Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia

Vinicius Fernandes Cruzat, Aline Bittencourt, Sofia Pizzato Scomazzon, Jaqueline Santos Moreira Leite, Paulo Ivo Homem De Bittencourt, Julio Tirapegui

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76 Citations (Scopus)


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 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). Conclusion: Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.

Original languageEnglish
Pages (from-to)602-611
Number of pages10
Issue number5
Publication statusPublished - 1 Jan 2014
Externally publishedYes


  • Amino acids
  • Antioxidants
  • Cytokines
  • L-alanine
  • Nuclear factor-κB
  • Sepsis


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