In this study, we evaluated the effect of
tyrphostin AG126, a
tyrosine kinase inhibitor, in the 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. Ileum analysis revealed that SAO
shock is characterized by a significant (P<0.01) induction in
TNF-alpha and
IL-1 ileum levels, while immunohistochemistry examination of necrotic ileum demonstrated a marked increase in the immunoreactivity in intracellular adhesion molecule (ICAM-1) and
nitrotyrosine formation. A significant increase in
myeloperoxidase activity (P<0.01) was also observed in rats subjected to
ischemia-reperfusion injury.
Tyrphostin AG126, given intraperitoneally 30 min before
ischemia at the dose of 5 mg/kg, significantly improved mean arterial blood pressure, markedly reduced
TNF-alpha and IL-1beta levels and the positive staining of
ICAM-1 into the reperfused ileum.
Tyrphostin AG126 significantly improved the histological status of the reperfused tissue. In conclusion, this study demonstrates that
tyrphostin AG126 exerts multiple protective effects in splanchnic artery occlusion/reperfusion
shock and suggests that this
tyrosine kinase inhibitor may be a candidate for consideration as a therapeutic intervention for
ischemia-reperfusion injury.