Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis.
BACKGROUND
Xanthine oxidoreductase has been proposed to play a role in the development of local and systemic effects of acute pancreatitis. Under physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH) but can be converted by proteolytic cleavage to its superoxide-generating form xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also associated to the polysaccharide chains of proteoglycans on the external endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme seems to be arising from its mobilization from the gastrointestinal endothelial cell surface. Taking into account the ability of alpha-amylase to hydrolyze the internal alpha-1,4 linkages of polysaccharides, we wanted to elucidate the involvement of alpha-amylase in XDH/XOD mobilization from the gastrointestinal endothelial cell surface and the relevance of the ascitic fluid (AF) as the source of alpha-amylase in experimental acute pancreatitis.


METHODS
Acute pancreatitis was induced in male Wistar rats by intraductal administration of 5% sodium taurocholate. In another experimental group 3000 U/Kg alpha-amylase was i.v. administered. The concentrations of XDH, XOD and alpha-amylase in plasma and AF and myeloperoxidase (MPO) in lung have been evaluated. In additional experiments, the effect of peritoneal lavage and the absorption of alpha-amylase present in the AF by an isolated intestine have been determined.


RESULTS
Similar increase in XDH+XOD activity in plasma was observed after induction of acute pancreatitis and after i.v. administration of alpha-amylase. Nevertheless, the conversion from XDH to XOD was only observed in the pancreatitis group. Lung inflammation measured as MPO activity was observed only in the pancreatitis group. In addition peritoneal lavage prevented the increase in alpha-amylase and XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that alpha-amylase is absorbed from the AF by the intestine.


CONCLUSIONS
During the early stages of acute pancreatitis, alpha-amylase absorbed from AF through the gastrointestinal tract could interfere with the binding of XDH/XOD attached to glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its oxidase form promoting an increase in circulating XOD that has been reported to be one of the mechanisms involved in the triggering of the systemic inflammatory process.
Granell
Susana
S
Dept, of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. sgbbam@iibb.csic.es
Bulbena
Oriol
O
Genesca
Meritxell
M
Sabater
Luis
L
Sastre
Juan
J
Gelpi
Emilio
E
Closa
Daniel
D
D000208:Acute Disease; D000681:Amylases / Q000493:pharmacokinetics*; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D001667:Binding, Competitive; D004727:Endothelium / Q000201:enzymology; D007408:Intestinal Absorption; D008168:Lung / Q000201:enzymology; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D013656:Taurocholic Acid; D009195:Peroxidase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D000681:Amylases