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

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2014-05, Vol.30 (5), p.602-611
• Main Authors: Cruzat, Vinicius Fernandes, Ph.D, Bittencourt, Aline, B.Ph.Ed, Scomazzon, Sofia Pizzato, B.Biomed, Leite, Jaqueline Santos Moreira, B.Nutr, de Bittencourt, Paulo Ivo Homem, Ph.D, Tirapegui, Julio, Ph.D
• Format: Article
• Language: English
• Subjects: Amino acids; Animal bacterial diseases; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Bacterial diseases; Biological and medical sciences; Cytokines; Dietary Supplements; Dipeptides - pharmacology; Dipeptides - therapeutic use; Endotoxemia - complications; Endotoxemia - drug therapy; Endotoxemia - microbiology; Escherichia coli Infections - complications; Escherichia coli Infections - drug therapy; Escherichia coli Infections - microbiology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Glutamine - metabolism; Glutamine - pharmacology; Glutamine - therapeutic use; Glutathione - metabolism; Infectious diseases; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Inflammation Mediators - metabolism; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1 Receptor-Associated Kinases - metabolism; l-alanine; Lipopolysaccharides; Liver - metabolism; Lymphocytes; Lymphocytes - metabolism; Male; Medical sciences; Mice; Mice, Inbred Strains; Muscle, Skeletal - metabolism; Musculoskeletal system; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Nuclear factor-κB; Oxidative stress; Oxidative Stress - drug effects; Proteins; RNA, Messenger - metabolism; Sepsis; Thiobarbituric Acid Reactive Substances; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2013.10.019

Abstract 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.