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1.
Braz. j. biol ; 84: e250936, 2024. graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1345557

ABSTRACT

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.


Subject(s)
Animals , Male , Rats , Burns/drug therapy , Glutamine , Rats, Wistar , Dipeptides , Disease Models, Animal , Amino Acids
2.
Rev. bras. ciênc. vet ; 28(2): 69-74, abr./jun. 2021. il.
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1366839

ABSTRACT

Este estudo teve por objetivo avaliar os efeitos da nutrição parenteral total ou enteral, associadas ou não à glutamina, sobre a motilidade gastrintestinal em equinos submetidos à inanição e realimentação. Foram utilizados 16 equinos adultos hígidos, sem raça definida, de ambos os sexos, quatro machos e 12 fêmeas, com idade variando entre quatro e 14 anos e peso corporal médio de 248,40 + 2,28 kg, divididos em quatro grupos, quatro animais por grupo: Grupo I (ENTGL): fluidoterapia enteral com eletrólitos associada a glutamina; Grupo II (PARGL): Nutrição parenteral total (NPT) associada a glutamina; Grupo III (ENTFL): fluidoterapia enteral com eletrólitos; Grupo IV (PARFL): fluidoterapia parenteral. O delineamento experimental foi inteiramente ao acaso, em um esquema fatorial 4x12 (grupos x tempo de colheita), para cada fase, e suas médias comparadas pelo teste de Duncan ao nível de 5% de significância. Independente do grupo experimental ocorreu redução da motilidade gastrintestinal durante a fase de inanição, mais pronunciada nos grupos PARGL e PARFL. Uma vez restabelecida a alimentação a motilidade gastrintestinal retornou à normalidade.


This study aimed to evaluate the effects of enteral or total parenteral nutrition, associated or not with glutamine, on gastrointestinal motility in horses subjected to starvation and refeeding. 16 healthy, mixed-breed adult horses of both sexes, four geldings and 12 mares, with ages ranging from four to 14 years and an average body weight of 248.40 + 2.28 kg, were divided into four groups, four animals per group: Group I (ENTGL): enteral fluid therapy with electrolytes associated with glutamine; Group II (PARGL): total parenteral nutrition (TPN) associated with glutamine; Group III (ENTFL): enteral fluid therapy with electrolytes; Group IV (PARFL): parenteral fluid therapy. The experimental design was entirely randomized, in a 4x12 factorial scheme (groups x harvest time), for each phase, and their means compared by the Duncan test at the level of 5% significance. Regardless of the experimental group, there was a reduction in gastrointestinal motility during the starvation phase, which was more pronounced in the PARGL and PARFL groups. Once the food was restored, gastrointestinal motility returned to normal.


Subject(s)
Animals , Enteral Nutrition/veterinary , Parenteral Nutrition, Total/veterinary , Gastrointestinal Motility , Horses , Starvation/veterinary , Glutamine/therapeutic use
3.
Article in English | WPRIM | ID: wpr-922588

ABSTRACT

OBJECTIVES@#To explore the metabolite characteristics in medial prefrontal cortex (mPFC) by @*METHODS@#A total of 46 patients with the first-episode schizophrenia (FES), 49 people with clinical high risk (CHR), 61 people with genetic high risk (GHR), and 58 healthy controls (HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate (tNAA), choline-containing compounds (Cho) and myo-inositol (MI), glutamate+glutamine (Glx) in medial prefrontal cortex were measured by single-voxel @*RESULTS@#There were significant differences in Glx, tNAA, and MI concentrations among 4 groups (all @*CONCLUSIONS@#The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.


Subject(s)
Aspartic Acid , Glutamic Acid , Glutamine , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy , Schizophrenia
4.
Article in English | WPRIM | ID: wpr-922098

ABSTRACT

OBJECTIVE@#To investigate the synergistic effect of Naoxintong Capsule (NXTC, ) and Guhong Injection (GHI, ) on cerebral ischemia-reperfusion (I/R) injury.@*METHODS@#Forty-eight Sprague-Dawley rats were divided into 6 groups: control group, oxygen and glucose deprivation (OGD) group, nimodipine group (9.375 mg/kg), NXTC group (0.5 g/kg), GHI group (5 mL/kg) and NXTC+GHI group (0.5 g/kg NXTC+5 mL/kg GHI), after the onset of reperfusion and once per day for the following 7 days. Blood was collected 1 h after final administration, and the sera were collected. Cultured primary rat brain microvascular endothelial cells (rBMECs) were subjected to OGD to establish a cell injury model. Untreated rBMECs were used as blank control. The cell counting kit-8 assay was used to assess cell viability using the sera. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed using an enzyme-linked immunosorbent assay. Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry. JC-1 staining was performed to assess changes in mitochondrial membrane potential.@*RESULTS@#Statistical analysis indicated that more than 95% of the cells were rBMECs. Compared with the OGD group, the cellular morphology of the all drug delivery groups improved. In particular, the combined drug group had the most significant effect. Compared with the OGD group, all drug intervention groups induced a decrease in the apoptotic rate of rBMECs, increased the SOD levels, and decreased the MDA levels (all P<0.01). Compared with the mono-therapy groups, the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs (P<0.01). All drug intervention groups showed different degrees of increase in membrane potential, and the NXTC+GHI group was higher than the NXTC or GHI group (P<0.01).@*CONCLUSION@#The combinationa application of NXTC and GHI on cerebral I/R injury clearly resulted in protective benefits.


Subject(s)
Animals , Apoptosis , Brain , Brain Ischemia/drug therapy , Drugs, Chinese Herbal , Endothelial Cells , Glutamine/analogs & derivatives , Plant Extracts , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy
5.
Article in English | WPRIM | ID: wpr-888702

ABSTRACT

Oral immunosuppression caused by smoking creates a microenvironment to promote the occurrence and development of oral mucosa precancerous lesions. This study aimed to investigate the role of metabolism and macrophage polarization in cigarette-promoting oral leukoplakia. The effects of cigarette smoke extract (CSE) on macrophage polarization and metabolism were studied in vivo and in vitro. The polarity of macrophages was detected by flow cytometric analysis and qPCR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform a metabolomic analysis of Raw cells stimulated with CSE. Immunofluorescence and flow cytometry were used to detect the polarity of macrophages in the condition of glutamine abundance and deficiency. Cell Counting Kit-8 (CCK-8), wound-healing assay, and Annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) double-staining flow cytometry were applied to detect the growth and transferability and apoptosis of Leuk-1 cells in the supernatant of Raw cells which were stimulated with CSE, glutamine abundance and deficiency. Hyperkeratosis and dysplasia of the epithelium were evident in smoking mice. M2 macrophages increased under CSE stimulation in vivo and in vitro. In total, 162 types of metabolites were detected in the CSE group. The metabolites of nicotine, glutamate, arachidic acid, and arginine changed significantly. The significant enrichment pathways were also selected, including nicotine addiction, glutamine and glutamate metabolism, and arginine biosynthesis. The results also showed that the supernatant of Raw cells stimulated by CSE could induce excessive proliferation of Leuk-1 and inhibit apoptosis. Glutamine abundance can facilitate this process. Cigarette smoke promotes oral leukoplakia via regulating glutamine metabolism and macrophage M2 polarization.


Subject(s)
Animals , Glutamine , Leukoplakia, Oral , Macrophages , Mice , Smoking , Tumor Microenvironment
6.
Article in Chinese | WPRIM | ID: wpr-880133

ABSTRACT

OBJECTIVE@#To investigate the effect of V-9302 (an antagonist of transmembrane glutamine flux) on the proliferation and apoptosis of acute myeloid leukemia cells HL-60 and KG-1.@*METHODS@#HL-60 and KG-1 cells at logarithmic phase were treated by different concentrations of V-9302. CCK-8 assay was used to detect the proliferation of the cells. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of HL-60 and KG-1 cells. The expressions of BAX, BCL-2 and Caspase3 were detected by RT-qPCR and Western blot.@*RESULTS@#V-9302 could significantly inhibit the growth of HL-60 and KG-1 cells. The concentration of V-9302 at 10, 20 μmol/L could significantly promote the apoptosis of HL-60 and KG-1 cells(P<0.05). The results of apoptosis related gene detection showed that when V-9302 was applied to HL-60 and KG-1 cell lines at 10 and 20 μmol/L, the expression levels of Pro-apoptotic protein genes BAX and Caspase3 in HL-60 and KG-1 were significantly higher than those in control group (P<0.05), while the expression level of anti-apoptotic protein gene BCL-2 was significantly lower than that in the control group (P<0.05). The results of Western blot were basically consistent with that of RT-qPCR.@*CONCLUSION@#Competitive antagonist of transmembrane glutamine flux V-9302 can significantly promote the apoptosis of acute myeloid leukemia cell lines HL-60 and KG-1.


Subject(s)
Apoptosis , Cell Proliferation , Glutamine , HL-60 Cells , Humans , Leukemia, Myeloid, Acute
7.
Article in English | WPRIM | ID: wpr-879944

ABSTRACT

The metabolic reprogramming of tumor cells is characterized by increased uptake of various nutrients including glutamine. Glutamine metabolism provides the required substances for glycolysis and oxidative phosphorylation and affects the homeostasis of carbohydrate,fat and protein metabolism to induce the chemoresistance of tumor cells. Combination of chemotherapeutic agents with inhibitors specific to different components of glutamine metabolic pathway has obtained favorable clinical results on various tumors. Glutamine metabolic pathway plays a role in drug resistance of tumor cells in various ways. Firstly,the dynamic change of glutamine transporters can directly affect intracellular glutamine content thereby causing drug resistance; secondly,tumor stromal cells including adipocyte,fibroblast and metabolite from tumor microenvironment would give rise to immune-mediated drug resistance; thirdly,the expression and activity of key enzymes in glutamine metabolism also has a critical role in drug resistance of tumors. This article reviews the effects of glutamine metabolic pathway in the development of tumor chemoresistance,in terms of transporters,tumor microenvironment and metabolic enzymes,to provide insight for improving the therapeutic efficacy for drug-resistant tumors.


Subject(s)
Cell Line, Tumor , Drug Resistance, Neoplasm , Glutamine/metabolism , Glycolysis , Humans , Neoplasms/drug therapy , Oxidative Phosphorylation , Tumor Microenvironment
8.
Arq. bras. med. vet. zootec. (Online) ; 72(5): 1789-1796, Sept.-Oct. 2020. tab
Article in English | LILACS, VETINDEX | ID: biblio-1131541

ABSTRACT

This study aimed to evaluate glutamine supplementation effects on variables of growth performance, body composition, intestinal morphology and enzymatic aspects of juvenile Arapaima gigas. Research was conducted at the Fish Nutrition and Feeding Laboratory, where 60 examples of pirarucu (initial average weight of 82.12g) were distributed over 15 polyethylene tanks (310L), in a completely randomized design, with five treatments and three repetitions (four fish per experimental unit). Experimental diets were prepared containing five inclusion levels of the amino acid glutamine (0.0, 0.5, 1.0, 1.5 and 2.0%), supplied three times a day for 45 days. Quadratic effect was observed for the variables of growth performance, weight gain, food consumption, food conversion, and specific growth and protein efficiency rates. A significant effect was observed on intestinal villi at the height of the anterior portion and on activity of the enzyme's alkaline proteases, lipase, amylase and aspartate aminotransferase. However, glutamine supplementation had no significant effect on survival rate. Inclusion of 1.02% of glutamine in the diets of juvenile pirarucu improved growth performance and influenced intestinal villi height and activity of important digestive enzymes, favoring nutrient digestion and absorption.(AU)


Objetivou-se avaliar os efeitos da suplementação com glutamina sobre variáveis de desempenho produtivo, composição corporal, morfologia do intestino e aspectos enzimáticos de juvenis de Arapaima gigas. O experimento foi conduzido no Laboratório de Nutrição e Alimentação de Peixes, onde 60 exemplares de pirarucu (peso médio inicial de 82,12g) foram distribuídos em 15 tanques de polietileno (310L), em delineamento inteiramente ao acaso, com cinco tratamentos e três repetições (quatro peixes por unidade experimental). As dietas experimentais foram confeccionadas contendo cinco níveis de inclusão do aminoácido glutamina (0,0; 0,5; 1,0; 1,5 e 2,0%), fornecidas três vezes ao dia, ao longo de 45 dias. Foi observado efeito quadrático para variáveis de desempenho produtivo: ganho de peso, consumo alimentar, conversão alimentar, taxa de crescimento específico e taxa de eficiência proteica. Observou-se ainda efeito significativo sobre a altura das vilosidades da porção anterior do intestino e a atividade das enzimas: proteases alcalinas, lipase, amilase e aspartato aminotransferase. Entretanto, a suplementação com glutamina não influenciou significativamente a sobrevivência dos animais. A adição de 1,02% de glutamina nas dietas para juvenis de pirarucu melhorou o desempenho produtivo e influenciou a altura das vilosidades intestinais e a atividade de enzimas digestivas importantes, favorecendo a digestão e a absorção de nutrientes.(AU)


Subject(s)
Animals , Fishes/metabolism , Amino Acids/administration & dosage , Glutamine/administration & dosage , Animal Feed/analysis
9.
São Paulo; s.n; s.n; 2020. 27 p.
Thesis in English | LILACS | ID: biblio-1361417

ABSTRACT

Fatigue is defined as the inability to maintain muscle power and strength, impairing performance. Nutritional interventions have been used to delay this phenomenon, such as glutamine and alanine supplementation. These amino acids might attenuate several causes of fatigue, since they are important energy substrates, transport ammonia avoiding the accumulation of this toxic metabolite and attenuate muscle damage and oxidative stress. Thus, the aim of this study was to evaluate the effects of glutamine and alanine supplementation on central and muscle fatigue parameters of rats submitted to resistance training (RT). Forty adult Wistar rats (60 days) were distributed into five groups: SED (sedentary, receiving water), CON (trained, receiving water), ALA, G+A and DIP (trained and supplemented with alanine, glutamine and alanine in their free form, and Lalanyl-L-glutamine, respectively). Trained groups underwent a ladder-climbing exercise, with progressive loads, for eight weeks. Supplements were diluted in water to a 4% concentration and offered ad libitum during the last 21 days of experiment. RT increased plasma glucose, the muscle concentrations of ammonia and glutathione (GSH) and the muscle damage parameters - plasma creatine kinase (CK) and lactate dehydrogenase (LDH), whereas decreased muscle glycogen. G+A supplementation prevented the increase of muscle ammonia by RT, while ALA and G+A administration reduced plasma CK and LDH, and DIP supplementation increased the muscle content of glycogen and LDH. Contrary to expectations, DIP administration increased central fatigue parameters, such as plasma concentration of free fatty acids (FFA), hypothalamic content of serotonin and serotonin/dopamine ratio. Despite these results, there was no difference between groups in the maximum carrying capacity (MCC) tests. In conclusion, supplementation with glutamine and alanine improves some fatigue parameters, but does not affect physical performance of rats submitted to RT


O termo fadiga é definido como a incapacidade de manutenção da força e da potência musculares, prejudicando a performance. Intervenções nutricionais têm sido utilizadas para retardar este fenômeno, como a suplementação com glutamina e alanina. Estes aminoácidos poderiam atenuar diversas causas de fadiga, pois são importantes substratos energéticos, carreiam amônia evitando o acúmulo deste metabólito tóxico e atenuam a lesão muscular e o estresse oxidativo. Logo, o objetivo deste estudo foi avaliar os efeitos da suplementação com glutamina e alanina sobre parâmetros de fadiga central e muscular em ratos submetidos ao treinamento resistido (TR). Foram utilizados 40 ratos Wistar adultos (60 dias de idade), distribuídos nos grupos: SED (não treinados, recebendo água), CON (treinados, recebendo água), ALA, G+A e DIP (treinados e suplementados com alanina, glutamina e alanina livres, e L-alanil-L-glutamina, respectivamente). Os grupos treinados realizaram um exercício de escalada em escada, com aumento progressivo de carga, durante oito semanas. A suplementação foi diluída a 4% em água e ofertada via oral, ad libitum, durante os últimos 21 dias de experimento. O TR aumentou a glicemia, as concentrações musculares de amônia e de glutationa (GSH) e os parâmetros de lesão muscular - creatina quinase (CK) e lactato desidrogenase (LDH) no plasma, enquanto reduziu o glicogênio no músculo. A suplementação com G+A preveniu o aumento de amônia muscular promovido pelo TR, enquanto a administração de ALA e G+A reduziu as concentrações de CK e LDH no plasma, e a suplementação com DIP aumentou o conteúdo muscular de glicogênio e de LDH. Ao contrário do esperado, a administração de DIP aumentou parâmetros de fadiga central, como as concentrações plasmáticas de ácidos graxos livres, o conteúdo hipotalâmico de serotonina e a razão serotonina/dopamina. Apesar disso, não houve diferença entre os grupos nos testes de carga máxima. Em conclusão, a suplementação com glutamina e alanina melhora alguns parâmetros de fadiga, mas não afeta o desempenho físico em ratos submetidos ao TR


Subject(s)
Animals , Male , Female , Rats , Dietary Supplements/classification , Alanine/antagonists & inhibitors , Fatigue/classification , Glutamine/antagonists & inhibitors , Blood Glucose/immunology , Water/pharmacology , Exercise/physiology , Resistance Training/methods , Physical Functional Performance
10.
Geriatr., Gerontol. Aging (Impr.) ; 13(1): 28-35, jan-mar.2019. tab
Article in Portuguese | LILACS | ID: biblio-1005555

ABSTRACT

OBJETIVO: Comparar resultados da suplementação com prebiótico, probiótico e simbiótico para o controle da diarreia em pacientes idosos recebendo terapia nutricional enteral durante o internamento em um hospital escola de Curitiba, Paraná. MÉTODOS: O estudo foi retrospectivo, por análise de prontuários correspondentes aos atendimentos realizados entre 2014 e 2018. RESULTADOS: Obteve-se um total de 75 pacientes. O tempo de ocorrência de diarreia variou de 1 a 16 dias, sendo a média de 2,69 dias após a instituição de terapêutica para restabelecimento da microbiota intestinal. Quanto às terapias instituídas, foram encontradas oito possíveis prescrições de suplementos isolados e/ou combinados, como primeira escolha. Dos pacientes analisados, 52% trocaram de suplementação ao longo da ocorrência da diarreia; alguns chegando a utilizar até cinco diferentes produtos. Dos 48% de pacientes que utilizaram um único produto/combinação do início ao fim da diarreia, de modo geral iniciaram com uma dose maior e foram diminuindo ao longo do tempo, sendo que os que começaram com uma dose menor tiveram que aumentá-la para interromper a diarreia. Além disso, houve significância estatística quando comparado o tempo de diarreia entre pacientes que receberam um único produto/combinação e os que fizeram trocas de suplemento ao longo do tratamento. CONCLUSÃO: Estabelecer uma prescrição única, seja de produtos isolados ou combinados, e permanecer com ela, além de iniciar com uma dose maior, parece mais efetivo no controle da diarreia em idosos hospitalizados, reforçando a importância de se estabelecer um protocolo para prescrição.


OBJECTIVE: To compare results of prebiotic, probiotic and synbiotic supplementation for the control of diarrhea in older patients receiving enteral nutritional therapy during hospitalization at a school hospital in Curitiba, state of Paraná. METHODS: The study was retrospective, by analysis of medical records corresponding to the visits performed between 2014 and 2018. RESULTS: A total of 75 patients were analyzed. The time of occurrence of diarrhea ranged from 1 to 16 days, with a mean of 2.69 days after the onset of therapy for reestablishment of the intestinal microbiota. As for the therapies introduced, 8 possible prescriptions of isolated and / or combined supplements were found as the first choice. Of the patients analyzed, 52% switched from supplementation during the occurrence of diarrhea; some using up to 5 different products. Of the 48% of patients who used a single product / combination from the beginning to the end of diarrhea, they generally started with a higher dose and decreased over time, with those starting at a lower dose having to increase it to stop diarrhea. In addition, there was statistical significance when comparing the time of diarrhea between patients who received a single product / combination and those who did supplemental exchanges throughout the treatment. CONCLUSION: Establishing a single prescription, whether of isolated or combined products and sticking to it, besides starting with a higher dose, seems more effective in controlling diarrhea in hospitalized geriatric patients, reinforcing the importance of establishing a protocol for prescription.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Enteral Nutrition/statistics & numerical data , Dietary Supplements , Diarrhea/diet therapy , Diarrhea/rehabilitation , Hospitalization , Health of the Elderly , Probiotics/administration & dosage , Synbiotics/administration & dosage , Glutamine/administration & dosage
11.
Rev. bras. psiquiatr ; 41(2): 168-178, Mar.-Apr. 2019. tab
Article in English | LILACS | ID: biblio-990820

ABSTRACT

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.


Subject(s)
Humans , Animals , Anxiety Disorders/drug therapy , Acetylcysteine/pharmacology , Anti-Anxiety Agents/pharmacology , Fatty Acids, Omega-3/pharmacology , Hypnotics and Sedatives/pharmacology , Acetamides/pharmacology , Neuroimmunomodulation/drug effects , Oxidative Stress/drug effects , Disease Models, Animal , Glutamine/drug effects
12.
Article in English | WPRIM | ID: wpr-777640

ABSTRACT

BACKGROUND@#Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP)-induced Parkinson's disease cell model.@*METHODS@#MPP was used to induce PD models in PC12 cells and classified into control, M0 (MPP), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR.@*RESULTS@#We showed that glutamine suppressed cytotoxicity induced by MPP in PC12 cells. MPP decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1.@*CONCLUSION@#These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.


Subject(s)
1-Methyl-4-phenylpyridinium , Analysis of Variance , Animals , Cell Culture Techniques , Disease Models, Animal , Glutamine , Pharmacology , Oxidative Stress , Parkinson Disease , Phosphatidylinositol 3-Kinases , Metabolism , Protective Agents , Pharmacology , Proto-Oncogene Proteins c-akt , Metabolism , Rats
13.
Article in Chinese | WPRIM | ID: wpr-776543

ABSTRACT

OBJECTIVE@#To investigate the effects of aerobic exercise and glutamine (Gln) on anti-oxidative stress and inflammatory factors in type 2 diabetes mellitus (T2MD) rats.@*METHODS@#Diabetic rat model was induced by streptozotocin (STZ). Fifty 6-week old male SD rats were randomly divided into 5 groups (n=10), including quiet control group (N), diabetes control group (D), diabetic aerobic exercise group (DE), diabetic glutamine group (DG) and diabetic aerobic exercise glutamine group (DEG). After 6 weeks, the related indicators of glucose and lipid metabolism, anti-oxidative stress and inflammatory factors in diabetic rats were detected, and the possible mechanism affecting inflammatory response were explored.@*RESULTS@#Compared with group N, the levels of serum malondialdehyde(MDA), blood glucose, total cholesterol(TC), triglyceride(TG), insulin, leptin and tumor necrosis factor-α(TNF-α) in group D were increased significantly (P<0.01). Compared with group D, serum levels of MDA, blood glucose, TC, TG, insulin, leptin and TNF-α in three intervention groups were decreased significantly, while the levels of SOD, GSH-Px and adiponectin were increased, and the combined effect was more obvious (P<0.01).@*CONCLUSION@#Both aerobic exercise and Gln can relieve the glucose and lipid metabolism and disturbance, oxidative stress injury and inflammation in diabetic rats.


Subject(s)
Animals , Blood Glucose , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Therapeutics , Glutamine , Pharmacology , Leptin , Blood , Lipid Metabolism , Lipids , Blood , Male , Malondialdehyde , Blood , Oxidative Stress , Physical Conditioning, Animal , Random Allocation , Rats , Rats, Sprague-Dawley
14.
Biol. Res ; 52: 15, 2019. graf
Article in English | LILACS | ID: biblio-1011417

ABSTRACT

BACKGROUND: Tumourigenic cells modify metabolic pathways In order to facilitate increased proliferation and cell survival resulting in glucose-and glutamine addiction. Previous research indicated that glutamine deprivation resulted in potential differential activity targeting tumourigenic cells more prominently. This is ascribed to tumourigenic cells utilising increased glutamine quantities for enhanced glycolysis-and glutaminolysis. In this study, the effects exerted by glutamine deprivation on reactive oxygen species (ROS) production, mitochondrial membrane potential, cell proliferation and cell death in breast tumourigenic cell lines (MCF-7, MDA-MB-231, BT-20) and a non-tumourigenic breast cell line (MCF-10A) were investigated. RESULTS: Spectrophotometry demonstrated that glutamine deprivation resulted in decreased cell growth in a time-dependent manner. MCF-7 cell growth was decreased to 61% after 96 h of glutamine deprivation; MDA-MB-231 cell growth was decreased to 78% cell growth after 96 h of glutamine deprivation, MCF-10A cell growth was decreased 89% after 96 h of glutamine deprivation and BT-20 cell growth decreased to 86% after 24 h of glutamine deprivation and remained unchanged until 96 h of glutamine deprivation. Glutamine deprivation resulted in oxidative stress where superoxide levels were significantly elevated after 96 h in the MCF-7-and MDA-MB-231 cell lines. Time-dependent production of hydrogen peroxide was accompanied by aberrant mitochondrial membrane potential. The effects of ROS and mitochondrial membrane potential were more prominently observed in the MCF-7 cell line when compared to the MDA-MB-231-, MCF-10A- and BT-20 cell lines. Cell cycle progression revealed that glutamine deprivation resulted in a significant increase in the S-phase after 72 h of glutamine deprivation in the MCF-7 cell line. Apoptosis induction resulted in a decrease in viable cells in all cell lines following glutamine deprivation. In the MCF-7 cells, 87.61% of viable cells were present after 24 h of glutamine deprivation. CONCLUSION: This study demonstrates that glutamine deprivation resulted in decreased cell proliferation, time-dependent- and cell line-dependent ROS generation, aberrant mitochondrial membrane potential and disrupted cell cycle progression. In addition, the estrogen receptor positive MCF-7 cell line was more prominently affected. This study contributes to knowledge regarding the sensitivity of breast cancer cells and non-tumorigenic cells to glutamine deprivation.


Subject(s)
Humans , Female , Breast Neoplasms/pathology , Cell Survival , Reactive Oxygen Species/metabolism , Oxidative Stress , Cell Proliferation , Glutamine/deficiency , Spectrophotometry , Breast Neoplasms/metabolism , Apoptosis , Cell Line, Tumor , Glutamine/metabolism
15.
ABCD arq. bras. cir. dig ; 32(2): e1431, 2019. graf
Article in English | LILACS | ID: biblio-1001043

ABSTRACT

ABSTRACT Background: Sepsis is an important public health issue and is associated with high treatment costs and high mortality rates. Glutamine supplementation has proven to be beneficial to the functions of the immune system, acting beneficially in the evolution of patients in severe catabolic states. Aim: To evaluate the effect of glutamine supplementation via intraperitoneal in rats, induced sepsis, considering the following organs: intestines, liver, kidneys and lungs. Methods: Male Wistar rats subjected to sepsis by ligature and cecal puncture were divided into two groups: control C (n=6) and glutamine G (n=11), in which were administered dipeptiven 20% at a dose of 2 ml/kg/day (equivalent to 0.4g N(2)-L-alanyl-L-glutamine/kg) intraperitoneally 48 h prior to sepsis induction. After 48 h they were euthanized and intestine, liver, lung and kidney were removed for histological analysis. Results: Intestinal epithelial desquamation of the control group was more intense compared to the glutamine group (p=0.008). In the kidneys, degenerative tubular epithelial changes were less severe in the animals that received glutamine (p=0.029). Regarding to the liver, glutamine group showed lower levels of cell swelling than the control group (p=0.034). In the lung there were no results with statistical significance. Conclusion: Prior intraperitoneal supplementation with glutamine in experimental animals is able to reduce the damage to the intestinal mucosa, to the kidneys and liver's histoarchitecture.


RESUMO Racional: A sepse é importante problema de saúde pública, sendo relacionada com altos custos de tratamento e elevadas taxas de mortalidade. A suplementação de glutamina tem provado ser benéfica às funções do sistema imune, atuando em estados catabólicos graves. Objetivo: Avaliar o efeito da suplementação de glutamina via intraperitoneal em ratos induzidos à sepse. Método: Foram utilizados ratos Wistar submetidos à sepse por ligadura e punção do ceco, separados em grupo controle C (n=6) e glutamina G (n=11), aos quais foram administrados dipeptiven a 20% com dose de 2 ml/kg/dia (equivalente a 0,4 g N(2)-L-alanil-L-glutamina/kg), via intraperitoneal, 48 h antes da indução da sepse. Após 48 h todos os animais foram submetidos à eutanásia e intestino, fígado, pulmão e rim foram retirados para análise histológica. Resultados: No intestino a descamação epitelial do grupo controle foi mais intensa em comparação ao da glutamina (p=0,008). Nos rins, houve menor degeneração do epitélio tubular nos animais que receberam glutamina (p=0,029). No fígado, o grupo glutamina apresentou índices menores de tumefação celular do que o grupo controle (p=0,034). No pulmão não houve resultados com significância estatística. Conclusão: A suplementação prévia de animais experimentais com glutamina via intraperitoneal é capaz de reduzir os danos causados à mucosa intestinal, histoarquitetura dos rins e do fígado.


Subject(s)
Animals , Male , Sepsis/drug therapy , Glutamine/administration & dosage , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Sepsis/pathology , Infusions, Parenteral , Intestines/drug effects , Intestines/pathology , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Lung/drug effects , Lung/pathology
16.
Article in Chinese | WPRIM | ID: wpr-774122

ABSTRACT

OBJECTIVE@#To study the effect of glutamine-supplemented enteral nutrition in regulating the apoptosis of intestinal mucosal cells and promoting mucosal healing in young rats with inflammatory bowl disease (IBD).@*METHODS@#A total of 80 male Sprague-Dawley rats aged 4-5 weeks were randomly divided into 4 groups: blank control, IBD model, short peptide, and short peptide+glutamine (n=20 each). The IBD model was prepared by a single colon perfusion of 3-nitrobenzene sulfonic acid. At 3 days after modeling, the rats in the short peptide group were fed with short peptide formula (100 mL/kg), and those in the short peptide+glutamine group were fed with short peptide formula (100 mL/kg) and glutamine (0.5 g/kg). The course of intervention was 1 week. General conditions were observed after the experiment and their intestinal mucosal tissue was obtained. Hematoxylin-eosin staining was used to observe the pathological change of the intestinal mucosa. RT-PCR was used to measure the expression of apoptosis-regulating genes (bax and bc1-2) and apoptotic signal transduction factors (Caspase-3 and Caspase-9) in the intestinal mucosa. Western blot was used to measure the expression of insulin-like growth factor-1 (IGF-1) in the colonic mucosa.@*RESULTS@#The IBD model group had poorer general conditions than the other three groups (blank control, short peptide and short peptide+glutamine), and the short peptide+glutamine group had better general conditions than the IBD model and short peptide groups. The IBD model group had significantly higher mRNA expression of bax than the other three groups (P0.05). The short peptide group had a significantly higher level of IGF-1 than the short peptide+glutamine, blank control and IBD model groups (P<0.05).@*CONCLUSIONS@#Glutamine-supplemented enteral nutrition can effectively improve the general nutritional status of young rats with IBD, but it is not better than exclusive enteral nutrition in inhibiting the apoptosis of colonic mucosal cells and stimulating the synthesis of IGF-1 in the intestinal mucosa.


Subject(s)
Animals , Apoptosis , Enteral Nutrition , Glutamine , Intestinal Mucosa , Male , Rats , Rats, Sprague-Dawley
17.
Psychiatry Investigation ; : 745-750, 2019.
Article in English | WPRIM | ID: wpr-760906

ABSTRACT

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study evaluated the antidepressant effect of rTMS and examined how it affected N-asetyl aspartate (NAA), choline (Cho), creatine (Cr), lactate (Lac), myoinositol (mIns), glutamate (Glu), glutathione (GSH), and glutamine (Gln) metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) of MDD patients who were not receiving antidepressant medication. METHODS: In total, 18 patients (10 female, 8 male) were evaluated. Each patient underwent H magnetic resonance spectroscopy (H-MRS) before and within 3 days of completion of TMS therapy. All patients completed 20 sessions of rTMS directed at the left DLPFC over a 2-week period. The Hamilton Depression Scale (HAMD) scores of patients were calculated, and their responses to treatment were assessed within 1–3 days of completion of TMS. RESULTS: We found statistically significant differences in HAMD scores before and after rTMS. Moreover, the peak metabolite ratios of NAA/Cr, GSH/Cr, and Gln/Cr were significantly higher after rTMS compared to those before rTMS. CONCLUSION: Increased understanding of the mechanism of action of TMS will improve its application and may stimulate development of new-generation therapeutic agents.


Subject(s)
Aspartic Acid , Choline , Creatine , Depression , Depressive Disorder, Major , Female , Glutamic Acid , Glutamine , Glutathione , Humans , Inositol , Lactic Acid , Magnetic Resonance Spectroscopy , Prefrontal Cortex , Transcranial Magnetic Stimulation
18.
Experimental Neurobiology ; : 270-278, 2019.
Article in English | WPRIM | ID: wpr-739539

ABSTRACT

Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln-supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS.


Subject(s)
Amino Acid Transport System X-AG , Amino Acid Transport Systems , Animals , Astrocytes , Depression , Depressive Disorder , Diet , Glutamic Acid , Glutamine , Immobilization , Mice , Neurons , Prefrontal Cortex , Transportation
19.
Blood Research ; : 23-30, 2019.
Article in English | WPRIM | ID: wpr-739438

ABSTRACT

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients. METHODS: In this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group. RESULTS: Regarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group. CONCLUSION: Results showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.


Subject(s)
Adult , Glutamine , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Mortality , Mucositis , Multivariate Analysis , Nausea , Neutropenia , Odds Ratio , Parenteral Nutrition , Parenteral Nutrition, Total , Retrospective Studies , Seoul , Transplants , Vomiting
20.
Article in Korean | WPRIM | ID: wpr-764378

ABSTRACT

PURPOSE: To evaluate the clinical effect of intravenous glutamine administration on patients admitted to the intensive care unit in general hospitals. METHODS: Patients with more than 7 days in an intensive care unit were evaluated. The experimental group was the patients who received intravenous glutamine administration for more than 3 days. The laboratory results, intensive care unit length of stay, hospital length of stay, 30 days mortality, and hospital mortality were evaluated with a comparative group. RESULTS: The mean number of administration days of intravenous glutamine was 10.12±8.93 days, and the average daily dose was 0.33±0.10 g/kg/day. No adequate improvement in the laboratory results of glutamine-treated group was observed. The intensive care unit length of stay (21.16±15.83 vs. 16.48±11.06, P=0.007), hospital length of stay (35.94±30.75 vs. 27.34±19.09, P=0.010), 30 days mortality (20.0% vs. 10.0%, P=0.034), and hospital mortality (26.3% vs. 13.0%, P=0.001) were higher in the glutamine-treated group. CONCLUSION: The use of intravenous glutamine on intensive care unit patients did not improve the clinical effect. Further large-scale multi-center studies will be needed to assess the proper administration of intravenous glutamine on intensive care unit patients.


Subject(s)
Critical Care , Glutamine , Hospital Mortality , Hospitals, General , Humans , Intensive Care Units , Length of Stay , Mortality
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