Beneficial effects of a plant histaminase in a rat model of splanchnic artery occlusion and reperfusion.
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.
Masini
Emanuela
E
Department of Preclinical and Clinical Pharmacology, University of Florence, viale G. Pieraccini, Florence, Italy. emanuela.masini@unifi.it
Cuzzocrea
Salvatore
S
Bani
Daniele
D
Mazzon
Emanuela
E
Muja
Carmelo
C
Mastroianni
Rosanna
R
Fabrizi
Francesca
F
Pietrangeli
Paola
P
Marcocci
Lucia
L
Mondovì
Bruno
B
Mannaioni
Pier Francesco
PF
Federico
Rodolfo
R
D006631:Amine Oxidase (Copper-Containing) / Q000627:therapeutic use*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D007410:Intestinal Diseases / Q000188:drug therapy; D007511:Ischemia / Q000188:drug therapy; D018532:Pisum sativum / Q000201:enzymology; D010940:Plant Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013152:Splanchnic Circulation / Q000187:drug effects*
D010940:Plant Proteins; D006631:Amine Oxidase (Copper-Containing)