Calpain inhibitor I reduces intestinal ischemia-reperfusion injury in the rat

Shock. 2004 Jan;21(1):38-44. doi: 10.1097/01.shk.0000095056.62263.b2.


In this study we evaluated the effect of calpain inhibitor I on splanchnic artery occlusion (SAO) shock-mediated injury. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure. Western blot analysis of ileum revealed a marked decrease in of IkappaB-alpha expression, and immunohistochemical examination of necrotic ileum demonstrated a marked increase in the immunoreactivity to P-selectin, intracellular adhesion molecule (ICAM-1), nitrotyrosine formation, and nuclear enzyme poly[adenosine diphosphate (ADP)-ribose] synthase (PARS) activation. An increase in myeloperoxidase activity (143 +/- 22 4.5 U/100 mg wet tissue vs. 4.5 +/- 2.5 U/100 mg wet tissue of sham-operated rats) and in malondialdehyde levels (13.12 +/- 1.2 micromol/100 mg wet tissue vs. 3.9 +/- 1.1 micromol/100 mg wet tissue of sham-operated rats) was also observed in rats subjected to ischemia-reperfusion injury. Calpain inhibitor I, given intraperitoneally 30 min before ischemia at a dose of 15 mg/kg, significantly improved mean arterial blood pressure, markedly reduced IkappaB-alpha degradation and the intensity of P-selectin and ICAM-1 in the reperfused ileum. Calpain inhibitor I also significantly prevented neutrophil infiltration (32.95 +/- 9.82 U/100 mg wet tissue), reduced malondialdehyde levels (6.76 +/- 0.98 micromol/100 mg wet tissue) and markedly improved the histological status of the reperfused tissue. In conclusion, this study demonstrates that calpain inhibitor I exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock and suggests that calpain inhibitor I may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury.

MeSH terms

  • Animals
  • Blood Pressure
  • Blotting, Western
  • Cysteine Proteinase Inhibitors / pharmacology
  • Glycoproteins / pharmacology*
  • I-kappa B Proteins / metabolism
  • Ileum / metabolism
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / metabolism
  • NF-KappaB Inhibitor alpha
  • Neutrophils / pathology
  • P-Selectin / metabolism
  • Peroxidase / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Shock*
  • Splanchnic Circulation
  • Time Factors
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism


  • Cysteine Proteinase Inhibitors
  • Glycoproteins
  • I-kappa B Proteins
  • Nfkbia protein, rat
  • P-Selectin
  • calpain inhibitors
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • 3-nitrotyrosine
  • Tyrosine
  • Malondialdehyde
  • Peroxidase
  • Poly(ADP-ribose) Polymerases