期刊
NUTRITION
卷 30, 期 5, 页码 602-611出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nut.2013.10.019
关键词
Sepsis; Nuclear factor-kappa B; Cytokines; Antioxidants; L-alanine; Amino acids
资金
- Sao Paulo State Foundation for Research Support (FAPESP) [09/52853-1]
- Brazilian National Council for Scientific and Technological Development (CNPq)/Brazilian Ministry of Science and Technology/Brazilian Ministry of Health (CNPq/MCT/CT-Saude) [551097/2007, 551097/2008, 573747/2008, 573747/2007, 573747/2006, 573747/2005, 573747/2004, 573747/2003, 563870/2010, 563870/2009]
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) F-2/j mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS1, 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 (TSARS), and nuclear factor (NF)-kappa B-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-a, interleukin (IL)-6, IL-1 beta, 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-kappa B pathway, with the phosphorylation of I kappa B kinase-alpha/3. 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. (C) 2014 Elsevier Inc. All rights reserved.
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