Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and
inflammation which contribute to the pathophysiology of
shock. We investigated the effects of pea seedling (Latyrus cicera)
histaminase, known to afford protection against the deleterious effects of cardiac
ischemia/reperfusion, given to rats subjected to SAO/reperfusion-induced splanchnic injury.
Histaminase (80 IU kg, 15 min before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/reperfusion.
Histaminase also reduced histopathological changes, leukocyte infiltration (
myeloperoxidase), and expression of endothelial cell adhesion molecules in the ileum.
Histaminase counteracted
free radical-mediated tissue injury, as judged by a significant decrease in the plasma and tissue levels of peroxidation and nitration products (oxidized
rhodamine,
malondialdehyde,
nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-adenosine diphosphate-ribosylated DNA) and consumption of tissue
antioxidant enzymes (
superoxide dismutase). As a result,
histaminase led to a reduction of ileal cell apoptosis (
caspase 3, terminal
deoxynucleotidyltransferase-mediated
UTP end labeling-positive cells). These results show that
histaminase exerts a clear-cut protective effect in SAO/reperfusion-induced splanchnic injury, likely caused by oxidative catabolism of proinflammatory
histamine and
antioxidant effects resulting in hindrance of
free radical-mediated tissue injury, endothelial dysfunction, and leukocyte recruitment. Thus,
histaminase could be used therapeutically in intestinal
ischemia.