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

Abstract

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.

• Authors: Stefania Marzocco, Rosanna Di Paola, Giuseppina Autore, Emanuela Mazzon, Aldo Pinto, Achille P Caputi, Cristoph Thiemermann, Salvatore Cuzzocrea
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 21 Issue 1 Pg. 38-44 (Jan 2004) ISSN: 1073-2322 [Print] United States
• PMID: 14676682 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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, metabolism)