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1.
Appl Physiol Nutr Metab ; 41(8): 842-849, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27447686

RESUMEN

In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p < 0.05). The results presented herein demonstrate that l-glutamine supplemented with l-alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.


Asunto(s)
Alanina/administración & dosificación , Glutamina/administración & dosificación , Glutatión/sangre , Proteínas de Choque Térmico HSP27/metabolismo , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal , Alanina/sangre , Animales , Creatina Quinasa/sangre , Proteínas de Unión al ADN/metabolismo , Suplementos Dietéticos , Eritrocitos/citología , Eritrocitos/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Glutamina/sangre , Disulfuro de Glutatión/sangre , Factores de Transcripción del Choque Térmico , Masculino , Mioglobina/sangre , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Transcripción/metabolismo
2.
Br J Nutr ; 116(3): 470-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27215379

RESUMEN

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1ß, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1ß, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.


Asunto(s)
Alanina/farmacología , Antiinflamatorios/farmacología , Suplementos Dietéticos , Dipéptidos/farmacología , Glutamina/farmacología , Músculo Esquelético/efectos de los fármacos , Entrenamiento de Fuerza/efectos adversos , Alanina/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Creatina Quinasa/sangre , Citocinas/sangre , Dipéptidos/uso terapéutico , Glutamina/sangre , Glutamina/metabolismo , Glutamina/uso terapéutico , Proteínas HSP70 de Choque Térmico/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , L-Lactato Deshidrogenasa/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Músculo Esquelético/metabolismo , FN-kappa B/metabolismo , Ratas Wistar
3.
Int J Sport Nutr Exerc Metab ; 25(2): 188-97, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25202991

RESUMEN

Liver L-glutamine is an important vehicle for the transport of ammonia and intermediary metabolism of amino acids between tissues, particularly under catabolic situations, such as high-intensity exercise. Hence, the aim of this study was to investigate the effects of oral supplementations with L-glutamine in its free or dipeptide forms (with L-alanine) on liver glutamine-glutathione (GSH) axis, and 70 kDa heat shock proteins (HSP70)/heat shock transcription factor 1 (HSF1) expressions. Adult male Wistar rats were 8-week trained (60 min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were daily supplemented with 1 g of L-glutamine/kg body weight per day in either l-alanyl-L-glutamine dipeptide (DIP) form or a solution containing L-glutamine and l-alanine in their free forms (GLN+ALA) or water (controls). Exercise training increased cytosolic and nuclear HSF1 and HSP70 expression, as compared with sedentary animals. However, both DIP and GLN+ALA supplements enhanced HSF1 expression (in both cytosolic and nuclear fractions) in relation to exercised controls. Interestingly, HSF1 rises were not followed by enhanced HSP70 expression. DIP and GLN+ALA supplements increased plasma glutamine concentrations (by 62% and 59%, respectively) and glutamine to glutamate plasma ratio in relation to trained controls. This was in parallel with a decrease in plasma ammonium levels. Supplementations increased liver GSH (by 90%), attenuating the glutathione disulfide (GSSG) to GSH ratio, suggesting a redox state protection. In conclusion, oral administration with DIP and GLN+ALA supplements in endurance-trained rats improve liver glutamine-GSH axis and modulate HSF1 pathway.


Asunto(s)
Suplementos Dietéticos , Glutamina/farmacología , Glutatión/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal , Resistencia Física/fisiología , Adaptación Fisiológica/efectos de los fármacos , Compuestos de Amonio/sangre , Animales , Glutamina/sangre , Glutamina/metabolismo , Disulfuro de Glutatión/metabolismo , Proteínas de Choque Térmico/metabolismo , Hígado/metabolismo , Masculino , Oxidación-Reducción , Ratas Wistar , Factores de Transcripción/metabolismo
4.
J Int Soc Sports Nutr ; 11(1): 61, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25530736

RESUMEN

Moderate and chronic bouts of exercise may lead to positive metabolic, molecular, and morphological adaptations, improving health. Although exercise training stimulates the production of reactive oxygen species (ROS), their overall intracellular concentration may not reach damaging levels due to enhancement of antioxidant responses. However, inadequate exercise training (i.e., single bout of high-intensity or excessive exercise) may result in oxidative stress, muscle fatigue and muscle injury. Moreover, during the recovery period, impaired immunity has been reported, for example; excessive-inflammation and compensatory immunosuppression. Nutritional supplements, sometimes referred to as immuno-nutrients, may be required to reduce immunosuppression and excessive inflammation. Herein, we discuss the action and the possible targets of key immuno-nutrients such as L-glutamine, L-arginine, branched chain amino acids (BCAA) and whey protein.

5.
Nutrition ; 30(5): 602-11, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24698353

RESUMEN

OBJECTIVE: The aim of the present study was to determine the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP) in endotoxemic mice. METHODS: B6.129 F2/J mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS], 5 mg/kg, LPS group) and orally supplemented for 48 h with either L-glutamine (1 g/kg) plus L-alanine (0.61 g/kg) (GLN+ALA-LPS group) or 1.49 g/kg DIP (DIP-LPS group). Plasma glutamine, cytokines, and lymphocyte proliferation were measured. Liver and skeletal muscle glutamine, glutathione (GSH), oxidized GSH (GSSG), tissue lipoperoxidation (TBARS), and nuclear factor (NF)-κB-interleukin-1 receptor-associated kinase 1 (IRAK1)-Myeloid differentiation primary response gene 88 pathway also were determined. RESULTS: Endotoxemia depleted plasma (by 71%), muscle (by 44%), and liver (by 49%) glutamine concentrations (relative to the control group), which were restored in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Supplemented groups reestablished GSH content, intracellular redox status (GSSG/GSH ratio), and TBARS concentration in muscle and liver (P < 0.05). T- and B-lymphocyte proliferation increased in supplemented groups compared with controls and LPS group (P < 0.05). Tumor necrosis factor-α, interleukin (IL)-6, IL-1 ß, and IL-10 increased in LPS group but were attenuated by the supplements (P < 0.05). Endotoxemic mice exhibited higher muscle gene expression of components of the NF-κB pathway, with the phosphorylation of IκB kinase-α/ß. These returned to basal levels (relative to the control group) in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Higher mRNA of IRAK1 and MyD88 were observed in muscle of LPS group compared with the control and supplemented groups (P < 0.05). CONCLUSION: Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Endotoxemia/tratamiento farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Glutamina/uso terapéutico , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Suplementos Dietéticos , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Endotoxemia/complicaciones , Endotoxemia/microbiología , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/microbiología , Glutamina/metabolismo , Glutamina/farmacología , Glutatión/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/genética , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Lipopolisacáridos , Hígado/metabolismo , Linfocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos , Músculo Esquelético/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , ARN Mensajero/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico
6.
Life Sci ; 94(2): 130-6, 2014 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-24269578

RESUMEN

AIMS: We hypothesized that oral l-glutamine supplementations could attenuate muscle damage and oxidative stress, mediated by glutathione (GSH) in high-intensity aerobic exercise by increasing the 70-kDa heat shock proteins (HSP70) and heat shock factor 1 (HSF1). MAIN METHODS: Adult male Wistar rats were 8-week trained (60-min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were supplemented with either l-alanyl-l-glutamine dipeptide (1.5 g/kg, DIP) or a solution containing the amino acids l-glutamine (1g/kg) and l-alanine (0.67 g/kg) in their free form (GLN+ALA) or water (controls). KEY FINDINGS: Plasma from both DIP- and GLN+ALA-treated animals showed higher l-glutamine concentrations and reduced ammonium, malondialdehyde, myoglobin and creatine kinase activity. In the soleus and gastrocnemius muscle of both supplemented groups, l-glutamine and GSH contents were increased and GSH disulfide (GSSG) to GSH ratio was attenuated (p<0.001). In the soleus muscle, cytosolic and nuclear HSP70 and HSF1 were increased by DIP supplementation. GLN+ALA group exhibited higher HSP70 (only in the nucleus) and HSF1 (cytosol and nucleus). In the gastrocnemius muscle, both supplementations were able to increase cytosolic HSP70 and cytosolic and nuclear HSF1. SIGNIFICANCE: In trained rats, oral supplementation with DIP or GLN+ALA solution increased the expression of muscle HSP70, favored muscle l-glutamine/GSH status and improved redox defenses, which attenuate markers of muscle damage, thus improving the beneficial effects of high-intensity exercise training.


Asunto(s)
Alanina/farmacología , Dipéptidos/farmacología , Glutamina/farmacología , Proteínas de Choque Térmico/fisiología , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Administración Oral , Alanina/administración & dosificación , Animales , Creatina Quinasa/sangre , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/fisiología , Suplementos Dietéticos , Dipéptidos/administración & dosificación , Glutamina/administración & dosificación , Glutamina/sangre , Glutatión/metabolismo , Proteínas HSP70 de Choque Térmico/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/fisiología , Factores de Transcripción del Choque Térmico , Proteínas de Choque Térmico/efectos de los fármacos , Masculino , Malondialdehído/sangre , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Mioglobina/sangre , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Factores de Transcripción/efectos de los fármacos , Factores de Transcripción/fisiología
7.
Rev. bras. ciênc. esporte ; 35(4): 1071-1092, out.-dez. 2013. ilus, tab
Artículo en Portugués | LILACS | ID: lil-705350

RESUMEN

Exercícios físicos associados a uma dieta balanceada são importantes fatores para a promoção da saúde. Contudo, a realização de exercícios físicos intensos e prolongados ou de caráter exaustivo pode promover inflamação crônica, overtraining e maior susceptibilidade a infecções. Sendo causa ou consequência, um dos fatores que contribuem para estes efeitos é o aumento exacerbado da síntese de compostos pró-oxidantes, conhecidos como espécies reativas do oxigênio (ERO) e nitrogênio (ERN). O aumento de ERO e ERN pode reduzir a capacidade antioxidante corporal, situação conhecida como estresse oxidativo. O estresse oxidativo tem sido relacionado como promotor de lesões a diversos constituintes celulares, principalmente sobre as membranas, efeito denominado como peroxidação lipídica. Para neutralizar os efeitos das ERO e ERN, o organismo dispõe do sistema de defesa antioxidante, localizado em diferentes compartimentos celulares e com funções diversas. Estudos têm, cada vez mais, demonstrado que o sistema antioxidante pode ser influenciado por intervenções nutricionais específicas, dentre as quais se incluem vitaminas, minerais, flavonóides e aminoácidos. Considerando o fato de muitas pessoas iniciarem a prática de exercícios físicos a cada dia, e que muitas destas ultrapassam seus limites, esta revisão visa abordar os principais sítios de síntese de ERO e ERN durante exercícios físicos, bem como possíveis estratégias nutricionais e seus mecanismos de ação sobre o sistema de defesa antioxidante.


Physical exercises associated with a balanced diet are important factors for health promotion. However intense and prolonged or strenuous exercise may promote chronic inflammation, overtraining and increased susceptibility to infections. Being cause or consequence, one of the factors that contribute to deleterious effects is exacerbated increase in the synthesis of pro-oxidant compounds, known as reactive oxygen species (ROS) and nitrogen species (RNS). The increase of ROS and RNS may reduce the body antioxidant capability, a condition known as oxidative stress. Oxidative stress has been implicated as a promoter of injuries to various cellular constituents, especially on the membranes, an effect known as lipid peroxidation. To attenuate the effects of ROS and RNS, the body has the antioxidant defense system, located in different cellular compartments and with different functions. Studies have increasingly shown that the antioxidant system can be influenced by specific nutritional interventions, among which are included vitamins, minerals, flavonoids and amino acids. Considering the fact that thousands of people engage in the practice of physical exercise every day, and that many of them go beyond their limits, this review aims to address the major sites of synthesis of ROS during exercise and nutrition strategies and their possible mechanisms action on the antioxidant defense system.


Ejercicios físicos asociados con una dieta equilibrada son factores importantes para la promoción de la salud. Sin embargo el ejercicio intenso y prolongado puede promover la inflamación crónica, el sobreentrenamiento y el aumento de la susceptibilidad a las infecciones. Siendo causa o consecuencia, uno de los factores que contribuyen a los efectos nocivos es el aumento exagerado de la síntesis de compuestos pro-oxidantes, conocidos como especies reactivas del oxígeno (ERO) y nitrógeno (ERN). El aumento de ERO y ERN puede reducir la capacidad antioxidante del cuerpo, una condición conocida como estrés oxidativo. El estrés oxidativo ha sido implicado como un promotor de las lesiones de varios componentes celulares, especialmente en las membranas, un efecto conocido como la peroxidación lipídica. Para atenuar los efectos de los ERO y ERN, el cuerpo tiene el sistema de defensa antioxidante, ubicado en diferentes compartimentos celulares y con diferentes funciones. Los estudios han demostrado cada vez que el sistema antioxidante puede ser influenciado por intervenciones nutricionales específicas, entre las que se incluyen vitaminas, minerales, flavonoides y aminoácidos. Teniendo en cuenta el hecho de que miles de personas participan en la práctica de ejercicio físico todos los días, y que muchos de estos van más allá de sus límites, esta revisión tiene como objetivo abordar los principales sitios de síntesis de ERO durante el ejercicio y estrategias de nutrición y sus mecanismos de acción en el sistema de defensa antioxidante.

8.
São Paulo; s.n; s.n; 2013. 169 p. tab, graf, ilus.
Tesis en Portugués | LILACS | ID: biblio-837080

RESUMEN

A sepse é a principal causa de morte em unidades de terapia intensiva (UTIs) no mundo. A reduzida disponibilidade do aminoácido mais abundante do organismo, a glutamina contribui para o complicado estado catabólico da sepse. No presente estudo investigamos os efeitos da suplementação oral com L-glutamina e L-alanina (GLN+ALA), ambos na norma livre e como dipeptídeo, L-alanil-L-glutamina (DIP), sobre o eixo glutamina-glutationa (GSH), sistema imune, inflamação, proteínas de choque térmico (HSPs) e expressão de genes envolvidos com vias de sinalização proteica em animais endotoxêmicos. Camundongos C57/B6 foram submetidos à endotoxemia (Escherichia coli LPS, 5 mg.kg-1, grupo LPS) e suplementados por 48 horas com L-glutamina (1 g.kg-1) e L-alanina (0,61 g.kg-1, grupo GLN+ALA-LPS) ou 1,49 g.kg-1 de DIP (grupo DIP-LPS). A endotoxemia promoveu depleção da concentração de glutamina no plasma (71%), músculo esquelético (50%) e fígado (49%), quando comparado ao grupo CTRL, sendo restauradas nos grupos DIP-LPS e GLN+ALA-LPS (P<0,05), fato que atenuou a redução da GSH e o estado redox (taxa GSSG/GSH) em eritrócitos circulantes, musculo e fígado (P<0,05). A suplementação em animais endotoxêmicos resultou em uma upregulation dos genes GSR, GPX1 e GCLC no músculo e fígado. A concentração das citocinas plasmáticasTNF-α, IL-6, IL-1ß e IL-10 foi atenuada pelas suplementações, bem como a expressão de mRNAs envolvidos com a resposta inflamatória, ativadas pela via do NF-κB(P<0,05). Concomitantemente, verificou-se aumento da capacidade proliferativa de linfócitos T e B circulantes nos grupos GLN+ALA-LPS e DIP-LPS. A expressão de mRNAs e a concentração de HSPs no tecido muscular foi restabelecida pelas suplementações, contudo, a expressão mRNAs relacionados às vias de síntese e degradação proteica foi somente estimulada no tecido hepático(P<0,05). Os resultados do presente estudo demonstram que a suplementação por via oral com GLN+ALA ou DIP podem ser utilizados clinicamente como métodos nutricionais em reverter o quadro de depressão da disponibilidade de glutamina corporal da sepse induzida por LPS, tendo impacto no eixo glutamina-glutationa, sistema imune e inflamatório


Sepsis is the leading cause of death inintensive care units (ICUs) in the world.The availability ofthe most abundant amino acid in the body, glutamine, is reduced in this situation, fact that contribute to the complicated catabolic state of sepsis. In the present study, we investigated the effects of oral supplementation with L-glutamine and L-alanine (GLN+ALA), both in their free form and as a dipeptide, L-alanyl-L-glutamine (DIP) on glutamine-glutathione axis (GSH), immune and inflammatory system, heat shock proteins (HSPs) expression and gene expressions involved in protein signaling pathways during endotoxemia. C57/B6 mice were subjected to endotoxemia (Escherichia coli LPS, 5 mg.kg-1, LPS group) and supplemented for 48 hours with L-glutamine (1 g.kg-1) plus L-alanine(0.61 g.kg-1, GLN+ALA-LPS group) or 1.49 g.kg-1of DIP (DIP-LPS group). Endotoxemia promoted depletion glutamine concentration in plasma (71%), skeletal muscle (50%) and liver (49%), when compared to the CTRL group, and was restored in the DIP-LPS e GLN+ALA-LPS (P<0.05), fact that attenuate the reduction of GSH and the redox state (GSSG/GSH rate) in circulating erythrocytes, liver and muscle (P<0.05). Supplementations in endotoxemic mice resulted in upregulation of GSR, GCLC and GPX1 genes in muscle and liver. Plasma concentration of TNF-α, IL-6, IL-1ß and IL-10 were attenuated by supplementation as well as the expression of mRNAs involved in the inflammatory response, activated by NFκ-B pathway (P <0.05). At the same time, high proliferative capacity of circulating T and B lymphocytes GLN+ALA-LPS e DIP-LPS were observed. HSPs (protein and mRNAs) and in muscle were restored by the supplements, however, the mRNAs expression related to the synthesis and degradation of protein pathways was only stimulated in the liver (P <0.05). Our results demonstrate that oral supplementation with GLN+ALA or DIP can be used as clinically nutritional methods to reverse the depression of body glutamine availability during sepsis induced by LPS, impacting on the glutamine-glutathione axis, immune and inflammatory system


Asunto(s)
Animales , Ratones , Endotoxemia/sangre , Dipéptidos/efectos adversos , Glutamina/efectos adversos , Sistema Inmunológico/anomalías , Aminoácidos , Glutatión Transferasa , Proteínas de Choque Térmico , Enfermedades Nutricionales y Metabólicas
9.
Cell Biochem Funct ; 28(1): 24-30, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19885855

RESUMEN

In this study, we investigated the effect of the supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine on plasma levels markers of muscle damage and levels of pro-inflammatory cytokines and glutamine metabolism in rats submitted to prolonged exercise. Rats were submitted to sessions of swim training for 6 weeks. Twenty-one days prior to euthanasia, the animals were supplemented with DIP (n = 8) (1.5 g.kg(-1)), a solution of free L-glutamine (1 g.kg(-1)) and free L-alanine (0.61 g.kg(-1)) (G&A, n = 8) or water (control (CON), n = 8). Animals were killed at rest before (R), after prolonged exercise (PE-2 h of exercise). Plasma concentrations of glutamine, glutamate, tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2) and activity of creatine kinase (CK), lactate dehydrogenase (LDH) and muscle concentrations of glutamine and glutamate were measured. The concentrations of plasma TNF-alpha, PGE2 and the activity of CK were lower in the G&A-R and DIP-R groups, compared to the CON-R. Glutamine in plasma (p < 0.04) and soleus muscle (p < 0.001) was higher in the DIP-R and G&A-R groups relative to the CON-R group. G&A-PE and DIP-PE groups exhibited lower concentrations of plasma PGE2 (p < 0.05) and TNF-alpha (p < 0.05), and higher concentrations of glutamine and glutamate in soleus (p < 0.001) and gastrocnemius muscles (p < 0.05) relative to the CON-PE group. We concluded that supplementation with free L-glutamine and the dipeptide LL-alanyl-LL-glutamine represents an effective source of glutamine, which may attenuate inflammation biomarkers after periods of training and plasma levels of CK and the inflammatory response induced by prolonged exercise.


Asunto(s)
Dipéptidos/farmacología , Glutamina/farmacología , Mediadores de Inflamación/metabolismo , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal , Alanina/farmacología , Animales , Creatina Quinasa/sangre , Creatina Quinasa/metabolismo , Suplementos Dietéticos , Dinoprostona/sangre , Ácido Glutámico/sangre , Glutamina/sangre , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre
10.
Rev. bras. med. esporte ; 15(5): 392-397, set.-out. 2009. ilus, tab
Artículo en Portugués | LILACS | ID: lil-530153

RESUMEN

A glutamina é o aminoácido livre mais abundante no plasma e no tecido muscular. Nutricionalmente é classificada como um aminoácido não essencial, uma vez que pode ser sintetizada pelo organismo a partir de outros aminoácidos. A glutamina está envolvida em diferentes funções, tais como a proliferação e desenvolvimento de células, o balanço acidobásico, o transporte da amônia entre os tecidos, a doação de esqueletos de carbono para a gliconeogênese, a participação no sistema antioxidante e outras. Por meio de técnicas de biologia molecular, estudos demonstram que a glutamina pode também influenciar diversas vias de sinalização celular, em especial a expressão de proteínas de choque térmico (HSPs). As HSPs contribuem para a manutenção da homeostasia da célula na presença de agentes estressores, tais como as espécies reativas de oxigênio (ERO). Em situações de elevado catabolismo muscular, como após exercícios físicos intensos e prolongados, a concentração de glutamina pode tornar-se reduzida. A menor disponibilidade desse aminoácido pode diminuir a resistência da célula a lesões, levando a processos de apoptose celular. Por essas razões, a suplementação com L-glutamina, tanto na forma livre, quanto como dipeptídeo, tem sido investigada. Alguns aspectos bioquímicos, metabólicos e mecanismos moleculares da glutamina, bem como os efeitos de sua suplementação, são abordados no presente trabalho.


Glutamine is the most frequent free amino acid in the serum and muscular tissue. Nutritionally, it is classified as a non-essential amino acid, once it can be synthesized by the body from other amino acids. Glutamine is involved in different functions, such as cell proliferation and development, basic acid balance, ammonia transportation between tissues, carbon skeleton donation to the gluconeogenesis, participation in the antioxidant system, among others. Molecular biology techniques show that it may also influence several cell signaling ways, especially the expression of heat shock proteins (HSP). The HSPs contribute to the maintenance of the cellular homeostasis in the presence of stress agents such as oxygen reactive species (ORE). In situations of high cellular catabolism, as after intense and prolonged physical exercises, the glutamine concentration may become reduced. Lower availability of this amino acid may decrease the cell resistance to injuries, leading to cellular apoptosis processes. Therefore, L-glutamine supplementation either in free form or as dipeptide has been investigated. Some biochemical and metabolic aspects, molecular mechanism of glutamine, as well as the effects of its supplementation are approached in the present article.


Asunto(s)
Ejercicio Físico , Glutamina , Sistema Inmunológico , Apoyo Nutricional , Fenómenos Fisiológicos Nutricionales del Lactante , Proteínas de Choque Térmico
11.
Nutrition ; 25(4): 428-35, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19056244

RESUMEN

OBJECTIVE: We investigated the effect of supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine, both in the free form, on the plasma and tissue concentrations of glutamine, glutamate, and glutathione (GSH) in rats subjected to long-duration exercise. METHODS: Rats were subjected to sessions of swim training. Twenty-one days before sacrifice, the animals were supplemented with DIP (1.5 g/kg, n = 6), a solution of free L-glutamine (1 g/kg) and free L-alanine (0.61 g/kg; GLN + ALA, n = 6), or water (CON, n = 6). Animals were sacrificed before (TR, n = 6) or after (LD, n = 6) long-duration exercise. Plasma concentrations of glutamine, glutamate, glucose, and ammonia and liver and muscle concentrations of glutamine, glutamate, and reduced and oxidized (GSSG) GSH were measured. RESULTS: Higher concentrations of plasma glutamine were found in the DIP-TR and GLN + ALA-TR groups. The CON-LD group showed hyperammonemia, whereas the DIP-LD and GLN + ALA-LD groups exhibited lower concentrations of ammonia. Higher concentrations of glutamine, glutamate, and GSH/GSSG in the soleus muscle and GSH and GSH/GSSG in the liver were observed in the DIP-TR and GLN + ALA-TR groups. The DIP-LD and GLN + ALA-LD groups exhibited higher concentrations of GSH and GSH/GSSG in the soleus muscle and liver compared with the CON-LD group. CONCLUSION: Chronic oral administration of DIP and free GLN + ALA before long-duration exercise represents an effective source of glutamine and glutamate, which may increase muscle and liver stores of GSH and improve the redox state of the cell.


Asunto(s)
Dipéptidos/farmacología , Ácido Glutámico/metabolismo , Glutamina/farmacología , Glutatión/sangre , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal , Administración Oral , Alanina/administración & dosificación , Alanina/farmacología , Amoníaco/sangre , Animales , Suplementos Dietéticos , Dipéptidos/administración & dosificación , Glutamina/administración & dosificación , Glutamina/metabolismo , Hígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Ratas , Ratas Wistar
12.
Rev. bras. med. esporte ; 13(5): 336-342, set.-out. 2007. ilus
Artículo en Portugués | LILACS | ID: lil-483325

RESUMEN

As espécies reativas de oxigênio (ERO) são normalmente produzidas pelo metabolismo corporal. Todavia, ERO apresentam a capacidade de retirar elétrons de outros compostos celulares, sendo capazes de provocar lesões oxidativas em várias moléculas, fato que leva à perda total da função celular. A realização de exercícios físicos aumenta a síntese de ERO, além de promover lesão muscular e inflamação. Após uma sessão de exercícios físicos, inicia-se normalmente a fase de recuperação, quando são observados diversos efeitos positivos à saúde, incluindo o aumento da resistência a novas lesões induzidas ou não por exercícios, fato que é considerado como um processo "adaptativo". Diversos estudos, porém, relatam que essa recuperação não é alcançada por indivíduos que se submetem a exercícios intensos e prolongados, ou, ainda, que possuem elevada freqüência de treinamento. Alternativas nutricionais têm sido muito estudadas, a fim de reduzir os efeitos promovidos pelo exercício extenuante, dentre as quais está a suplementação com vitamina E, vitamina C, creatina e glutamina. Esta revisão tem como objetivo abordar os aspectos atuais envolvendo a formação das ERO, os processos de lesão celular e inflamação, a adaptação aos tipos de exercício aeróbio e anaeróbio e possíveis intervenções nutricionais.


Oxygen reactive species (ORE) are usually produced by the body metabolism. However, ORE present the ability to remove electrons from other cellular composites, being able to cause oxidative injuries in several molecules. Such fact leads to a total loss of cellular function. Physical exercise practice increases ORE synthesis, besides promoting muscular injury and inflammation. After a physical exercise set, the recovery phase begins, where several effects positive to health are observed, including increase in resistance to new injuries induced or not by exercise, a fact which is considered an 'adaptation' process. Many studies though, have reported that this recovery is not reached by individuals who are submitted to intense and extended exercises, or even, who have high training frequency. Nutritional alternatives have been widely studied, in order to reduce the effects promoted by extenuating exercise, among which vitamin E, vitamin C, creatine and glutamine supplementation is included. This review has the aim to approach the current aspects concerning the ORE formation, the cellular injury and inflammation processes, the adaptation to the kinds of aerobic and anaerobic exercise, besides possible nutritional interventions.

13.
Nutrition ; 22(5): 520-7, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16600817

RESUMEN

OBJECTIVE: Acute administration of leucine has been shown to stimulate certain protein synthesis related anabolic processes. However, the effect of chronic leucine administration in a catabolic situation caused by food restriction (FR) has not been established. We therefore evaluated the effect of chronic leucine supplementation on the body composition and some indicators of protein nutritional status of rats submitted to FR. METHODS: Adult male Wistar rats were submitted to 50% FR for 6 weeks. The control group received the AIN-93M diet and the leucine group received the same diet supplemented with 5.91 g L-leucine/kg ration. We then determined carcass chemical composition, serum leptin, albumin and total protein concentrations, and protein, DNA and RNA concentrations in gastrocnemius muscle and liver. RESULTS: No difference in final body weight was observed between groups. However, the leucine group presented a lower amount of body fat (P < 0.05). Leptin concentration showed a directly proportional correlation with the amount of body fat (r = 0.88, P < 0.05), but no significant difference in serum leptin concentration was observed between groups (P = 0.08). Regarding protein nutritional status, liver protein concentration was higher in the leucine group (P < 0.05). In the gastrocnemius muscle, a higher RNA concentration (P < 0.05) and a tendency towards higher DNA concentration (P = 0.06) were observed in the leucine group. CONCLUSION: The results indicate that low-dose leucine supplementation increases body fat loss and improves liver protein status and the capacity of muscle protein synthesis in rats submitted to FR.


Asunto(s)
Composición Corporal/efectos de los fármacos , Restricción Calórica , Leucina/administración & dosificación , Hígado/metabolismo , Proteínas Musculares/biosíntesis , Músculo Esquelético/metabolismo , Tejido Adiposo/metabolismo , Animales , Suplementos Dietéticos , Leptina/sangre , Leucina/farmacología , Hígado/efectos de los fármacos , Masculino , Músculo Esquelético/efectos de los fármacos , Estado Nutricional , Proteínas/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Albúmina Sérica/metabolismo , Pérdida de Peso/fisiología
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