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1.
Food Chem ; 306: 125626, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31627083

RESUMO

The effect of glycine betaine (GB) on chilling injury (CI)-induced pericarp browning in 'Nanguo' pears was investigated during shelf life at 20 °C after storage at 0 °C for 120 d. GB treatment alleviated the severity of browning in 'Nanguo' pears as represented by lower browning index (BI) and browning incidence. Membrane lipid peroxidation in GB-treated fruit was lower than that in the control, and membrane integrity was maintained in good condition. The activities and expression of ascorbate peroxidase (APX), catalase (CAT), and superoxide dismutase (SOD) were higher in GB-treated fruit than in control fruit. Furthermore, significantly higher proline content, proline synthesis key enzyme activities, and gene expression were observed in the treated fruit, including ornithine d-aminotransferase (OAT) and Δ1-pyrroline-5-carbox-ylate synthetase (P5CS), which were consistent with the browning tendency. In a nutshell, GB treatment can effectively alleviate pericarp browning of cold-stored 'Nanguo' pears by regulating antioxidant enzymes and proline metabolism.


Assuntos
Betaína/farmacologia , Glicina/farmacologia , Pyrus/metabolismo , Antioxidantes/metabolismo , Catalase/metabolismo , Temperatura Baixa , Frutas/metabolismo , Peroxidase/metabolismo , Prolina/metabolismo , Pyrus/efeitos dos fármacos , Superóxido Dismutase/metabolismo
2.
Cell Physiol Biochem ; 53(5): 851-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714043

RESUMO

BACKGROUND/AIMS: The growth promoting effect of lysine and betaine as well as the expression of candidate genes reflecting their efficacy, such as ghrelin, leptin, Growth Hormone Secretagogue Receptor (GHS-R), Insulin like Growth Factor (IGF- 1) and Growth Hormone Releasing Hormone (GHRH) was examined in Labeo rohita fingerlings. METHODS: One hundred eighty healthy juveniles from a homologous population were randomly distributed to 15 rectangular tanks of 150 litres capacity. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. At the end of trial, the growth parameters such as weight gain, SGR, PER were estimated from the weight of the triplicate groups. The digestive, metabolic and antioxidant enzymes were analysed using spectrophotometric methods. The intestine, brain and liver were sampled from the treatments and expression of different genes ghrelin, leptin, GHSR, IGF-1 and GHRH was also performed by realtime PCR. RESULTS: A significant (P<0.05) increase in weight gain, SGR, PER and lowest FCR was found in T4 group which was significantly (p < 0.05) different from other experimental groups. The highest mRNA expression levels of expression were found in T4 group which was similar to that of ghrelin gene mRNA of T2 group. The significantly (p<0.05) highest GHSR, GHRH and IGF-1 gene expression levels were found in T4 treatment group compared to other groups. CONCLUSION: The present study reveals that the lysine and betaine stimulate growth and expression of ghrelin GHRH, GHS-R and IGF-1 genes. The increase of IGF-I mRNA expression with lysine and betaine supplementation revealed that these compounds act as growth modulators. However, lysine was found to be a more potent modulator of growth compared to betaine.


Assuntos
Betaína/farmacologia , Cyprinidae/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lisina/farmacologia , Ração Animal , Animais , Catalase/metabolismo , Cyprinidae/crescimento & desenvolvimento , Grelina/genética , Grelina/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Leptina/genética , Leptina/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Superóxido Dismutase/metabolismo
3.
J Therm Biol ; 83: 80-86, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331529

RESUMO

This study investigated the effects of floor space and betaine supplementation on the nutrient digestibility and performance of laying quail, at an advanced stage of production, in a tropical environment. In total, 408 laying quail (23 weeks old) were distributed in 3 × 2 factorial arrangements with four replicates. The first factor was floor space (250 cm2 [FS-1], 221 cm2 [FS-2], and 200 cm2 per bird [FS-3]) by allocating 15, 17, and 19 birds per cage (cage size: 3750 cm2). The second factor was betaine supplementation, administered at levels of 0 (Control) and 0.12% (Betaine). The birds were housed under a natural, tropical environment that was outside the predominant thermoneutral zone, indicating heat stress conditions. Interactions were found between floor space and betaine on crude fiber digestibility, egg production, and eggshell thickness, with the highest values being yielded in FS-2 group supplemented with betaine. Reducing the floor space to 200 cm2 negatively affected nutrient digestibility and performance. The birds kept in FS-3 had lower (P < 0.05) dry matter, crude protein, crude fat, and calcium digestibility values than those kept in FS-1 and FS-2. Birds housed in FS-2 exhibited higher egg weight than those in FS-3 (P < 0.05), although they did not differ from those in FS-1. Furthermore, a lower eggshell weight in FS-3, compared with FS-1 and FS-2, was observed (P < 0.01). Betaine supplementation enhanced the dry matter, crude protein, crude fat, crude ash, and calcium digestibility values (P < 0.05). Accordingly, betaine improved feed intake, egg weight, feed conversion, and protein and energy efficiency ratios (P < 0.01). Betaine also resulted in higher albumen, yolk, and eggshell weights (P < 0.01). In conclusion, a floor space of 221 cm2, combined with betaine supplementation at 0.12%, can be applied for raising quail under high environmental temperatures.


Assuntos
Betaína/farmacologia , Fármacos Gastrointestinais/farmacologia , Temperatura Alta , Abrigo para Animais , Aves Domésticas/fisiologia , Codorniz/fisiologia , Animais , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Ovos/normas , Oviparidade/efeitos dos fármacos , Clima Tropical
4.
EBioMedicine ; 45: 432-446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31255657

RESUMO

BACKGROUND: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. METHODS: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. FINDINGS: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. INTERPRETATION: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).


Assuntos
Betaína/farmacologia , Colina Desidrogenase/genética , Psicotrópicos/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Genótipo , Humanos , Japão , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metanfetamina/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Locos de Características Quantitativas , Esquizofrenia/genética , Esquizofrenia/fisiopatologia
5.
Poult Sci ; 98(10): 4457-4464, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162616

RESUMO

Infectious bursal disease virus (IBDV) often infects young chickens and causes severe immunosuppression and inflammatory injury. Betaine is an antiviral and anti-inflammatory ingredient that may exert functions through epigenetic regulation. However, the effects of betaine on an IBDV-induced bursal injury and their underlying mechanisms have not been investigated. In this study, betaine was supplemented to the drinking water of newly hatched commercial broilers for 3 wk. Afterward, the chickens were infected with the IBDV. After 5 D of infection, the bursal lesions were examined. The mRNA expression levels of IBDV VP2 gene, pro-inflammatory cytokines, and interferons were detected. Furthermore, the 5-methylcytosine level of the CpG island in the promoter region of IL-6 and interferon regulatory factor 7 (IRF7) were determined. The IBDV induced the depletion of lymphocytes and inflammation in the bursal follicles. IBDV infection considerably elevated the mRNA levels of VP2, IL-6, types I (IFNα and IFNß) and II (IFNγ) interferons, and IRF7. The CpG island methylation in the promoter regions of IL-6 and IRF7 were substantially decreased after IBDV infection. Betaine administration attenuated the IBDV-induced bursal lesions. Meanwhile, the IBDV-induced mRNA expression levels of IL-6, IFNß, and IRF7 were suppressed by betaine consumption. Furthermore, the hypomethylation effects of IBDV infection to the promoter regions of IL-6 and IRF7 genes were eliminated and relieved by betaine administration. Our results indicated that the IBDV-induced expression levels of IL-6 and IRF7 genes are associated with the suppression of methylation in the promoter region. Betaine administration through drinking water may alleviate the IBDV-induced bursal injury via epigenetic regulation.


Assuntos
Antivirais/farmacologia , Betaína/farmacologia , Infecções por Birnaviridae/veterinária , Vírus da Doença Infecciosa da Bursa/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Animais , Proteínas Aviárias/metabolismo , Infecções por Birnaviridae/tratamento farmacológico , Infecções por Birnaviridae/virologia , Metilação de DNA , Fator Regulador 7 de Interferon/metabolismo , Interleucina-6/metabolismo , Doenças das Aves Domésticas/virologia , Distribuição Aleatória
6.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 1050-1059, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31140661

RESUMO

The effects of dietary betaine supplementation on growth performance, carcass characteristics, muscle amino acid contents, meat quality, antioxidant capacity, myogenic gene expression and mechanistic target of rapamycin (mTOR) signalling pathway in Cherry Valley ducks were evaluated. A total of 720 1-day-old Cherry Valley ducks were randomly distributed into four groups with six replicates of 30 birds for a 42-day feeding trial. Ducks were fed a basal diet supplemented with 0 (control), 250, 500 or 1,000 mg/kg betaine, respectively. Growth performance was not affected by betaine. Incremental levels of betaine linearly (p < 0.05) increased the breast muscle yield and linearly (p < 0.05) decreased the subcutaneous fat thickness and the abdominal fat yield. The contents of methionine, serine, glycine, glutamate and total non-essential amino acid in breast muscle were linearly (p < 0.05) increased by betaine supplementation. With increasing betaine levels, the drip loss and the content of malondialdehyde (MDA) were linearly (p < 0.05) decreased, and the redness of meat (linear p < 0.05), the activities of catalase (CAT) (linear p < 0.05) and total superoxide dismutase (T-SOD) (linear p < 0.05, quadratic p < 0.05) were increased. Moreover, the myogenic differentiation factor 1 (MyoD1) mRNA expression and the mTOR mRNA expression and protein phosporylation were linearly (p < 0.05) up-regulated, and the myostatin (MSTN) mRNA expression was linearly (p < 0.05) down-regulated by betaine supplementation. Overall, this study indicated that betaine supplementation did not affect the growth performance of Cherry Valley ducks, but could linearly increase some amino acid contents in breast muscle, especially glycine, and increase muscle antioxidant activity to improve meat quality. Moreover, betaine supplementation could improve the breast muscle yield by increasing MyoD1 mRNA expression, decreasing MSTN mRNA expression and regulating mTOR signalling pathway.


Assuntos
Aminoácidos/metabolismo , Betaína/farmacologia , Suplementos Nutricionais , Carne/normas , Músculo Esquelético/crescimento & desenvolvimento , Animais , Antioxidantes/metabolismo , Betaína/administração & dosagem , Patos , Regulação da Expressão Gênica/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
7.
Nanoscale ; 11(21): 10167-10171, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31112182

RESUMO

We have introduced a non-hormonal hyperglycemia treatment strategy by using an injectable glucose-responsive boronic acid- zwitterionic nanogel. The synthesized system, similar to an artificial liver, is capable of storing/releasing glucose at high/low blood glucose concentrations. In vivo performance revealed that the injection of the nanogels can effectively regulate blood glucose in type 1 diabetic rats for at least 6 hours.


Assuntos
Betaína/análogos & derivados , Glicemia/metabolismo , Ácidos Borônicos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hiperglicemia , Nanoestruturas , Animais , Betaína/síntese química , Betaína/química , Betaína/farmacologia , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Géis , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Ratos , Ratos Sprague-Dawley
8.
J Hosp Infect ; 103(1): e92-e96, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30986480

RESUMO

The aim of this study was to investigate the effect of polyhexanide (polyhexamethylene biguanide)-betaine (PHMB-B) compared with 2% chlorhexidine against biofilms of high-risk and/or multidrug-resistant bacterial clones. The minimum inhibitory concentrations of both biocides were determined by microdilution. The effect of PHMB-B and chlorhexidine on biofilm was evaluated by spectrophotometry and cell viability assays. At commercial concentrations, PHMB-B reduced 24 h, 48 h and 1-week biofilms of all pathogens tested. PHMB-B was more active than 2% chlorhexidine against Gram-negative bacterial 24 h and 48 h biofilms and Gram-positive bacterial 7-day biofilms. In summary, the activity of PHMB-B was superior to that of 2% chlorhexidine in those biofilms.


Assuntos
Betaína/farmacologia , Biguanidas/farmacologia , Biofilmes/efeitos dos fármacos , Desinfetantes/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Clorexidina/farmacologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Soluções/farmacologia
9.
Int J Mol Sci ; 20(7)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30935160

RESUMO

Greenhouse hydroponic experiments were conducted using Cd-sensitive (cv. Guiyan1) and Cd-tolerant (cv. Yunyan2) tobacco cultivars to study the ameliorative effects of exogenous glycinebetaine (GB) upon 5 µM Cd stress. The foliar spray of GB markedly reduced Cd concentrations in plants and alleviated Cd-induced soil plant analysis development (SPAD) value, plant height and root length inhibition, with the mitigation effect being more obvious in Yunyan2. External GB markedly reduced Cd-induced malondialdehyde (MDA) accumulation, induced stomatal closure, ameliorated Cd-induced damages on leaf/root ultrastructure, and increased the chlorophyll content and fluorescence parameters of Fo, Fm, and Fv/Fm in both cultivars and Pn in Yunyan2. Exogenous GB counteracted Cd-induced alterations of certain antioxidant enzymes and nutrients uptake, e.g., the depressed Cd-induced increase of superoxide dismutase (SOD) and peroxidase (POD) activities, but significantly elevated the depressed catalase (CAT) and ascorbate peroxidase (APX) activities. The results indicate that alleviated Cd toxicity by GB application is related to the reduced Cd uptake and MDA accumulation, balanced nutrients and antioxidant enzyme activities, improved PSII, and integrated ultrastructure in tobacco plants.


Assuntos
Betaína/farmacologia , Cádmio/toxicidade , Tabaco/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Clorofila/metabolismo , Genótipo , Malondialdeído/metabolismo , Peroxidase/metabolismo , Fotossíntese/efeitos dos fármacos , Fotossíntese/genética , Superóxido Dismutase/metabolismo , Tabaco/efeitos dos fármacos , Tabaco/genética
10.
J Chem Ecol ; 45(4): 371-377, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30880353

RESUMO

The common grass yellow Eurema mandarina (Lepidoptera: Pieridae) uses the silk tree Albizia julibrissin (Fabaceae) as a primary host in Japan. We previously reported that D-pinitol, a cyclitol found in fresh leaves of A. julibrissin, solely elicits moderate oviposition responses from females. However, the aqueous neutral/amphoteric fraction of the fresh leaf extract containing D-pinitol weakly induces oviposition. Moreover, the aqueous neutral/amphoteric/basic fraction was significantly more active than the neutral/amphoteric fraction in eliciting responses, indicating that some basic compounds are involved in stimulating oviposition. High-resolution mass spectrometry and proton nuclear magnetic resonance measurements revealed that the aqueous basic faction contains N,N,N-trimethylglycine (trivial name: glycine betaine) in alkali metal salt form. The average concentration of this quaternary ammonium compound in fresh leaves was estimated to be 0.012% w/w in high performance liquid chromatography analyses. The authentic N,N,N-trimethylglycine induced oviposition at concentrations greater than 0.001% (w/v) and slightly enhanced female responses to the aqueous neutral fraction and authentic D-pinitol. However, its analogues, N,N-dimethylglycine, N-methylglycine, and glycine as well as its precursor choline were inactive. These results demonstrate that N,N,N-trimethylglycine, together with D-pinitol, serves as an stimulant of E. mandarina for oviposition on the leaves of A. julibrissin.


Assuntos
Albizzia/química , Betaína/farmacologia , Lepidópteros/fisiologia , Oviposição/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sarcosina/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Feminino , Folhas de Planta/química , Espectroscopia de Prótons por Ressonância Magnética , Sarcosina/análogos & derivados , Espectrometria de Massas por Ionização por Electrospray
11.
Cell Stress Chaperones ; 24(2): 453-460, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30805833

RESUMO

Heat stress is one of the wide varieties of factors which cause oxidative stress in vivo; elevated temperature can lead to oxidative stress of dairy cows that affects milk production. The aim of this study was to determine the capacity of the betaine to act as an antioxidant against oxidative stress induced by heat exposure and apoptosis in mammary epithelial cells (mammary alveolar cells, MAC-T). The MAC-T were divided into four treatment groups: control (37 °C), heat stress (HS, 42 °C), betaine (37 °C), and HS + betaine. MAC-T under heat stress (HS) showed increased ROS accumulation, malondialdehyde (MDA) content, superoxide dismutase (SOD) concentration, and catalase (CAT) activity. During heat stress, betaine decreased the mRNA expression level of HSP70 and HSP27 in MAC-T. Bax/Bcl-2 ratio and caspase-3, the markers of apoptosis, were also elevated in MAC-T under heat stress. The markers of oxidative stress Nrf-2/HO-1 genes were also elevated in MAC-T under heat stress. Pretreatment of betaine reversed the heat-induced depletion in total antioxidant status, ROS accumulation, and SOD and CAT contents in MAC-T. Bax/Bcl-2 ratio and Nrf-2/HO-1 expression of heat-exposed MAC-T were also reduced with betaine supplementation. In conclusion, betaine alleviated oxidative stress and apoptosis of MAC-T by inhibiting ROS accumulation.


Assuntos
Apoptose/efeitos dos fármacos , Betaína/farmacologia , Resposta ao Choque Térmico/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspase 3/metabolismo , Catalase/metabolismo , Bovinos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Proteínas de Choque Térmico HSP72/metabolismo , Heme Oxigenase-1/metabolismo , Malondialdeído/metabolismo , Glândulas Mamárias Animais/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
12.
Mol Genet Genomic Med ; 7(4): e00579, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30811871

RESUMO

BACKGROUND: Myocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well-tolerated compound exhibiting beneficial antioxidant and anti-inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline-induced myocardial infarction in rats. METHODS: Fifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light-dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF-α and creatinine level were measured via ELISA test and colorimetric methods, respectively. RESULTS: The results of our study indicate that isoproterenol-induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF-α level significantly. CONCLUSION: According to our results, betaine has protective effects on isoprenaline-induced renal failure via a decrease in TNF-α level and nitric oxide synthase.


Assuntos
Betaína/uso terapêutico , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Animais , Betaína/farmacologia , Cardiotônicos/farmacologia , Isoproterenol/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo
13.
Eur J Pharmacol ; 847: 72-82, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30689994

RESUMO

Defect in one-carbon metabolism is one of the multiple underlying pathological pathways contributing to NAFLD pathogenesis. Hence, our study was designed to examine whether different one-carbon donors; betaine, choline, and folic acid would possess beneficial effects in NAFLD treatment. Rats were fed with high fat diet and NAFLD rats were orally treated with different doses of betaine or choline or folic acid for 28 days. All used one-carbon donors had dose-dependent ameliorating effects on NAFLD as they succeeded to reduce body and relative liver weights, serum lipids and liver enzymes. These were accompanied by decreasing hepatic fat accumulation and amending hepatic histological structure. They also improved serum and hepatic redox systems (total glutathione (tGSH), reduced GSH, oxidized GSSG, and GSH/GSSG ratio), hepatic S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) ratio and increased hepatic global DNA methylation. There were some discrepancies in the dose and the extent of their effect, where folic acid showed the most prominent effects that could be mediated through the significant surge in hepatic SAM/SAH ratio and better efficient correction of one-carbon metabolism than the other donors. Thus, one-carbon donors can be strongly considered in NAFLD management and might influence the whole therapeutic approaches of fatty liver diseases.


Assuntos
Carbono/farmacologia , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Betaína/farmacologia , Colina/farmacologia , Metilação de DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Ácido Fólico/farmacologia , Glutationa/metabolismo , Homocisteína/metabolismo , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos , Ratos Wistar , S-Adenosilmetionina/metabolismo
14.
Eur J Pharmacol ; 848: 39-48, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30689995

RESUMO

We examined the effects of betaine, an endogenous and dietary methyl donor essential for the methionine-homocysteine cycle, on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet (MCD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice received standard chow (control), standard chow and betaine (1.5% w/v in drinking water), MCD, or MCD and betaine. After six weeks, serum and liver samples were collected for analysis. Betaine reduced MCD-induced increase in liver transaminases and inflammatory infiltration, as well as hepatosteatosis and serum levels of low-density lipoprotein, while it increased that of high-density lipoprotein. MCD-induced hepatic production of reactive oxygen and nitrogen species was significantly reduced by betaine, which also improved liver antioxidative defense by increasing glutathione content and superoxide-dismutase, catalase, glutathione peroxidase, and paraoxonase activity. Betaine reduced the liver expression of proinflammatory cytokines tumor necrosis factor and interleukin-6, as well as that of proapoptotic mediator Bax, while increasing the levels of anti-inflammatory cytokine interleukin-10 and antiapoptotic Bcl-2 in MCD-fed mice. In addition, betaine increased the expression of autophagy activators beclin 1, autophagy-related (Atg)4 and Atg5, as well as the presence of autophagic vesicles and degradation of autophagic target sequestosome 1/p62 in the liver of NAFLD mice. The observed effects of betaine coincided with the increase in the hepatic phosphorylation of mammalian target of rapamycin (mTOR) and its activator Akt. In conclusion, the beneficial effect of betaine in MCD-induced NAFLD is associated with the reduction of liver oxidative stress, inflammation, and apoptosis, and the increase in cytoprotective Akt/mTOR signaling and autophagy.


Assuntos
Betaína/uso terapêutico , Deficiência de Colina/metabolismo , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Betaína/farmacologia , Deficiência de Colina/complicações , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
15.
Molecules ; 24(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669620

RESUMO

Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.


Assuntos
Betaína/farmacologia , Lipopolissacarídeos/imunologia , Microglia/efeitos dos fármacos , Microglia/fisiologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Biomarcadores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Óxido Nítrico , Fenótipo
16.
J Agric Food Chem ; 67(6): 1702-1710, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30661355

RESUMO

δ-Valerobetaine (δVB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary Nε- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of δVB is poorly known. Here, the antioxidant and anti-inflammatory potential of buffalo milk δVB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that δVB (0.5 mM) ameliorated the HG cytotoxicity (0.57 ± 0.02 vs 0.41 ± 0.018 O.D. ( P < 0.01). Interestingly, buffalo milk extracts enriched with δVB showed improved significant efficacy in decreasing reactive oxygen species, lipid peroxidation, and cytokine release during HG treatment compared to milk extracts alone ( P < 0.05). It is noteworthy that δVB reduced the HG-activated inflammatory signal by modulating SIRT1 (0.96 ± 0.05 vs 0.85 ± 0.04 AU), SIRT6 (0.82 ± 0.04 vs 0.61 ± 0.03 AU), and NF-κB (0.85 ± 0.03 vs 1.23 ± 0.03 AU) ( P < 0.05). On the whole, our data show the first evidence of δVB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Betaína/farmacologia , Leite/química , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Betaína/química , Búfalos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo
17.
Colloids Surf B Biointerfaces ; 176: 106-114, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597407

RESUMO

Cryopreservation can extend the storage time of red blood cells (RBCs) for even decades, offering a promising solution to blood waste and shortage caused by routinely used hypothermic preservation method (˜42 days). Currently, organic solvents such as glycerol or dimethyl sulfoxide are the state-of-the-art cryoprotectants (CPAs). However, severe RBC hemolysis induced by solvent CPA removal has raised serious concerns, which has been the bottleneck problem for RBC cryopreservation. Here, inspired by freezing-tolerant plants, we reported a natural zwitterionic betaine-based approach for effective RBC cryopreservation without the need of any organic solvent. Using a time-saving ultrarapid freezing protocol, about 80% of post-thaw RBC integrity rate could be achieved. Most importantly, RBC integrity was not affected during betaine removal, indicating its hemocompatibility. Mechanistically, we presented that betaine could inhibit ice formation and recrystallization during freeze-thaw cycle to protect cells from ice injury; moreover, betaine probably could be promptly taken up and released by cells to prevent them from osmotic injury. This approach provides an attractive solution for long-distance/long-term RBC transport/storage, and may benefit current cryopreservation technologies to support the lifesaving RBC transfusion.


Assuntos
Betaína/farmacologia , Crioprotetores/farmacologia , Congelamento , Plantas/efeitos dos fármacos , Animais , Varredura Diferencial de Calorimetria , Eritrócitos/efeitos dos fármacos , Ovinos , Cloreto de Sódio/farmacologia
18.
Food Funct ; 10(1): 216-223, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30534761

RESUMO

The liver plays a critical role in lipid metabolism. Hepatic dysfunction is not only the direct cause of fatty liver disease, but the main risk factor for obesity, diabetes, and other metabolic diseases. So far, therapeutic strategies against fatty liver disease are very limited. Betaine is a methyl donor. Current studies reported that the intake of betaine decreases body fat and is beneficial for treatment of fatty liver disease and metabolic syndrome. However, the underlying mechanisms remain largely unknown. In this study, to investigate the role of betaine on hepatic lipid metabolism and explore the underlying mechanism, HepG2 cells were cultured with fatty acids and betaine. The data indicated that betaine inhibited hepatic fat accumulation and promoted mitochondrial content and activity, suggesting that betaine is involved in the regulation of lipid and energy metabolism. Gene expression analysis implied that betaine inhibits fatty acid synthesis, but stimulates fatty acid oxidation and lipid secretion. Further, to study the mechanism of betaine, FTO (RNA demethylase) and its mutant (loss of demethylase activity) were used. The results showed that FTO blocked the ability of betaine to regulate lipid metabolism and mitochondrial content, but the FTO mutant had no effect, suggesting that betaine influences RNA methylation. This work links betaine administration with mitochondrial activity and RNA methylation, and provides a potential target for the development of new therapeutic strategies for the treatment of fatty liver disease.


Assuntos
Betaína/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias/efeitos dos fármacos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Ácidos Graxos/metabolismo , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Mitocôndrias/metabolismo
19.
Food Chem ; 272: 530-538, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30309578

RESUMO

Glycine betaine (GB) treatment is useful to reduce chilling injury (CI) of several kinds of fruits including peach. However, the regulatory mechanism remains unknown. In this study, peach fruit was treated with 10 mmol L-1 GB solution for 10 min. The effects of GB treatment on CI, phenolic and soluble sugar metabolism were investigated in this study. Moreover, phenylpropanoid and soluble sugar content, and enzyme activities associated with phenolic and sugar metabolisms were also measured. The results showed that GB reduced CI and maintained high levels of total phenolic and flavonoid content. The activities of phenylpropanoid metabolism-related enzymes were significantly enhanced by GB. Higher content of sucrose and lower contents of fructose and glucose were observed in GB-treated fruits. Therefore, our results showed that GB could enhance chilling tolerance of peach through regulating phenolic and sugar metabolisms, and maintaining high levels of individual phenolic and sucrose content.


Assuntos
Betaína/farmacologia , Fenóis/metabolismo , Prunus persica/metabolismo , Açúcares/metabolismo , Cromatografia Líquida de Alta Pressão , Temperatura Baixa , Frutose/metabolismo , Frutas/efeitos dos fármacos , Frutas/metabolismo , Glucose/metabolismo , Fenóis/análise , Fenilalanina Amônia-Liase/metabolismo , Prunus persica/efeitos dos fármacos
20.
Langmuir ; 35(5): 1631-1641, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30558419

RESUMO

Poly(carboxybetaine) (pCB) hydrogels do not elicit a foreign body response due to their low-fouling properties, making them ideal implantable materials for in vivo drug and cell delivery. Current reported pCB hydrogels are cross-linked using cytotoxic UV-initiated radical polymerization limiting clinical and in vivo translation. For clinical translation, we require in situ and biorthogonal cross-linking of pCB hydrogels that are both low-fouling and low-swelling to limit nonspecific interactions and minimize tissue damage, respectively. To this end, we synthesized carboxybetaine (CB) random copolymers (molecular weight (MW): ∼7-33 kDa; D: 1.1-1.36) containing azide (pCB-azide) or strained alkyne (Dibenzocyclooctyne (DBCO); pCB-DBCO) that rapidly cross-link upon mixing. Unlike CB homopolymers and other CB copolymers studied, high DBCO content pCB-DBCO30 (30% DBCO mole fraction) is thermoresponsive with a upper critical solution temperature (UCST; cloud point of ∼20 °C at 50 g/L) in water due to electrostatic associations. Due to the antipolyelectrolyte effect, pCB-DBCO30 is salt-responsive and is soluble even at low temperatures in 5 M NaCl, which prevents zwitterion electrostatic associations. pCB-azide and pCB-DBCO with 0.05 to 0.16 cross-linker mole fractions rapidly formed 10 wt % hydrogels upon mixing that were low-swelling (increase of ∼10% in wet weight) while remaining low-fouling to proteins (∼10-20 µg cm-2) and cells, making them suitable for in vivo applications. pCB-X31 hydrogels composed of pCB-azide32 and pCB-DBCO30 formed opaque gels in water and physiological conditions that shrunk to ∼70% of their original wet weight due to pCB-DBCO30's greater hydrophobicity and interchain electrostatic interactions, which promotes nonspecific protein adsorption (∼35 µg cm-2) and cell binding. Once formed, the electrostatic interactions in pCB-X31 hydrogels are not fully reversible with heat or salt. Although, pCB-X31 hydrogels are transparent when initially prepared in 5 M NaCl. This is the first demonstration of a thermo- and salt-responsive CB copolymer that can tune hydrogel protein and cell fouling properties.


Assuntos
Betaína/análogos & derivados , Hidrogéis/química , Polímeros/química , Animais , Betaína/metabolismo , Betaína/farmacologia , Incrustação Biológica/prevenção & controle , Bovinos , Adesão Celular/efeitos dos fármacos , Módulo de Elasticidade , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Células NIH 3T3 , Polímeros/metabolismo , Polímeros/farmacologia , Ligação Proteica , Soroalbumina Bovina/metabolismo , Eletricidade Estática
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