Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise

Br J Nutr. 2016 Aug;116(3):470-9. doi: 10.1017/S0007114516001999. Epub 2016 May 24.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / pharmacology*
  • Alanine / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Creatine Kinase / blood
  • Cytokines / blood
  • Dietary Supplements*
  • Dipeptides / pharmacology*
  • Dipeptides / therapeutic use
  • Glutamine / blood
  • Glutamine / metabolism
  • Glutamine / pharmacology*
  • Glutamine / therapeutic use
  • HSP70 Heat-Shock Proteins / metabolism
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism
  • L-Lactate Dehydrogenase / blood
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • NF-kappa B / metabolism
  • Rats, Wistar
  • Resistance Training / adverse effects*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Dipeptides
  • HSP70 Heat-Shock Proteins
  • NF-kappa B
  • Glutamine
  • L-Lactate Dehydrogenase
  • Creatine Kinase
  • Alanine
  • alanylglutamine