Poly(ADP-ribose) polymerase (PARP), a nuclear
enzyme activated by strand breaks in
DNA, plays an important role in the tissue injury associated with
ischemia-reperfusion and
inflammation. Splanchnic artery occlusion and reperfusion causes an enhanced formation of
reactive oxygen species which contribute to the pathophysiology of
shock. The aim of the present study was to investigate the effects of
5-aminoisoquinolinone (5-AIQ), a potent water-soluble inhibitor of
poly(ADP-ribose) polymerase (PARP), in the pathogenesis of splanchnic artery occlusion
shock. Splanchnic artery occlusion
shock was induced in rats by clamping both the superior mesenteric artery and the celiac artery for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, all animals were sacrificed for histological examination and biochemical studies. Treatment of rats with
5-AIQ (3 mg/kg i.v.), attenuated the fall of mean arterial blood pressure caused by splanchnic artery occlusion
shock.
5-AIQ also attenuated the ileum injury as well as the increase in the tissue levels of
myeloperoxidase and
malondialdehyde caused by splanchnic artery occlusion
shock in the ileum. The immunohistochemical examination also demonstrated a marked increase in the immunoreactivity to PAR,
nitrotyrosine, and
intercellular adhesion molecule (ICAM-1) in the necrotic ileum from splanchnic artery occlusion-shocked rats.
5-AIQ treatment significantly reduced the increase of positive staining for PAR,
nitrotyrosine and ICAM-I. In conclusion, these results show that
5-AIQ, a new water-soluble potent inhibitor of
poly(ADP-ribose) polymerase, exerts multiple protective effects in splanchnic artery occlusion/reperfusion
shock.