Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury

JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1122-1130. doi: 10.1177/0148607115587949. Epub 2015 Jun 9.

Abstract

Background: This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury.

Methods: There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5-oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion.

Results: IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)-6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR-induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL-6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult.

Conclusions: A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.

Keywords: adhesion molecule; glutamine; hind limb; inflammatory mediator; ischemia reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / blood
  • Cytokines / genetics
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glutamine / pharmacology*
  • Hindlimb / drug effects*
  • Hindlimb / metabolism
  • Inflammation / drug therapy*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Neutrophils / metabolism
  • Reperfusion Injury / drug therapy*

Substances

  • Cytokines
  • Glutamine