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

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.