• Vinicius Fernandes Cruzat, Aline Bittencourt, Sofia Pizzato Scomazzon, Jaqueline Santos Moreira Leite, Paulo Ivo Homem de Bittencourt, and Julio Tirapegui.
• Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Perth, Western Australia. Electronic address: Vinifc@usp.br.
• Nutrition. 2014 May 1; 30 (5): 602-11.

ObjectiveThe 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.MethodsB6.129 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.ResultsEndotoxemia 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 β, 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/β. 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).ConclusionOral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.Copyright © 2014 Elsevier Inc. All rights reserved.

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