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

Stefania Marzocco, Rosanna Di Paola, Giuseppina Autore, Emanuela Mazzon, Aldo Pinto, Achille P. Caputi, Cristoph Thiemermann, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)38-44
Number of pages7
JournalShock
Volume21
Issue number1
Publication statusPublished - Jan 2004

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

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    Marzocco, S., Di Paola, R., Autore, G., Mazzon, E., Pinto, A., Caputi, A. P., Thiemermann, C., & Cuzzocrea, S. (2004). Calpain inhibitor I reduces intestinal ischemia-reperfusion injury in the rat. Shock, 21(1), 38-44.