L-glutamina e zinco em dietas para frangos de corte criados em condições naturais de calor / L-glutamine and zinc in diets for chickens created under natural conditions of heat

Objetivou-se avaliar a suplementação de L-glutamina e zinco em dietas para frangos de corte criados em condições naturais de calor sobre o desempenho produtivo nos períodos de 1 a 7 e de 1 a 21 dias de idade; e o peso dos órgãos digestivos e do coração aos 21 dias de idade. Foram utilizados 630 pintos de corte da linhagem Ross, distribuídos em delineamento inteiramente casualizados em esquema 2 (1 e 2% de L-glutamina) x 3 (0, 90, e 120 mg de zinco/kg de ração) + 1 (dieta controle), totalizando sete tratamentos e cinco repetições com 18 aves cada. A suplementação combinada de L-glutamina e zinco não influenciou as variáveis avaliadas, porém a suplementação isolada de L-glutamina proporcionou maior viabilidade criatória e índice de eficiência produtiva, além de maior peso de fígado e moela dos animais. Da mesma forma, o zinco de forma isolada interferiu de maneira linear decrescente nos pesos relativos do fígado, moela, pâncreas e coração. Concluem-se que dietas suplementadas com1% de L-glutamina melhoram a viabilidade criatória, o índice de eficiência produtiva, o peso de fígado e moela de frangos de corte na fase de 1 a 21 dias de idade, bem como que a adição de zinco interfere no peso dos órgãos digestivos e coração das aves criadas em condições naturais de calor.(AU)

The objective of this study was to evaluate the supplementation of L-glutamine and zinc in diets for broilers reared in natural conditions of heat on the productive performance in the periods from 1 to 7 and from 1 to 21 days of age and, weight of digestive organs and heart at 21 days of age. Six hundred and thirty Ross broiler chicks were used, distributed in a completely randomized design, in scheme 2 (1 and 2% L-glutamine) x 3 (0, 90, and 120 mg of zinc/kg of feed) + 1 (diet control), totaling seven treatments and five repetitions, with 18 birds each. The combined supplementation of L-glutamine and zinc did not influence the variables evaluated, however the isolated supplementation of L-glutamine provided greater creative viability and productive efficiency index in addition toa greater weight of liver and gizzard of the animals. Likewise, zinc alone interfered in a linear decreasing manner on the relative weights of the liver, gizzard, pancreas and heart. Diets supplemented with 1% L-glutamine improve the creative viability, the production efficiency index, the weight of liver and gizzards of broilers in the phase from1 to 21 days of age and the addition of zinc interferes in the weight of the digestive organs and heart of birds raised in natural heat.(AU)

L-glutamina e zinco em dietas para frangos de corte criados em condições naturais de calor / L-glutamine and zinc in diets for chickens created under natural conditions of heat

Objetivou-se avaliar a suplementação de L-glutamina e zinco em dietas para frangos de corte criados em condições naturais de calor sobre o desempenho produtivo nos períodos de 1 a 7 e de 1 a 21 dias de idade; e o peso dos órgãos digestivos e do coração aos 21 dias de idade. Foram utilizados 630 pintos de corte da linhagem Ross, distribuídos em delineamento inteiramente casualizados em esquema 2 (1 e 2% de L-glutamina) x 3 (0, 90, e 120 mg de zinco/kg de ração) + 1 (dieta controle), totalizando sete tratamentos e cinco repetições com 18 aves cada. A suplementação combinada de L-glutamina e zinco não influenciou as variáveis avaliadas, porém a suplementação isolada de L-glutamina proporcionou maior viabilidade criatória e índice de eficiência produtiva, além de maior peso de fígado e moela dos animais. Da mesma forma, o zinco de forma isolada interferiu de maneira linear decrescente nos pesos relativos do fígado, moela, pâncreas e coração. Concluem-se que dietas suplementadas com1% de L-glutamina melhoram a viabilidade criatória, o índice de eficiência produtiva, o peso de fígado e moela de frangos de corte na fase de 1 a 21 dias de idade, bem como que a adição de zinco interfere no peso dos órgãos digestivos e coração das aves criadas em condições naturais de calor.

The objective of this study was to evaluate the supplementation of L-glutamine and zinc in diets for broilers reared in natural conditions of heat on the productive performance in the periods from 1 to 7 and from 1 to 21 days of age and, weight of digestive organs and heart at 21 days of age. Six hundred and thirty Ross broiler chicks were used, distributed in a completely randomized design, in scheme 2 (1 and 2% L-glutamine) x 3 (0, 90, and 120 mg of zinc/kg of feed) + 1 (diet control), totaling seven treatments and five repetitions, with 18 birds each. The combined supplementation of L-glutamine and zinc did not influence the variables evaluated, however the isolated supplementation of L-glutamine provided greater creative viability and productive efficiency index in addition toa greater weight of liver and gizzard of the animals. Likewise, zinc alone interfered in a linear decreasing manner on the relative weights of the liver, gizzard, pancreas and heart. Diets supplemented with 1% L-glutamine improve the creative viability, the production efficiency index, the weight of liver and gizzards of broilers in the phase from1 to 21 days of age and the addition of zinc interferes in the weight of the digestive organs and heart of birds raised in natural heat.

Effects of Glutamine on Digestive Function and Redox Regulation in the Intestines of Broiler Chickens Challenged with Salmonella Enteritidis

The aim was to investigate the effect of glutamine (Gln) on broilers challenged with Salmonella Enteritidis. 240 1-day-old birds were divided into four groups in a completely randomized design, each of which included 6 replicates with 10 birds per replicate. Group I served as the unchallenged, untreated control (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. Birds in group III and IV were treated with 0.5% (Gln 1) and 1.0% (Gln 2), respectively, of Gln. The results indicated that S. Enteritidis infection led to a decrease in the average body weight at d 7, 14, and 21 (p 0.05). Chickens fed the Gln showed improved average body weights in comparison with the SCC group (p 0.05). At d 4, 7, 14, and 21, the Gln groups increased digestive enzyme (trypsin, lipase and amylase (except the amylase activity of jejunum at d 14 and d 21)) activities in the intestine (p 0.05), superoxide dismutase (SOD) (at d 14 jejunum; except at d 4, ileum) and catalase (CAT) (at d 4, and d 21, jejunum; d 4, ileum) activity in the serum (except at d 14) and intestinal mucosa (p 0.05), and the mRNA expression of SOD, CAT and nuclear respiratory factor 2 (Nrf2) of the intestinal mucosa compared with the SCC group (p 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of S. Enteritidis infection of broilers.(AU)

Effects of Glutamine on Digestive Function and Redox Regulation in the Intestines of Broiler Chickens Challenged with Salmonella Enteritidis

The aim was to investigate the effect of glutamine (Gln) on broilers challenged with Salmonella Enteritidis. 240 1-day-old birds were divided into four groups in a completely randomized design, each of which included 6 replicates with 10 birds per replicate. Group I served as the unchallenged, untreated control (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. Birds in group III and IV were treated with 0.5% (Gln 1) and 1.0% (Gln 2), respectively, of Gln. The results indicated that S. Enteritidis infection led to a decrease in the average body weight at d 7, 14, and 21 (p 0.05). Chickens fed the Gln showed improved average body weights in comparison with the SCC group (p 0.05). At d 4, 7, 14, and 21, the Gln groups increased digestive enzyme (trypsin, lipase and amylase (except the amylase activity of jejunum at d 14 and d 21)) activities in the intestine (p 0.05), superoxide dismutase (SOD) (at d 14 jejunum; except at d 4, ileum) and catalase (CAT) (at d 4, and d 21, jejunum; d 4, ileum) activity in the serum (except at d 14) and intestinal mucosa (p 0.05), and the mRNA expression of SOD, CAT and nuclear respiratory factor 2 (Nrf2) of the intestinal mucosa compared with the SCC group (p 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of S. Enteritidis infection of broilers.

Effect of dietary glutamine supplementation associated with threonine levels in the intestinal mucosa of broilers challenged with Eimeria sp. from 22 to 42 days of age / Efeito da suplementação de glutamina em dietas associadas com níveis de treonina sobre a mucosa intestinal de frangos de corte desafiados com Eimeria sp., de 22 a 42 dias de idade

The aim of this study was to evaluate the effects of glutamine and threonine supplementation on the ileal mucosa of broilers aged 21-42 days. Six-hundred and forty-one-day old chicks of the Cobb Slow lineage were utilized in this study. From 1 to 21 days of age, the chicks received a commercial diet; and after 22 days, the broilers were distributed in a completely randomized design in a 2 × 4 factorial scheme (challenge and diet), with 4 replications and 20 chicks per experimental unit. At 22 days of age, the challenged broilers received a commercial vaccine against coccidiosis. A commercial diet was utilized as control and three other diets were formulated with reduced crude protein (-3%), and were corrected with the addition of glutamine (Gln) and glutamic acid (Glu) as non-specific nitrogen sources, and finally supplemented with L-Threonine (Thr) at 0.70, 0.80, and 0.85% digestible threonine, respectively. At 28 days of age, diets with Gln/Glu + Thr resulted in greater ileal villi lengths. Challenge with Eimeria sp. reduced the number of goblet cells and increased the duodenal and jejunal crypt depths. At 42 days of age, an interaction was observed between diet and challenge in relation to ileal villi length; better results were observed in the challenged broilers that received 0.85% Gln/Glu + Thr. The mucosal morphology in the ileal villi extremities was preserved in the challenged broilers that received higher Thr levels in their diets. The results suggested that the inclusion of glutamine and threonine affected the morphometry and mucosa of the ileum, thereby improving the mucosal quality.(AU)

O objetivo deste estudo foi avaliar os efeitos da suplementação de glutamina e treonina sobre a mucosa ileal de frangos de corte de 21 a 42 dias de idade. Foram utilizados 640 pintos da linhagem Cobb Slow. De 1 a 21 dias de idade, as aves receberam dieta comercial, e a partir de 22 dias foram distribuídas em um delineamento completamente casualizado seguindo um esquema fatorial 2 x 4 (desafio e dieta), com 4 repetições e 20 aves por unidade experimental. As aves foram desafiadas através da vacina de coccidiose. A dieta comercial foi utilizada como controle, e três outras dietas foram formuladas com proteína bruta reduzida (-3%) e corrigidas com a adição de glutamina e ácido glutâmico como fontes de nitrogênio não especificas, e então suplementadas com L-treonina, totalizando 0.70, 0.80 e 0.85% de treonina digestível, respectivamente. Aos 28 dias de idade, dietas com Gln/Glu+Thr mostraram maiores comprimentos de vilo na região do íleo, e o desafio com Eimeria sp reduziu o número de células caliciformes e aumentou a profundidade das criptas do duodeno e do íleo. Aos 42 dias de idade, houve uma interação entre dieta e desafio com relação ao comprimento do vilo do íleo, apresentando melhores resultados em aves desafiadas que receberam a dieta com 0.85% Gln/Glu+Thr. A morfologia da mucosa em região de extremidades de vilos no íleo foi preservada em aves desafiadas que receberam o maior nível de treonina na dieta. Os resultados sugerem que a inclusão de níveis de glutamina e treonina influenciaram a morfometria ileal, melhorando assim a qualidade da mucosa.(AU)

Effect of dietary glutamine supplementation associated with threonine levels in the intestinal mucosa of broilers challenged with Eimeria sp. from 22 to 42 days of age / Efeito da suplementação de glutamina em dietas associadas com níveis de treonina sobre a mucosa intestinal de frangos de corte desafiados com Eimeria sp., de 22 a 42 dias de idade

The aim of this study was to evaluate the effects of glutamine and threonine supplementation on the ileal mucosa of broilers aged 21-42 days. Six-hundred and forty-one-day old chicks of the Cobb Slow lineage were utilized in this study. From 1 to 21 days of age, the chicks received a commercial diet; and after 22 days, the broilers were distributed in a completely randomized design in a 2 × 4 factorial scheme (challenge and diet), with 4 replications and 20 chicks per experimental unit. At 22 days of age, the challenged broilers received a commercial vaccine against coccidiosis. A commercial diet was utilized as control and three other diets were formulated with reduced crude protein (-3%), and were corrected with the addition of glutamine (Gln) and glutamic acid (Glu) as non-specific nitrogen sources, and finally supplemented with L-Threonine (Thr) at 0.70, 0.80, and 0.85% digestible threonine, respectively. At 28 days of age, diets with Gln/Glu + Thr resulted in greater ileal villi lengths. Challenge with Eimeria sp. reduced the number of goblet cells and increased the duodenal and jejunal crypt depths. At 42 days of age, an interaction was observed between diet and challenge in relation to ileal villi length; better results were observed in the challenged broilers that received 0.85% Gln/Glu + Thr. The mucosal morphology in the ileal villi extremities was preserved in the challenged broilers that received higher Thr levels in their diets. The results suggested that the inclusion of glutamine and threonine affected the morphometry and mucosa of the ileum, thereby improving the mucosal quality.

O objetivo deste estudo foi avaliar os efeitos da suplementação de glutamina e treonina sobre a mucosa ileal de frangos de corte de 21 a 42 dias de idade. Foram utilizados 640 pintos da linhagem Cobb Slow. De 1 a 21 dias de idade, as aves receberam dieta comercial, e a partir de 22 dias foram distribuídas em um delineamento completamente casualizado seguindo um esquema fatorial 2 x 4 (desafio e dieta), com 4 repetições e 20 aves por unidade experimental. As aves foram desafiadas através da vacina de coccidiose. A dieta comercial foi utilizada como controle, e três outras dietas foram formuladas com proteína bruta reduzida (-3%) e corrigidas com a adição de glutamina e ácido glutâmico como fontes de nitrogênio não especificas, e então suplementadas com L-treonina, totalizando 0.70, 0.80 e 0.85% de treonina digestível, respectivamente. Aos 28 dias de idade, dietas com Gln/Glu+Thr mostraram maiores comprimentos de vilo na região do íleo, e o desafio com Eimeria sp reduziu o número de células caliciformes e aumentou a profundidade das criptas do duodeno e do íleo. Aos 42 dias de idade, houve uma interação entre dieta e desafio com relação ao comprimento do vilo do íleo, apresentando melhores resultados em aves desafiadas que receberam a dieta com 0.85% Gln/Glu+Thr. A morfologia da mucosa em região de extremidades de vilos no íleo foi preservada em aves desafiadas que receberam o maior nível de treonina na dieta. Os resultados sugerem que a inclusão de níveis de glutamina e treonina influenciaram a morfometria ileal, melhorando assim a qualidade da mucosa.

Efeito da suplementação com L-glutamina e L-alanina, livres ou como dipeptídeo, sobre a lesão, inflamação e citoproteção em modelos de estresse in vivo e in vitro / Effects of supplementation with L-glutamine and L-alanine, in their free form or as dipeptide, on muscle damage, inflammation and cytoprotection of in vivo and in vitro stress models

Subprojeto 1: Determinação do efeito anti-inflamatório e citoprotetor da suplementação com L-glutamina e L-alanina, ou com L-alanil-L-glutamina (DIP) em ratos submetidos a treinamento resistido. Exercícios intensos reduzem a disponibilidade de glutamina, comprometendo a função imune e a recuperação de atletas. O objetivo do estudo foi avaliar os efeitos da suplementação oral crônica com L-glutamina e L-alanina, nas formas livres ou como dipeptídeo (DIP), sobre parâmetros de lesão, inflamação e citoproteção em ratos Wistar adultos submetidos a treinamento resistido (TR). Neste estudo, o TR reduziu a concentração de glutamina no plasma e no músculo EDL. No entanto, este efeito foi atenuado pelos suplementos contendo L-glutamina, os quais aumentaram os conteúdos da proteína de resposta ao estresse (HSP70) em células do sistema imune (PBMC) e no EDL, concomitantemente à redução da ativação do NF-kB e a da concentração de citocinas no EDL. O efeito protetor das suplementações também foi evidenciado pela atenuação de marcadores de lesão (CK e LDH) e inflamação (TNF-α e IL-1ß), bem como pelo aumento nas concentrações de marcadores anti-inflamatórios (IL-6, IL-10 e MCP-1) no plasma. Nossos resultados sugerem que a suplementação oral crônica com L-glutamina (administrada com L-alanina livre ou como DIP) promoveu efeitos citoprotetores mediados pela HSP70 em resposta à lesão e inflamação induzidas pelo TR. Subprojeto 2: Efeitos da L-alanil-L-glutamina sobre as vias de sinalização da insulina e da mTOR/S6K, e citoproteção em células musculoesqueléticas C2C12. O dipeptídeo L-alanil-L-glutamina é conhecido por modular o metabolismo e a viabilidade celular. Contudo, os efeitos sobre os componentes clássicos das vias de sinalização da insulina e da mTOR/S6K, bem como o efeito citoprotetor em células musculares, são pouco esclarecidos. O objetivo deste estudo foi investigar o efeito do DIP sobre as vias de sinalização da insulina e da mTOR/S6K em miotubos C2C12, em condições normais ou resistentes à insulina. A exposição crônica à insulina (24h) promoveu resistência à insulina, reduzindo os conteúdos totais do receptor beta (IR-ß) e do substrato do receptor de insulina (IRS-1), e diminuindo a fosforilação de IRS-1, AKT e P44/42 MAPK. Adicionalmente, houve redução na expressão do transportador de glicose (GLUT4) e HSP70, redução da viabilidade celular e menor fosforilação de p70S6k e S6, proteínas relacionadas à síntese proteica. Em contraste, a suplementação com DIP aumentou os conteúdos totais de IR-ß e IRS-1 e a fosforilação de IRS-1 e AKT. A glicólise anaeróbia e a capacidade glicolítica, além da fosforilação de p70S6k e S6, foram aumentadas pelo DIP em condições normais e na resistência à insulina. Nestas condições experimentais, nossos resultados sugerem que a suplementação com DIP melhorou as vias de sinalizações da insulina e da mTOR/S6K, aumentou a captação e metabolização da glicose, independente da estimulação com insulina e, finalmente, promoveu citoproteção resgatando parcialmente as células de um estado resistente à insulina, por meio do aumento de HSP70 e ativação das etapas finais da via mTOR/S6K.

Subproject 1: Determination of the anti-inflammatory and cytoprotective effects of supplementation with L-glutamine and L-alanine, or with L-alanyl-L-glutamine in rats submitted to resistance training. Intense exercise reduces glutamine availability, compromising immune function and recovery of athletes. The objective of the study was to evaluate the effects of chronic oral supplementation with L-glutamine and L-alanine, in their free form or as dipeptide (DIP), on muscle damage, inflammation and cytoprotection in adult Wistar rats submitted to resistance training (RT). In this study, RT reduced glutamine concentration in plasma and EDL muscle. However, this effect was attenuated by supplements containing L-glutamine, which increased the contents of the stress response protein (HSP70) in immune system cells (PBMC) and EDL, concomitantly with the reduction of NF-kB activation and the concentration of cytokines in EDL. The protective effect of supplementation was also evidenced by attenuation of lesion markers (CK and LDH) and inflammation (TNF-α and IL-1ß), as well as by the increase in anti-inflammatory plasma markers (IL-6, IL-10 and MCP-1). Our results suggest that chronic oral supplementation with L-glutamine (administered along with free L-alanine or as DIP) promoted HSP70-mediated cytoprotective effects in response to RT-induced injury and inflammation. Subproject 2: Effects of L-alanyl-L-glutamine on the components of insulin and mTOR/ S6K signaling pathways and cytoprotection in C2C12 musculoskeletal cells. The dipeptide L-alanyl-L-glutamine is known to modulate metabolism and cell viability. However, the effects on the classical components of insulin and mTOR/ S6K signaling pathways, as well as the cytoprotective effect on muscle cells, are poorly understood. The aim of this study was to investigate the effect of DIP on insulin and mTOR/ S6K signaling pathways in C2C12 myotubes, under normal or insulin resistant conditions. Chronic insulin exposure (24h) promoted insulin resistance, reducing the total contents of the insulin receptor (IR-ß) and the insulin receptor substrate (IRS-1), and decreasing the phosphorylation of IRS-1, AKT and P44/ 42 MAPK. In addition, there was a reduction in the expression of glucose transporter (GLUT4) and HSP70, reduction of cell viability and defective phosphorylation of p70S6k and S6, which are related to protein synthesis. On the other hand, DIP supplementation increased the total contents of IR-ß and IRS-1 and the phosphorylation of IRS-1 and AKT. Anaerobic glycolysis and glycolytic capacity, in addition to phosphorylation of p70S6k and S6, were increased by DIP under normal conditions and in insulin resistance. In our experimental conditions, our results suggest that DIP supplementation improved the signaling pathways of insulin and mTOR/ S6K, increased glucose uptake and metabolism, independent of insulin stimulation, and finally promoted cytoprotection by partially rescuing the cells of an insulin resistant state, by increasing HSP70 and activating the final stages of the mTOR/ S6K pathway.

Avaliação do controle da expressão gênica de citocinas pró inflamatórias mediado pela IL-10. Participação da IL-10 na modulação da resposta inflamatória exercida pela glutamina e na restrição alimentar / Proinflammatory cytokines gene expression control mediated by IL-10. Participation of IL-10 on inflammatory response exerted by glutamine and dietary restriction

O desenvolvimento de uma resposta imune adequada é um processo extremamente importante para a manutenção da homeostase do organismo. Uma série de processos são desencadeados a partir do primeiro contato com micro-organismos patógenos até a efetivação da resposta imune de memória. Todos esses processos envolvem a participação e a complexa atuação de mediadores como as citocinas inflamatórias e também citocinas regulatórias, que exercerão efeitos controlando o processo inflamatório. Diversos mecanismos moleculares, subjacentes à resposta inflamatória, ainda não estão totalmente compreendidos, como por exemplo o controle da expressão de genes inflamatórios exercido pela IL-10. Os processos envolvidos na resposta inflamatória são mantidos às custas do consumo de nutrientes, dentre eles podemos destacar o aminoácido glutamina, que atua em nível molecular, fornecendo nitrogênio para a formação do material genético e fonte energética para determinadas células do sistema imunológico como os macrófagos. Portanto, neste trabalho, investigamos os efeitos da IL-10 na modificação de nucleossomos, evidenciando o papel dessa citocina em regular a expressão de genes inflamatórios em macrófagos. Avaliamos também a função da glutamina, modulando a expressão de RNAm de citocinas inflamatórias e regulatórias dessas células. E por último, desenvolvemos um modelo de restrição alimentar em camundongos, nos quais avaliamos os efeitos desse modelo considerando-se alguns aspectos hematológicos e estudamos as alterações na resposta inflamatória em células esplênicas e do peritônio, bem como avaliamos a suplementação de glutamina in vitro na produção das citocinas (IL-12, TNF-alfa, IL-10) e a expressão do fator de transcrição NFkB. Os resultados compilados mostraram que a IL-10 leva a uma rápida redução da acetilação de nucleossomos, modulando a arquitetura da cromatina de genes inflamatórios como a IL-12. A glutamina modula a expressão de citocinas inflamatórias, regulando positivamente a expressão de IL-10 e Interferon beta. E a restrição alimentar induz a redução de citocinas proinflamatórias (IL-12 e TNF-α), influenciadas pelo aumento da produção de IL-10 e finalmente a suplementação com glutamina não interfere nesses parâmetros nas células peritoneiais e esplênicas do grupo submetido à restrição alimentar. Conclusão: a IL-10 modula a expressão gênica através da modificação de nucleossomos em macrófagos derivados da medula; a glutamina modula a expressão de IL-10 inibindo a resposta inflamatória, e a restrição alimentar modula alguns aspectos hematológicos e possui propriedades anti-inflamatórias

The development of an appropriate immune response is an important process to the organism's homeostatic maintenance. A series of processes are triggered upon the very first contact with pathogens, up to the immunological memory establishment. These processes implicate in the participation of complex mediators, such as inflammatory and regulatory cytokines that will control the inflammatory process. Some mechanisms underlying the inflammatory response are not totally understood, the control of inflammatory genes exerted by IL-10 is an example. The processes involved in the inflammatory response are kept with nutrients expense, among these nutrients we can highlight the amino acid glutamine. It acts in a molecular level, supplying nitrogen to genetic material formation and as an energy supply for immune cells such as macrophages. Thus, we investigated the IL-10 effects on nucleosome modifications evidencing this cytokine role regulating inflammatory genes expression in macrophages. We also evaluated glutamine functions modulating inflammatory and regulatory cytokines mRNA expression on these cells. Ultimately, we developed a dietary restriction animal model where we evaluated it's effects on selected haematological aspects, analyzing the alteration in the inflammatory response of splenic and peritoneal cells. We also evaluated in vitro glutamine supplementation assessing cytokines production (IL-12, TNF-α, and IL-10) and the expression of NFkB transcription factor. The compiled results a expressive reduction in nucleosome acetylation modifying the chromatin architecture of inflammatory genes such as IL-12 and IL-6. Glutamine modulates inflammatory cytokines gene expression upregulating the expression of IL-10 and interferon beta. The dietary restriction reduces proinflammatory cytokines production (IL-12 and TNF-α), these results are influenced by the upregulated IL-10 production, glutamine supplementation have no effect on these parameters in the dietary restriction group. In conclusion, we can infer that IL-10 modulates gene expression trough nucleosome modification in bone marrow derived macrophages, glutamine has a potential effect on IL-10 expression, inhibiting the inflammatory response and dietary restriction modifies hematological parameters, presenting anti-inflammatory properties

Effects of glutamine on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis

This study aimed to assess the effects of glutamine as feed additive on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis. A total of 400 day-old male chicks were randomly assigned to four treatments (NVNG no vaccination, no glutamine supplementation; NVG no vaccination, glutamine supplementation (10 g kg1); VNG vaccination, no glutamine supplementation; VG vaccination, glutamine supplementation) replicated four times with 25 birds per replicate. A commercial sprayed-on vaccine against coccidiosis containing Eimeria acervulina, E. maxima, E. mivati, and E. tenella was administered at the hatchery. Broiler performance was evaluated from 1-28 days, and morphometric parameters were analyzed at 14, 21, and 28 days of age. Body weight gain and feed intake were negatively affected by vaccination, but not by glutamine. Vaccination increased crypt depth in the duodenum and jejunum at 21 and 28 days. In conclusion, this study showed that glutamine was not able to increase weight gain of broiler chickens, irrespective of whether the animals were vaccinated or not against coccidiosis. Glutamine supplementation was able to improve feed conversion in vaccinated birds suggesting trophic effect on intestinal epithelium improving.

Effects of glutamine on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis

This study aimed to assess the effects of glutamine as feed additive on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis. A total of 400 day-old male chicks were randomly assigned to four treatments (NVNG no vaccination, no glutamine supplementation; NVG no vaccination, glutamine supplementation (10 g kg1); VNG vaccination, no glutamine supplementation; VG vaccination, glutamine supplementation) replicated four times with 25 birds per replicate. A commercial sprayed-on vaccine against coccidiosis containing Eimeria acervulina, E. maxima, E. mivati, and E. tenella was administered at the hatchery. Broiler performance was evaluated from 1-28 days, and morphometric parameters were analyzed at 14, 21, and 28 days of age. Body weight gain and feed intake were negatively affected by vaccination, but not by glutamine. Vaccination increased crypt depth in the duodenum and jejunum at 21 and 28 days. In conclusion, this study showed that glutamine was not able to increase weight gain of broiler chickens, irrespective of whether the animals were vaccinated or not against coccidiosis. Glutamine supplementation was able to improve feed conversion in vaccinated birds suggesting trophic effect on intestinal epithelium improving.(AU)

Effects of Dietary L-Glutamine or L-Glutamine Plus L-Glutamic Acid Supplementation Programs on the Performance and Breast Meat Yield Uniformity of 42-d-Old Broilers

This study aimed at evaluating four dietary L-Glutamine (L-Gln) or L-Gln plus L-Glutamate (L-Glu) supplementation programs on the performance, breast yield, and uniformity of broilers. A total of 2,112 one-d-old male Cobb 500(r) broilers were distributed according to a randomized block design in a 2 × 4 factorial arrangement (L-Gln or L-Gln plus L-Glu × 4 supplementation programs), totaling eight treatments with 12 replicates of 22 broilers each. The supplementation programs consisted of the dietary inclusion or not of 0.4% of L-Gln or L-Gln plus L-Glu for four different periods: 0 days (negative control), 9d, 21d, and 42d. Feed intake (FI, g), body weight gain (BWG, g), feed conversion ratio (FCR, kg/kg), coefficient of variation of body weight (CV, %), body weight uniformity (UNIF, %), breast weight (BW, g), breast yield (BY, %), coefficient of variation of breast weight (CVB), breast uniformity (UNIFB), coefficient of variation of breast yield (CVBY), and breast yield uniformity (UNIFBY) were evaluated. Birds fed the diets treatments supplemented with L-Gln or L-Gln plus L-Glu for 9d presented 3% higher BWG (p<0.05) compared with the controls. The L-Gln or L-Gln plus L-Glu supplementation until broilers were 21 days old resulted in 14, 10, 16, and 12% improvements (p<0.05) in CV, UNIF, CVBY, UNIFBY, respectively. The supplementation of 0.4% L-Gln (L-Gln 99%) or L-Gln plus L-Glu (minimum 95%) to pre-starter and starter broiler diets is recommended to improve body weight gain and uniformity.(AU)

Effects of Dietary L-Glutamine or L-Glutamine Plus L-Glutamic Acid Supplementation Programs on the Performance and Breast Meat Yield Uniformity of 42-d-Old Broilers

This study aimed at evaluating four dietary L-Glutamine (L-Gln) or L-Gln plus L-Glutamate (L-Glu) supplementation programs on the performance, breast yield, and uniformity of broilers. A total of 2,112 one-d-old male Cobb 500(r) broilers were distributed according to a randomized block design in a 2 × 4 factorial arrangement (L-Gln or L-Gln plus L-Glu × 4 supplementation programs), totaling eight treatments with 12 replicates of 22 broilers each. The supplementation programs consisted of the dietary inclusion or not of 0.4% of L-Gln or L-Gln plus L-Glu for four different periods: 0 days (negative control), 9d, 21d, and 42d. Feed intake (FI, g), body weight gain (BWG, g), feed conversion ratio (FCR, kg/kg), coefficient of variation of body weight (CV, %), body weight uniformity (UNIF, %), breast weight (BW, g), breast yield (BY, %), coefficient of variation of breast weight (CVB), breast uniformity (UNIFB), coefficient of variation of breast yield (CVBY), and breast yield uniformity (UNIFBY) were evaluated. Birds fed the diets treatments supplemented with L-Gln or L-Gln plus L-Glu for 9d presented 3% higher BWG (p<0.05) compared with the controls. The L-Gln or L-Gln plus L-Glu supplementation until broilers were 21 days old resulted in 14, 10, 16, and 12% improvements (p<0.05) in CV, UNIF, CVBY, UNIFBY, respectively. The supplementation of 0.4% L-Gln (L-Gln 99%) or L-Gln plus L-Glu (minimum 95%) to pre-starter and starter broiler diets is recommended to improve body weight gain and uniformity.

Efeito da suplementação com L-glutamina livre e na forma de dipeptídeo sobre eixo glutamina-glutationa, sistema imune, sistema inflamatório e vias de sinalização proteica em camundongos submetidos à endotoxemia / Effects of dietary supplementation with L-glutamine in the free and dipeptide forms on glutamine-glutathione axis, immune system, inflammatory system and protein signaling pathwaysin mice submitted to endotoxemia

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

Suplementação de glutamina em dietas elaboradas com ingredientes de origem vegetal e animal para pintos de corte / Supplementation of glutamine in diets with ingredients from animal and vegetable sources for broiler chicks

Foi avaliado o efeito da suplementação da glutamina em dietas contendo ingredientes de origem animal sobre o desempenho e a integridade intestinal de pintos de corte, criados até 21 dias de idade. Os tratamentos constituíram-se de combinações entre tipos de dieta, com ingredientes de origem vegetal ou vegetal+animal e suplementação de glutamina (0,0; 0,5; 1,0 e 2,0%). O delineamento foi em blocos ao acaso em arranjo fatorial 2x4, tipos de ração x percentagem de glutamina, com cinco repetições e 12 pintos por unidade experimental. Não houve efeito da interação tipo de dieta versus suplementação de glutamina sobre o desempenho, e os tratamentos não influenciaram o desempenho de pintos de corte. Houve efeito quadrático da suplementação de glutamina sobre o coeficiente de digestibilidade da proteína bruta. A suplementação com glutamina aumentou altura de vilos e profundidade de cripta no duodeno. A utilização de produtos de origem animal em dietas para pintos na fase inicial não prejudica o desempenho, e a inclusão de glutamina melhora a integridade intestinal.

The effect of glutamine supplementation in diets formulated with animal by-products on the performance and integrity of the small intestine of broiler chicks up to 21 days of age was evaluated. The treatments were the combination of types of diets (only with ingredients from a vegetal source or vegetal plus animal source) and levels of glutamine (0.0; 0.5; 1.0 and 2.0%). The experimental design was randomized blocks in a 2x4 factorial scheme (kinds of diets x levels of glutamine), with five replicates and 12 birds per experimental unit. No interaction between diets and glutamine supplementation and treatment effects on the performance traits were observed during the chick starter phase. There was a quadratic effect of glutamine on the crude protein digestibility coefficient. Birds supplemented with glutamine diets showed higher villus height and crypt depth in the duodenum. Broiler diets formulated with animal ingredients have no effect on chick performance during the initial phase, and glutamine supplementation improved the small intestine integrity.

Efeito da glutamina em matrizes suínas lactantes

Objetivou-se, avaliar a influência da suplementação de L-Glutamina mais L-Glutamato nos principais componentes do leite (gordura, proteína, lactose, sólidos totais e Contagem de Células Somáticas), durante os 21 dias de lactação. Utilizou-se 30 matrizes suínas híbridas de linhagem Dalland divididas em dois tratamentos: Controle e Aminogut que receberam 1,5% de Aminogut (L-Gln + L-Glu) na ração. As fêmeas foram alojadas no galpão maternidade, em gaiolas individuais. A suplementação iniciou-se uma semana antes do parto. Nos dias 1 (dia do parto), 7 (uma semana pós-parto) e 21 (dia do desmame) foram coletadas amostras de colostro e leite com volume médio de 30 mL, coletado nas tetas peitorais. As amostras foram refrigeradas e analisadas no laboratório de leite PROGENE da UFRPE, para determinação dos valores percentuais de proteína, gordura, sólidos totais e lactose e a contagem de células somáticas (CCS). Utilizou-se delineamento inteiramente casualizado com dois tratamentos (Controle e Aminogut), todas as variáveis estudadas foram analisadas no Pacote Estatístico Statistical Analysis System – SAS, versão 8, individualmente e de suas interações. A glutamina influenciou (P<0,01) o teor de gordura, de sólidos totais e de CCS do colostro e leite de porcas. Não houve interação entre as variáveis.

Suplementação de glutamina em dietas elaboradas com ingredientes de origem vegetal e animal para pintos de corte / Supplementation of glutamine in diets with ingredients from animal and vegetable sources for broiler chicks

Foi avaliado o efeito da suplementação da glutamina em dietas contendo ingredientes de origem animal sobre o desempenho e a integridade intestinal de pintos de corte, criados até 21 dias de idade. Os tratamentos constituíram-se de combinações entre tipos de dieta, com ingredientes de origem vegetal ou vegetal+animal e suplementação de glutamina (0,0; 0,5; 1,0 e 2,0%). O delineamento foi em blocos ao acaso em arranjo fatorial 2x4, tipos de ração x percentagem de glutamina, com cinco repetições e 12 pintos por unidade experimental. Não houve efeito da interação tipo de dieta versus suplementação de glutamina sobre o desempenho, e os tratamentos não influenciaram o desempenho de pintos de corte. Houve efeito quadrático da suplementação de glutamina sobre o coeficiente de digestibilidade da proteína bruta. A suplementação com glutamina aumentou altura de vilos e profundidade de cripta no duodeno. A utilização de produtos de origem animal em dietas para pintos na fase inicial não prejudica o desempenho, e a inclusão de glutamina melhora a integridade intestinal.(AU)

The effect of glutamine supplementation in diets formulated with animal by-products on the performance and integrity of the small intestine of broiler chicks up to 21 days of age was evaluated. The treatments were the combination of types of diets (only with ingredients from a vegetal source or vegetal plus animal source) and levels of glutamine (0.0; 0.5; 1.0 and 2.0%). The experimental design was randomized blocks in a 2x4 factorial scheme (kinds of diets x levels of glutamine), with five replicates and 12 birds per experimental unit. No interaction between diets and glutamine supplementation and treatment effects on the performance traits were observed during the chick starter phase. There was a quadratic effect of glutamine on the crude protein digestibility coefficient. Birds supplemented with glutamine diets showed higher villus height and crypt depth in the duodenum. Broiler diets formulated with animal ingredients have no effect on chick performance during the initial phase, and glutamine supplementation improved the small intestine integrity.(AU)

Safety of oral glutamine in the abbreviation of preoperative fasting: a double-blind, controlled, randomized clinical trial.

INTRODUCTION: No study so far has tested a beverage containing glutamine 2 h before anesthesia in patients undergoing surgery. OBJECTIVES: The aim of the study was to investigate: 1) the safety of the abbreviation of preoperative fasting to 2 h with a carbohydrate-L-glutamine-rich drink; and 2) the residual gastric volume (RGV) measured after the induction of anesthesia for laparoscopic cholecystectomies. METHODS: Randomized controlled trial with 56 women (42 (17-65) years-old) submitted to elective laparoscopic cholecystectomy. Patients were randomized to receive either conventional preoperative fasting of 8 hours (fasted group, n = 12) or one of three different beverages drunk in the evening before surgery (400 mL) and 2 hours before the initiation of anesthesia (200 mL). The beverages were water (placebo group, n = 12), 12.5% (240 mOsm/L) maltodextrine (carbohydrate group, n = 12) or the latter in addition to 50 g (40 g in the evening drink and 10 g in the morning drink) of L-glutamine (glutamine group, n = 14). A 20 F nasogastric tube was inserted immediately after the induction of general anesthesia to aspirate and measure the RGV. RESULTS: Fifty patients completed the study. None of the patients had either regurgitation during the induction of anesthesia or postoperative complications. The median (range) of RGV was 6 (0-80) mL. The RGV was similar (p = 0.29) between glutamine group (4.5 [0-15] mL), carbohydrate group (7.0 [0-80] mL), placebo group (8.5 [0-50] mL), and fasted group (5.0 [0-50] mL). CONCLUSION: The abbreviation of preoperative fasting to 2 h with carbohydrate and L-glutamine is safe and does not increase the RGV during induction of anesthesia.

Metabolic changes induced by pre-administration of L-alanyl-glutamine and Omega-3 in Wistar rats subjected to sepsis / Alterações metabólicas induzidas pela pré-administração de L-alanil-glutamina e ômega-3 em ratos Wistar submetidos à sepse

PURPOSE: To evaluate the metabolic changes induced by pre-administration of L-alanyl-glutamine (L-Ala-Gln) and omega-3 (ω-3) in rats subjected to sepsis. METHODS: Eighteen male Wistar rats were randomized into three groups (n=6) and treated with saline (group Control-G-1), L-Ala-Gln (0.75 mg /kg , G-2) or ω-3 (0.2 g /kg, G-3 ) administered intravenously 3, 2 and 1 day and 30 minutes before induction of sepsis. Samples (blood, striated muscle and liver) were collected 48 hours after induction of sepsis, to measure the concentrations of metabolites (pyruvate, lactate, glucose and ketone bodies. RESULTS: There was a significant increase in muscle glycolysis and gluconeogenesis in the liver in rats treated with L-Ala-Gln and ω-3, compared to the control group, 48 hours after induction of sepsis. CONCLUSION: Pre-administration of L-Ala-Gln or ω-3 to rats subjected to sepsis resulted in similar metabolic changes, by rising glycolysis in peripheral tissues and stimulating hepatic gluconeogenesis and ketogenesis, resulting in increased energy supply to septic rats.(AU)

OBJETIVO: Avaliar as alterações metabólicas induzidas pela pré-administração de L-alanil-glutamina (L-Ala-Gln) e ômega-3 (ω-3) em ratos Wistar submetidos à sepse. MÉTODOS: Dezoito ratos machos Wistar, randomizados em três grupos iguais (n=6) e tratados com solução salina (grupo Controle-G-1), L-Ala-Gln (0,75mg/Kg) ou ω-3 (0,2g/Kg) por via endovenosa administrados 3, 2 e 1 dia e 30 minutos antes da indução do estado de sepse. Amostras (sangue, músculo estriado e fígado) foram coletadas 48 horas após indução da sepse, para dosagem das concentrações de metabólitos (piruvato, lactato, glicose e corpos cetônicos). RESULTADOS: Houve aumento significante da glicólise no músculo e da gliconeogênese no fígado nos ratos tratados com L-Ala-Gln e ω-3, comparados ao controle, 48 horas após a indução da sepse. CONCLUSÃO: A pré-administração de L-Ala-Gln ou ω-3 em ratos submetidos à sepse resultou em alterações metabólicas semelhantes, com aumento da glicólise nos tecidos periféricos e da gliconeogênese hepática e cetogênese, aumentando a oferta de energia disponível.(AU)

The safety of oral use of L-glutamine in middle-aged and elderly individuals.

OBJECTIVE: To evaluate the safety of nutraceutical oral administration of L-glutamine (L-Gln) in middle-aged and elderly individuals. METHODS: In this randomized, crossover, double-blind clinical study, 30 residents of a long-term-care institution, selected according to a modified SENIEUR protocol (Working Party of the EURAGE Concerted Action Programme on Ageing of the European Community), were studied. Fourteen subjects received orally 0.5 g kg(-1) d(-1) of L-Gln and 16 received calcium caseinate for 14 d, followed by a 5-d washout. Supplements were switched for the second 14-d trial. Laboratory tests for hepatic and renal functions and ammonemia were performed and the estimated glomerular filtration rate (eGFR) was calculated. RESULTS: Of the 30 subjects, 16 were men, mean age was 69+/-8.8 y, average weight was 61.8+/-14.2 kg, and mean serum albumin was 4.0+/-0.3g/dL. Neither adverse clinical effects nor clinically significant laboratory changes were noted during L-Gln supplementation. There was no difference in ammonemia between the groups. There were statistically but not clinically significant increases in plasma urea nitrogen and creatinine concentrations. There was no significant decrease in eGFR during calcium caseinate supplementation (-2.9%). The eGFR decreased significantly after L-Gln supplementation (-13.3%) but well below the 25% limit for biologic significance. CONCLUSION: Increases in serum urea nitrogen and creatinine and decrease in eGFR are probably due to difficulties by older kidneys in metabolizing the supplemented protein sources. Although not clinically significant, those alterations impose a rigorous control on the evaluation parameters of renal function during oral L-Gln supplementation, with doses of 0.5 g kg(-1) d(-1) in middle-aged and elderly individuals.

Nutrição enteral precoce com glutamina em cães com gastrenterite hemorrágica pelo parvovirus canino / Early enteral nutrition with glutamine in dogs with hemorrhagic gastroenteritis by canine parvovirus

The effect of the addition of glutamine aminoacid in a solution to early enteral nutrition in dogs with hemorrhagic gastroenteritis by parvovirus (GEHV) was evaluated in a prospective study with 20 dogs. The animals were randomly separated in two groups of treatment. Animals in group 1 did not receive glutamine and in group 2 received glutamine by enteral solution. The mortality rate was 20% in group 1 and 10% in group 2, but difference was not statistically significative. The addition of glutamine in a solution to enteral nutrition did not change mortality rate.