalin 3,6 and ginnalin C stimulated the apoptosis of neutrophils. The three ACGs at 100 µM significantly increased the rate of the late apoptotic cells. When differentially combined, these ACGs have additive or antagonist effects. These effects are related to the concentrations of the constituents in the mixtures studied, especially so for ginnalin C. GinA increased FADD, phospho-Rad17, SMAC/Diablo and cytochrome C, while decreasing the anti-apoptotic protein catalase. These compounds could be useful for the development of novel therapeutic approaches that facilitate resolution of neutrophil-mediated inflammatory diseases.


Assuntos
Acer , Desoxiglucose/análogos & derivados , Desoxiglucose/farmacologia , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Neutrófilos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Cultivadas , Flores , Humanos , Taninos Hidrolisáveis , Extratos Vegetais/farmacologia
9.
Food Chem ; 289: 320-327, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955619

RESUMO

The role of Reactive Carbonyl Species (RCS) derived from the Maillard reaction and ascorbic acid degradation on brown color formation was investigated in orange juice during storage. Eight RCS were monitored in aseptic juice over an 8-week period under refrigerated (4 °C) and accelerated conditions (35 °C). Significant changes in RCS concentrations were reported and positively correlated with color formation. Recombination experiments demonstrated the significant role of 3-deoxyglucosone and acetol on color formation as well as their interactions with glyoxal and methylglyoxal that lead to an increase in browning. Isotopic enrichment techniques further identified fructose as the main precursor of RCS, indicating the important role of Maillard reaction as a mechanism of non-enzymatic browning during orange juice storage. Finally, among the amino acids, tryptophan and glutamine showed the largest percentage losses in orange juice during storage and were reported to significantly impact the RCS composition and color formation.


Assuntos
Citrus sinensis/química , Sucos de Frutas e Vegetais/análise , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão , Citrus sinensis/metabolismo , Cor , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Armazenamento de Alimentos , Frutose/química , Glioxal/análise , Glioxal/química , Reação de Maillard , Espectrometria de Massas , Espectrofotometria Ultravioleta , Temperatura
10.
Food Chem ; 290: 187-195, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000036

RESUMO

3-Deoxyglucosone (3-DG) is a metabolite from sugar degradation obtained by the Maillard reaction. It is an important precursor compound in Strecker reactionism that directly leads to known beer aging indicators and can influence the final sensory beer quality. However, the conditions of 3-DG formation in the malting process have not yet been described. To investigate the reaction pathways of 3-DG formation, we varied the composition of reactants (sugars, amino acids) by using different malting modification levels (germination time 5-7 d; steeping degree 42-45%; germination temperature 12-14 °C); final kilning temperature (60 °C to 100 °C). After its derivatization with ortho-phenylenediamine, we analyzed 3-DG with HPLC-UV. 3-DG concentration was between 5 and 120 µmol/100 g dry weight. The formation of 3-DG increased for high malt modification levels and high final kilning temperature. The abundant formation of 3-DG in the malting process is already comparable to the occurred brewing process concentration.


Assuntos
Desoxiglucose/análogos & derivados , Manipulação de Alimentos/métodos , Aminoácidos/análise , Cerveja/análise , Cromatografia Líquida de Alta Pressão , Desoxiglucose/química , Reação de Maillard , Monossacarídeos/análise , Fenilenodiaminas/análise , Espectrofotometria Ultravioleta , Temperatura
11.
J Agric Food Chem ; 67(18): 5197-5203, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017427

RESUMO

Melanoidins are formed in foods during processing through the Maillard reaction between carbohydrates and amino compounds. The aim of this study was to draw conclusions about the formation mechanism and the structure of melanoidins formed at low water contents and low temperatures. In the Maillard reaction of d-glucose and γ-aminobutyric acid at low water contents 3-deoxyglucosone is the most important intermediate. Therefore, we used the reaction of 3-deoxyglucosone with γ-aminobutyric acid or ß-alanine as a simplified model system. The degradation of 3-deoxyglucosone and the color formation of the formed melanoidins were determined. In addition, the reaction mixture was analyzed with high-resolution mass spectrometry and a Kendrick analysis was applied. Oligomers consisting of up to four molecules of 3-deoxyglucosone and three amino acids and their respective dehydration products with furanoidic structure were detected. The melanoidin structure of C-C linked monomeric units postulated by Kroh et al. could be confirmed.


Assuntos
Desoxiglucose/análogos & derivados , Ácido gama-Aminobutírico/química , Aminoácidos/química , Desoxiglucose/química , Glucose/química , Cinética , Reação de Maillard , Estrutura Molecular , Polímeros/química
12.
Clin Nucl Med ; 44(5): 386-393, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30888989

RESUMO

PURPOSE: Insulin resistance is a key feature of the metabolic syndrome and type 2 diabetes, in which noninvasive assessment is not currently allowed by any methodology. We previously validated an iodinated tracer of glucose transport (6DIG) and a new methodology for the in vivo quantification of cardiac insulin resistance in rodents. The aim of this study was to investigate the safety, biodistribution, and radiation dosimetry of this method using I-6DIG in 5 healthy and 6 diabetic volunteers. METHODS: The collection of adverse effects (AEs) and medical supervision of vital parameters and biological variables allowed the safety evaluation. Biodistribution was studied by sequentially acquiring whole-body images at 1, 2, 4, 8, and 24 hours postinjection. The total number of disintegrations in each organ normalized to the injected activity was calculated as the area under the time-activity curves. Dosimetry calculations were performed using OLINDA/EXM. RESULTS: No major adverse events were observed. The average dose corresponding to the 2 injections of I-6DIG used in the protocol was 182.1 ± 7.5 MBq. A fast blood clearance of I-6DIG was observed. The main route of elimination was urinary, with greater than 50% of urine activity over 24 hours. No blood or urine metabolite was detected. I-6DIG accumulation mostly occurred in elimination organs such as kidneys and liver. Mean radiation dosimetry calculations indicated an effective whole-body absorbed dose of 3.35 ± 0.57 mSv for the whole procedure. CONCLUSIONS: I-6DIG was well tolerated in human with a dosimetry profile comparable to that of other commonly used iodinated tracers, thereby allowing further clinical development of the tracer.


Assuntos
Desoxiglucose/análogos & derivados , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Desoxiglucose/administração & dosagem , Desoxiglucose/efeitos adversos , Desoxiglucose/farmacocinética , Feminino , Humanos , Masculino , Doses de Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Eliminação Renal , Distribuição Tecidual
13.
Food Funct ; 10(4): 2022-2029, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30906941

RESUMO

During the conventional production of brown fermented milk (BFM), unhealthy substances (3-deoxyglucosone (3-DG), methylglyoxal (MGO), and 5-hydroxymethylfurfural (HMF)) are generated during the Maillard browning step. Here, an alternative browning process based on the hydrolysis of endogenous lactose was established. Compared with the conventional process, 3-DG and HMF were decreased by 5.91 mg kg-1 and 0.39 mg kg-1 in the brown milk base under the alternative browning process, and thereafter, 3-DG and HMF were decreased by 54.5% and 65.0% in BFM. Investigation into the formation of 3-DG, MGO, and HMF in different chemical models showed that different sugars lead to different Maillard reaction products and browning rates, contributing to the mitigation of 3-DG and HMF. Apart from the mitigation of unhealthy Maillard compounds, hydrolyzing lactose and avoiding the addition of external glucose make the alternative browning process a theoretical and practical basis for improving the quality and safety of BFM.


Assuntos
Desoxiglucose/análogos & derivados , Furaldeído/análogos & derivados , Lactose/química , Leite/química , Animais , Bovinos , Desoxiglucose/análise , Fermentação , Furaldeído/análise , Glucose/química , Temperatura Alta , Hidrólise , Reação de Maillard
14.
Carbohydr Res ; 475: 48-55, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825721

RESUMO

Six different types of O-benzyl protected proline derivatives have been synthesized from D-glycals and 2C-formyl-glycals. One of the di-O-benzyl protected proline derivatives has been utilized for the synthesis of polysubstituted pyrrolizidines via [3 + 2] cycloaddition in a stereoselective manner. Further, we also report on the stereoselective synthesis of biologically active 1C-aryl/alkyl pyrrolidines i.e. 4-epi-radicamine B, 4-epi-radicamine A, 1C-butyl and 1C-methyl pyrrolidines through double reductive amination of a variety of D-glucal derived diketones with p-methoxybenzylamine.


Assuntos
Desoxiglucose/análogos & derivados , Prolina/síntese química , Pirróis/síntese química , Desoxiglucose/química , Estrutura Molecular , Prolina/química , Pirróis/química
16.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1106-1107: 19-25, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30639946

RESUMO

The presence of α­dicarbonyl compounds (α-DCs) in vivo has been associated with the development of complications of diabetes mellitus (DM) and also with other chronic diseases. Therefore, quantitative analysis of α-DCs in body fluids is crucial to understand their roles in the formation of these chronic diseases. We established in this study a practical HPLC-UV method to measure 3­deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane­2,3­dione (PD) in blood plasma using 4­(2,3­dimethyl­6­quinoxalinyl)­1,2­benzenediamine (DQB) as a derivatizing reagent. The derivatizing reaction could be carried out quickly under mild conditions and the HPLC determination is simple, sensitive, and easy to operate. The recoveries of the α-DCs are between 85.26% and 110.20% (intra-day) and 87.25% and 103.18% (inter-day); the RSDs are between 1.28% and 5.69% (intra-day) and 2.26% and 6.34% (inter-day). We found the plasma levels of 3-DG, GO, and MGO in the diabetic patients are all significantly higher than those in healthy subjects. The results also show that the contents of GO and MGO in diabetic nephropathy (DN) patients are both significantly higher than those in simple T2DM patients. Moreover, it is found for the first time that the plasma level of GO might be a potential predictor of DN. The developed method would be useful for the measurements of the plasma α-DCs and the data acquired could be informative in the diagnosis of DM complications.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Idoso , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Desoxiglucose/análogos & derivados , Desoxiglucose/sangue , Nefropatias Diabéticas/diagnóstico , Diacetil/sangue , Feminino , Glioxal/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Aldeído Pirúvico/sangue
17.
Chem Res Toxicol ; 32(2): 304-311, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30640474

RESUMO

Glucose degradation products (GDPs) are formed from glucose and other reducing sugars during heat treatment, for example, in heat-sterilized peritoneal dialysis fluids or foods. Because of their reactive mono- and dicarbonyl structure, they react readily with proteins, resulting in the formation of advanced glycation end products (AGEs), loss of protein functionality, and cytotoxicity. Among the GDPs, 3,4-dideoxyglucosone-3-ene (3,4-DGE) exerts the strongest effects despite its relatively low concentration levels. The goal of the present study was therefore to identify the structure of specific protein modifications deriving from 3,4-DGE. A nonapeptide containing the reactive amino acids lysine, arginine, and cysteine was incubated with 3,4-DGE and the dominant GDPs 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in concentrations as present in peritoneal dialysis fluids (235 µM 3-DG, 100 µM 3-Gal, and 11 µM 3,4-DGE). Glycation rate and product formation were determined by ultra-HPLC-MS/MS (UHPLC-MS/MS). 3,4-DGE showed the strongest glycation activity. After 2 h of incubation, 3,4-DGE had modified 57% of the nonapeptide, whereas 3-DG had modified only 2% and 3-DGal had modified 29% of the peptide. A stable 3,4-DGE-derived cysteine modification was isolated. Its structure was determined by comprehensive NMR and MS experiments to be [6-hydroxy-2-(hydroxymethyl)-5-oxo-5,6-dihydro-2 H-pyran-3-yl]-cysteine (HHPC), which represents a novel cysteine-AGE derived from 3,4-DGE. The results indicate that 3,4-DGE might contribute to a severe loss of protein functionality by forming cysteine-specific AGEs, such as HHPC.


Assuntos
Cisteína/química , Cistina/análise , Soluções para Diálise/química , Piranos/análise , Pironas/química , Cromatografia Líquida de Alta Pressão , Cistina/química , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Galactose/análogos & derivados , Galactose/análise , Produtos Finais de Glicação Avançada/análise , Peptídeos/química , Piranos/química , Espectrometria de Massas em Tandem
18.
Nephrology (Carlton) ; 24(9): 943-950, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30407693

RESUMO

AIM: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. METHODS: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. RESULTS: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. CONCLUSION: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.


Assuntos
Nefropatias Diabéticas/sangue , Falência Renal Crônica/sangue , Aldeído Pirúvico/sangue , Insuficiência Renal Crônica/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Desoxiglucose/análogos & derivados , Desoxiglucose/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Feminino , Humanos , Japão , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Fatores de Tempo , Regulação para Cima
19.
Bioorg Med Chem ; 26(22): 5922-5933, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420329

RESUMO

Boron neutron capture therapy (BNCT) is one of the radiotherapies that involves the use of boron-containing compounds for the treatment of cancer. Boron-10 (10B) containing compounds that can accumulate in tumor tissue are expected to be suitable agents for BNCT. We report herein on the design and synthesis of some new BNCT agents based on a d-glucose scaffold, since glycoconjugation has been recognized as a useful strategy for the specific targeting of tumors. To introduce a boryl group into a d-glucose scaffold, we focused on the hydroboration of d-glucal derivatives, which have a double bond between the C1 and C2 positions. It was hypothesized that a C-B bond could be introduced at the C2 position of d-glucose by the hydroboration of d-glucal derivatives and that the products could be stabilized by conversion to the corresponding boronic acid ester. To test this hypothesis, we prepared some 2-boryl-1,2-dideoxy-d-glucose derivatives as boron carriers and evaluated their cytotoxicity and cellular uptake activity to cancer cells, especially under hypoxic conditions.


Assuntos
Terapia por Captura de Nêutron de Boro , Boro/farmacologia , Desoxiglucose/análogos & derivados , Desenho de Fármacos , Monossacarídeos/farmacologia , Células A549 , Boro/química , Sobrevivência Celular/efeitos dos fármacos , Desoxiglucose/química , Desoxiglucose/farmacologia , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Estrutura Molecular , Monossacarídeos/síntese química , Monossacarídeos/química , Relação Estrutura-Atividade
20.
Biochemistry (Mosc) ; 83(11): 1358-1368, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30482147

RESUMO

3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to ß-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1ß in blood plasma as well as the ROS level and content of TNF-α and IL-1ß in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1ß in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1ß), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1ß and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1ß levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of ß-cell dysfunction.


Assuntos
Colo/metabolismo , Desoxiglucose/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Animais , Colo/patologia , Desoxiglucose/farmacocinética , Desoxiglucose/farmacologia , Células Secretoras de Insulina/patologia , Permeabilidade , Ratos , Ratos Sprague-Dawley
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