The major functions of glutathione S-transferase (Glutathione S-transferase; GST) include the maintenance of intracellular redox state of substances, and detoxification of cells of endogenous and exogenous toxic substances, and therefore GST plays an important physiological role. The main purpose of this study is to find the effects of SjGST and morin on human breast cancer cell on growth and migration , and the possible mechanisms. Therefore we first carried out cell proliferation assays in vitro . Results showed that at low concentrations of SjGST could enhance the proliferation of breast cancer cell line MDA-MB435s better then high concentrations.And the cell migration assays results showen, when 36 and 48 hours that the low concentration SjGST can enhance the breast cancer cell line MDA-MB435s migration. Morin have antioxidant,anti-free radicals, and inhibitor of cancer cells growth. Therefore, we aimed at revealing the effect of more, GST and the mixture of both on growth and detoxination of MDA-MB435s. However, the results of detoxification assays shown,even add SjGST first or last or both mixed ,the concentration 5¡B10¡B50¡B100¡B200¡B500nM of SjGST still not protect the breast cancer cells (MDA-MB-435s cells line) to break away from morin .

No description available.

Con el fin de mejorar la producción in vitro de embriones (PIVE) desde ovocitos de cabra perpúber, fueron diseñados tres estudios en esta investigación. El objetivo del primer estudio fue determinar en ovocitos seleccionados mediante el test azul de cresol brillante (BCB), el efecto de la adición de gutatión (GSH) solo o en combinación con glucosa al medio de cultivo in vitro (CIV), sobre el desarrollo embrionario de ovocitos de cabra perpúber. Los ovocitos fueron expuestos al test de BCB y fueron clasificados como: ovocitos con citoplasma azul (BCB+) y ovocitos sin el citoplasma azul (BCB-). Los ovocitos BCB+ mostraron mayor porcentaje de maduración nuclear que los ovocitos BCB- y grupo control (82.6%, 55.7% y 74.7% respectivamente). El porcentaje de ovocitos poliespérmicos fue mayor en ovocitos BCB- que en los BCB+. La suplementación del medio de cultivo (CIV) con 1 mM de GSH, no afectó el desarrollo embrionario, pero el porcentaje de embriones totales desarrollados después del cultivo fue mayor en ovocitos BCB+ que en los BCB-, independientemente de la suplementación con GSH. La adición de glucosa, sola o con GSH no afectó el desarrollo embrionario. La finalidad del segundo estudio era evaluar el efecto de agregar diferentes concentraciones de cisteamina (100μM, 200μM o 400μM) al medio de MIV y al medio de CIV (50 μM o 100 μM) sobre el desarrollo embrionario de ovocitos de cabra perpúber seleccionados por el test BCB. La adición de 400 μM de cisteamina al medio MIV mejoró la fecundación normal y desarrollo embrionario de ovocitos BCB- a los mismos niveles de los ovocitos BCB+. Las proporciones de mórulas mas blastocistos desarrollados no fueron afectados por los tratamientos. Finalmente, fue estudiado el efecto de la adición de cisteamina (400 μM) para el medio de MIV, glutatión (1mM) al medio FIV e ionomicina al medio de capacitación espermática. Este tratamiento mejoró la fecundación normal, cigotos con pronúcleos masculinos y el desarrollo embrionario de ovocitos de cabra prepuber, sin embargo no mejoró el desarrollo de blastocistos. / With the aim of trying to improve in vitro embryo production (IVEP) from prepubertal goat oocytes, three studies were designed in this investigation. The objetive of first study was to assess, in oocytes selected by the brillant cresyl blue (BCB) test, the effect of the addition to in vitro culture (IVC) medium of either glutathione (GSH) alone or GSH in combination with glucose on the embryo development. Oocytes were exposed to BCB and were classified as: oocytes with a blue cytoplasm (BCB+) and oocytes without blue cytoplasm (BCB-). BCB+ oocytes showed higher percentage of nuclear maturation than the BCB- and control group (82.6%, 55.7% and 74.7%, respectively). The percentage of polyspermic oocytes was higher in BCB- than BCB+ oocytes. Supplementation of in vitro culture (IVC) medium with 1mM de GSH did not affect embryo development, but the porcentage of total embryos developed after culture was higher in BCB+ oocytes than in BCB- oocytes independently of the GSH supplementation. The addition of glucose, alone or with GSH, did not affect embryo development. The aim of the second study was to evaluate the effect of adding different concentrations (100μM, 200μM and 400 μM) of cyteamine to the IVM medium and to the in vitro embryo culture (IVC) medium (50 μM or 100 μM) on the embryo development of prepubertal goat oocytes BCB-selected. The addition of 400 μM cysteamine to the IVM improved normal fertilisation and embryo development of BCB- oocytes at the same rates as those obtained from BCB+ oocytes. The proportions of morulae plus blastocyst development were not affects by the treatments. Finally, was studied the effect of adding cysteamine (400 μM) to IVM medium, glutathione (1mM) to IVF medium and ionomycin to the sperm capacitation medium. This treatment improved normal fertilisation, zygotes with male pronucleus and embryo development of prepubertal goat oocytes, however did not improve blastocyst development.

Ovarian toxicants 4-vinylcychlohexene (VCH) and 7,12-dimethylbenz[a]anthracene (DMBA) requires bioactivation to induce follicle loss. VCH is bioactivated to monoepoxides (1,2-VCM and 7,8-VCM), and subsequently to an ovotoxic diepoxide (VCD) by hepatic CYP 2A and CYP 2B. DMBA is sequentially bioactivated to the ovotoxicant DMBA-3,4-diol-1,2-epoxide by hepatic CYP 1B1, microsomal epoxide hydrolase (mEH), and CYP 1A1/1B1 enzymes. Even though the liver is the primary organ metabolizing VCH and DMBA to reactive intermediates, several studies suggest that the ovary can also metabolize these two compounds. Studies were designed to investigate the role of ovarian metabolism in the resulting ovotoxicity of these two compounds using a novel mouse ovarian culture system. The hypothesis was that the ovary can participate in bioactivation and detoxification of VCH/VCM and DMBA and thereby influence the resulting ovotoxicity.Postnatal day 4 CYP 2E1 wild-type, null and B6C3F1 mouse ovaries were incubated with 1,2-VCM, VCD or DMBA for various lengths of time. 28 day old female CYP 2E1 wild-type and null mice were dosed (15d, i.p) with VCH, 1,2-VCM, VCD, or sesame oil (control). Following incubations and dosing, ovaries were prepared for histological evaluation of follicle numbers, mEH mRNA level, or mEH protein level. Medium from cultures were analyzed by LC/MS for VCD-GSH adducts.DMBA was found to be a potent ovotoxicant compared to VCH/VCM/VCD. In the ovarian culture system, VCM-induced toxicity required the CYP 2E1 enzyme. However, in vivo dosing studies indicated that in the presence of hepatic metabolism the ovary plays a minimal role in VCH/VCM-induced toxicity. Studies utilizing LC/MS showed that once bioactivated to VCD, this ovotoxic metabolite can be detoxified by glutathione conjugation in the ovary. Follicle loss induced by the ovotoxicant DMBA was found to involve mEH enzyme in culture.Collectively, these studies show that the ovary has the capacity to bioactivate and detoxify ovotoxicants. In the presence of hepatic metabolism ovarian effects might play only a minimal role in the resulting toxicity. The role of ovarian metabolism in the whole animal needs to be further investigated, especially for potent toxicants such as DMBA that can induce ovotoxicity at nanomolar concentrations.

PURPOSE: The Nrf2/Keap1/ARE pathway is a major regulator of cytoprotective responses to oxidants. Gluatredoxin-1 (Glrx-1), a small thiol transferase removes glutathione (GSH) adducts from proteins and participates in redox signaling. Glrx-/- mice exhibit increased protein GSH adducts (PSSG) and non-alcoholic fatty liver disease (NAFLD). Unexpectedly, our Glrx-/- mice showed increased hepatic glutathione (GSH) levels. The Nrf2/Keap1/ARE pathway, as an important regulator of glutathione synthesis, could be regulated by Glrx-1 activity. METHODS: To determine the role of Nrf2 in vivo, we treated Glrx-/- mice with high fat high sucrose (HFHS) diet to induce metabolic and oxidative stress. Livers were harvested at 10 months of age after 8 months on HFHS diet. Gene expression of Nrf2 and its down-signaling targets were determined using RT-qPCR and protein expression was accessed via WB. To determine the role of Nrf2 in Glrx-deficiency in vitro, Glrx siRNA was transfected in HEK293A and HepG2 cells and exposed to high palmitate high glucose (HPHG) to mimic metabolic stress and hydrogen peroxide to mimic oxidative stress. RESULTS: Glrx-/- deficiency increased Nrf2 activity and gene expression, and decreased Keap1 activity and gene expression. Glrx silencing in liver promoted Nrf2 activity and translocation to the nucleus, and downstream targets of Nrf2 were upregulated. CONCLUSION: Our findings indicate that the Nrf2/Keap1/ARE pathway is regulated by Glrx in vitro and in vivo.

O cluster Drosophila buzzatii (grupo D. repleta) é constituído por sete espécies crípticas, com desenvolvimento larval ocorrendo exclusivamente em tecidos de cactos em decomposição. Os cactos são constituídos por diversos compostos químicos, que incluem substâncias tóxicas (alcaloides, esteroides e fenóis) para insetos. Nas espécies cactofílicas Drosophila mojavensis e D. buzzatii, o gene GSTD1, da família Glutationa S- transferases, é superexpresso em larvas submetidas a substratos tóxicos. GSTD1 é indicado com função de desintoxicação, sendo importante alvo de seleção e necessário no processo de adaptação em espécies de Drosophila. No presente trabalho, foram isoladas regiões codificadoras completas do gene GSTD1 das sete espécies do cluster D. buzzatii com o objetivo de entender a evolução nas sequências de DNA e nos fenótipos (proteínas), com análise da estrutura e função da proteína GSTD1, no processo de desintoxicação, entre as espécies do cluster. Foram sequenciados 630 pb do gene GSTD1 para cada espécie e a estrutura primária da proteína, composta por 209 resíduos de aminoácidos, foi inferida \"In silico\". Nas inferências filogenéticas Bayesiana com o gene GSTD1, é indicado monofilietismo do cluster, com formação do primeiro aglomerado para D. buzzatii e D. koepferae, o segundo composto por D. antonietae e D. serido e, por último, um agrupamento entre D. gouveai, D. borborema e D. seriema. Sinais de seleção positiva nas sequências de DNA resultam em alterações nos resíduos de aminoácidos nas posições 39, 133, 136 e 209, com mudanças na estrutura química da proteína GSTD1, entre as espécies do cluster. Foram obtidos sete modelos da proteína GSTD1, realizada com modelagem por homologia, uma para cada espécie do cluster D. buzzatii. No docking molecular, entre as proteínas GSTD1 com o ligante mescalina, foi observado que as proteínas de D. seriema, D. gouveai e D. koepferae apresentaram melhores interações químicas com o ligante e menor gasto energético. O ligante mescalina foi posicionado entre duas regiões GSH (glutationa redutase) em D. seriema, D. gouveai e D. koepferae. A evolução do gene GSTD1 entre as espécies do cluster D. buzzatii envolve sinais de seleção positiva em sequências de DNA com mudanças químicas em resíduos de aminoácidos no sítios-G e na estrutura interna da proteína GSTD1, bem como a capacidade do sítio de ligação GSH reconhecer o composto alcaloide. / The cluster Drosophila buzzatii (group D. repleta) is constituted by seven cryptic species, with larval development occurring exclusively in tissues of decomposing cacti. Cacti are composed of several chemical compounds, which include toxic substances (alkaloids, steroids and phenols) for insects. In the cactophilic species Drosophila mojavensis and D. buzzatii, the GSTD1 gene, from the Glutathione S-transferases family, is overexpressed in larvae submitted to toxic substrates. GSTD1 is indicated with detoxification function, being important target of selection and necessary in the adaptation process in Drosophila species. In the present work, complete coding regions of the GSTD1 gene were isolated from the seven species of the D. buzzatii cluster with the objective of understanding the evolution in DNA sequences and phenotypes (proteins), with analysis of the structure and function of the GSTD1 protein in the process detoxification, among the species of the cluster. 630 bp of the GSTD1 gene was sequenced for each species and the primary structure of the protein, composed of 209 amino acids, was inferred \"In silico\". In the Bayesian phylogenetic inferences with the GSTD1 gene, monophyly of the cluster is indicated, with the formation of the first grouping between D. buzzatii and D. koepferae, the second composed by D. antonietae and D. serido and finally, a grouping between D. gouveai, D. borborema and D. seriema. Signs of positive selection on DNA sequences result in changes in amino acid residues at positions 39, 133, 136 and 209, with changes in the chemical structure of the GSTD1 protein among the species in the cluster. We obtained seven models of the GSTD1 protein, performed with homology modeling, one for each species of the D. buzzatii cluster. In the molecular docking between the GSTD1 proteins with the mescaline ligand, it was observed that the proteins of D. seriema, D. gouveai and D. koepferae presented better chemical interactions with the ligand and lower energy expenditure. Interestingly, the mescaline linker was positioned between two GSH (glutathione reductase) regions, in D. seriema, D. gouveai and D. koepferae. The evolution of the GSTD1 gene among D. buzzatii cluster species involves positive selection signals in DNA sequences with chemical changes in amino acid residues at the G-sites and in the internal structure of the GSTD1 protein, as well as the ability of the GSH binding site to recognize the alkaloid compound.

A glutamina é o aminoácido livre mais abundante no plasma e músculo, sendo utilizada em elevadas taxas por diversas células na manutenção e promoção de funções essenciais à homeostasia celular. Entretanto, em algumas situações catabólicas, entre as quais exercícios físicos intensos e prolongados ou exaustivos é observada a redução na concentração de glutamina, o que pode comprometer as funções celulares. A suplementação com dipeptídeos de glutamina, tais como a L-alanil-L-glutamina (DIP) pode representar um eficiente meio de fornecimento de glutamina por via oral para o organismo. Desta forma, ratos Wistar machos foram treinados e suplementados com o DIP (1,49 g•kg-1) ou uma solução contendo os aminoácidos L-glutamina (1 g•kg-1) e L-alanina (0,61 g•kg-1) livres (GLN+ALA) ou água (CON), sendo sacrificados em dois tempos, antes (TR) e após (INT) um exercício intenso de natação. No plasma, a concentração de glutamina, glutamato, glicose, amônia, CK, LDH, TNF-α e PgE2 foram avaliadas. No músculo sóleo e gastrocnêmio e no fígado foram determinadas as concentrações de glutamina, glutamato, GSH, GSSG e proteínas totais. Antes do exercício intenso, ambas as suplementações atenuaram a liberação de CK no plasma. O grupo DIP-TR apresentou maior concentração de glutamato, GSH e GSH/GSSG no sóleo e fígado. Maior concentração de glutamina, glutamato, GSH ou GSH/GSSG foi observada no sóleo e fígado do grupo GLN+ALA-TR. Após o exercício intenso, ambas as suplementações atenuaram a liberação de amônia e TNF-α, e no grupo DIP-INT menor concentração de PgE2 foi observada. Maior concentração de glutamina, glutamato e GSH/GSSG no sóleo e glutamato no gastrocnêmio foram encontrados nos grupos DIP-INT e GLN+ALA-INT. No fígado foi encontrada também maior concentração de GSH e GSH/GSSG, decorrentes das suplementações. Os nossos resultados levam à conclusão de que a suplementação oral com L-glutamina e L-alanina na forma livre ou como dipeptídeo, L-alanil-L-glutamina, pode aumentar os estoques musculares e hepáticos de GSH e alterar o estado redox celular, atenuando lesão e a inflamação induzidas pelo exercício físico. / Glutamine is the most abundant free amino acid found in plasma and muscle, and is utilized at high rates by many cells for maintenance and promotion of cell function. However, in some catabolic situations, like intense and prolonged or exhaustive physical exercise, a reduction in GLN availability is observed, fact that may impair the cell functions. Oral supplementation with dipeptides of glutamine, like L-alanyl-L-glutamine may serve as an interesting way to deliver glutamine to the organism. Male Wistar rats were trained and supplemented with DIP (1,49 g•kg-1) or mixture containing free L-glutamine (1 g&#8226kg-1) and Lalanine (0,61 g•kg-1) or water (CON) and sacrificed in distinct times: before (TR) and immediately after (INT) intense exercise of swim. Plasma and serum concentrations of glucose, GLN, glutamate, ammonia, CK, LDH, TNF-• and PgE2 were evaluated. In muscles (soleus and gastrocnemius) and liver GLN, glutamate, GSH, GSSG and total proteins also were evaluated. Low concentration of CK in plasma was observed in both supplemented groups before the exhaustive test. The DIP-TR presented more concentration of glutamate, GSH e GSH/GSSG in the soleus muscle and liver. Higher concentration of glutamine, glutamate and GSH/GSSG was seen in GLN+ALATR group. Both groups supplemented with DIP and GLN+ALA after the exhaustive test, exhibit decreases in ammonia and TNF-α, and the group DIP-INT, demonstrated decrease in PgE2. Glutamine, glutamate and GSH/GSSG increases in the soleus and glutamate in the gastrocnemius increases in groups DIP-INT and GLN+ALA-INT. Increases in GSH and GSH/GSSG in liver were found in the same groups, compared to CON-INT. Our results indicate that oral supplementation with free L-glutamine added to L-alanine or the dipeptide, Lalanyl-L-glutamine, may influence the muscle and liver stores of GSH and the cellular redox state, and this may attenuate damage and inflammation induced by severe physical exercise.

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-&#945;, IL-6, IL-1&#946; e IL-10 foi atenuada pelas suplementações, bem como a expressão de mRNAs envolvidos com a resposta inflamatória, ativadas pela via do NF-&#954;B(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-&#945;, IL-6, IL-1&#946; and IL-10 were attenuated by supplementation as well as the expression of mRNAs involved in the inflammatory response, activated by NF&#954;-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.

Buvo nustatyta, kad redukuoto glutationo koncentraciją pelių kepenyse kadmis padidino po 8 val. 35 proc., o po 14 dienų sumažino 35 proc. Po 8 val., tiek cinkas, tiek selenas taip pat padidino redukuoto glutationo koncentraciją, atitinkamai, 27 proc. ir 17 proc. Įvertinant malondialdehido koncentraciją pelių kepenyse, buvo nustatyta, kad kadmis padidino malondialdehido koncentraciją po 8, 24 val. ir 14 dienų, atitinkamai, 336 proc., 218 proc. ir 182 proc. Veikiant cinkui ir selenui, malondialdehido koncentracija pelių kepenyse padidėjo po 24 val. ir 14 dienų, atitinkamai, 325 proc. ir 437 proc., o po 14 dienų, atitinkamai, 162 proc. ir 288 proc. Taigi, cinkas pajėgus apsaugoti redukuotą glutationą nuo oksidacijos tik 8 val., o po ilgesnio laiko redukuotas glutationas išeikvojamas. Po 8 ir 24 val. tiek cinkas, tiek selenas pelių kepenyse geba apsaugoti lipidus nuo peroksidacijos, o po 14 dienų redukuotą glutationą nuo oksidacijos ir lipidus nuo peroksidacijos apsaugo tik žaliosios arbatos ekstraktas. / It was determined, that after 8 h cadmium increased glutathione concentration by 35 % while after 14 days decreased by 35 %. After 8 h both zinc and selenium also increased reduced glutathione concentration, respectively, 27 % and 17 %. Evaluating malondialdehyde concentration in mice liver, it was established, that cadmium increased malondialdehyde concentration after 8, 24 h and 14 days, respectively, 336 %, 218 % and 182 %. When mice liver were affected with zinc and selenium, malondialdehyde concentration increased after 24 h, respectively, 325 % and 437 % and after 14 days, respectively, 162 % and 288 %. To sum up, zinc can protect reduced glutathione from oxidation in mice liver just for 8 h, and after a longer period reduced glutathione is depleted. After 8, 24 h and 14 days both, zinc and selenium are eager to protect liver from lipid peroxidation and after 14 days reduced glutathione from oxidation. Lipids from peroxidation process can protect only green tea extract.

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-&#945;, IL-6, IL-1&#946; e IL-10 foi atenuada pelas suplementações, bem como a expressão de mRNAs envolvidos com a resposta inflamatória, ativadas pela via do NF-&#954;B(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-&#945;, IL-6, IL-1&#946; and IL-10 were attenuated by supplementation as well as the expression of mRNAs involved in the inflammatory response, activated by NF&#954;-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.