Inosine reduces microcirculatory disturbance and inflammatory organ damage in experimental acute pancreatitis in rats.
BACKGROUND
Despite improvement in the management of severe necrotizing pancreatitis, mortality remains high. Today, no specific treatment exists. Inflammatory cascades and microcirculatory disturbances play a key role in the pathogenesis of acute pancreatitis. The aim of the present study was to evaluate the effects of inosine, an immunomodulatory substance, on the severity of experimental necrotizing pancreatitis.


METHODS
Severe necrotizing pancreatitis was induced in rats. Treatment groups received inosine either prophylactically or therapeutically. Pancreatic injury was evaluated by microcirculatory assessment and histology.


RESULTS
Prophylactic inosine significantly attenuated pancreatic microcirculatory disturbances and morphologic injury in necrotizing pancreatitis. However, inosine treatment did not have any beneficial effects when applied therapeutically several hours after onset of the disease.


CONCLUSIONS
Prophylactic inosine reduces microcirculatory and pancreatic injury in acute necrotizing pancreatitis. These effects should be assessed in the clinical setting of ERCP and pancreas transplantation.
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Lutz
L
Schneider
Matthias
M
Pietschmann
Werner
W
Hartwig
Sara Sevillano
SS
Marcos
Thilo
T
Hackert
Martha-Maria
MM
Gebhard
Waldemar
W
Uhl
Markus W
MW
Büchler
Jens
J
Werner
D000704:Analysis of Variance; D000818:Animals; D007249:Inflammation / Q000517:prevention & control; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D007288:Inosine