title: Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.
abstract: We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1β, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1β, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.
authors.affiliation: 1Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences,University of São Paulo,São Paulo,SP 05508-000,Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Raizel
authors.affiliation: 1Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences,University of São Paulo,São Paulo,SP 05508-000,Brazil.
authors.forename: Jaqueline Santos Moreira
authors.initials: JS
authors.lastname: Leite
authors.affiliation: 1Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences,University of São Paulo,São Paulo,SP 05508-000,Brazil.
authors.forename: Thaís Menezes
authors.initials: TM
authors.lastname: Hypólito
authors.affiliation: 1Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences,University of São Paulo,São Paulo,SP 05508-000,Brazil.
authors.forename: Audrey Yule
authors.initials: AY
authors.lastname: Coqueiro
authors.affiliation: 2School of Biomedical Sciences, Faculty of Health Sciences andCurtin Health Innovation Research Institute,Curtin University,WA 6102,Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Newsholme
authors.affiliation: 2School of Biomedical Sciences, Faculty of Health Sciences andCurtin Health Innovation Research Institute,Curtin University,WA 6102,Australia.
authors.forename: Vinicius Fernandes
authors.initials: VF
authors.lastname: Cruzat
authors.affiliation: 1Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences,University of São Paulo,São Paulo,SP 05508-000,Brazil.
authors.forename: Julio
authors.initials: J
authors.lastname: Tirapegui
mesh_terms: D000409:Alanine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000097:blood; D019587:Dietary Supplements; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D005973:Glutamine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017208:Rats, Wistar; D055070:Resistance Training / Q000009:adverse effects*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004151:Dipeptides; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D005973:Glutamine; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D000409:Alanine; C054122:alanylglutamine
keywords: ALA trained supplemented with l-alanine; Alanine; CK creatine kinase; CTRL trained control group; DIP dipeptide l-alanyl-l-glutamine; EDL 
                    extensor digitorum longus; GLN+ALA 
                    l-alanine plus l-glutamine; HSP heat-shock protein; Heat-shock protein; Inflammation; LDH lactate dehydrogenase; MCP-1 monocyte chemoattractant protein-1; PBMC peripheral blood mononuclear cells; RE resistance exercise; Resistance exercise; SED sedentary group; l-Alanyl-l-glutamine