Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury.

Abstract

BACKGROUND:

Adenosine attenuates skeletal muscle reperfusion injury, but its short half-life in vivo limits potential therapeutic benefits. The aim of this study was to ascertain whether inosine, a stable adenosine metabolite, modulates skeletal muscle reperfusion injury.

MATERIALS AND METHODS:

C57BL/6 mice were randomized (8-10 per group) to six groups: time controls; inosine (100 mg/kg) before anesthesia; 2 h of bilateral tourniquet hindlimb ischemia; I/R (2 h of bilateral tourniquet hindlimb ischemia, 3 h of reperfusion); inosine (100 mg/kg) before I/R; drug vehicle before I/R. Serum tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 were measured before ischemia and at the end of reperfusion. Tissue edema was determined by wet/dry weight ratios. Tissue leucosequestration was assessed by the myeloperoxidase (MPO) content.

RESULTS:

At the end of reperfusion, inosine pretreatment resulted in lower MPO levels in muscle (P = 0.02) and lung (P = 0.0002) than saline pretreatment. Similarly, muscle (P = 0.04) and lung (P = 0.02) wet/dry ratios were significantly reduced with inosine but not with saline pretreatment. At the end of reperfusion, serum proinflammatory cytokine levels (TNF-alpha and MIP-2) were significantly reduced (P < 0.05) compared to preischemia levels following inosine pretreatment but not saline pretreatment. Ischemia alone did not alter any of the parameters assessed.

CONCLUSIONS:

These findings demonstrate that pretreatment with inosine attenuates the local and systemic proinflammatory responses associated with skeletal muscle reperfusion injury.

• Authors: A Wakai, D C Winter, J T Street, R G O'Sullivan, J H Wang, H P Redmond
• Journal: The Journal of surgical research (J Surg Res) Vol. 99 Issue 2 Pg. 311-5 (Aug 2001) ISSN: 0022-4804 [Print] United States
• PMID: 11469903 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Chemokine CXCL2
• Chemokines
• Cxcl2 protein, mouse
• Tumor Necrosis Factor-alpha
• Inosine
• Peroxidase

Topics

• Animals
• Chemokine CXCL2
• Chemokines (blood)
• Disease Models, Animal
• Edema (drug therapy, metabolism)
• Inosine (pharmacology)
• Lung (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal (blood supply, metabolism)
• Oxidative Stress
• Peroxidase (analysis)
• Pulmonary Edema (metabolism)
• Reperfusion Injury (drug therapy, metabolism)
• Tourniquets (adverse effects)
• Tumor Necrosis Factor-alpha (metabolism)