The role of allopurinol in experimental acute necrotizing pancreatitis.
OBJECTIVE
Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model.


METHODS
Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (AP+Saline), and group III (AP+allopurinol) by retrograde infusion of taurocholate into the common biliopancreatic duct. Group I rats (Sham) received normal saline infusion into the common biliopancreatic duct for mimicking pressure effect. Group III rats were treated with allopurinol intraperitoneally for 48 h after induction of pancreatitis. Blood samples were drawn from all animals for biochemical analyses and pancreatic tissues were examined for bacterial translocation.


RESULTS
Acute pancreatitis was developed in all groups, but not in group I (Sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Pathologic score of the pancreatitis in the allopurinol group (14.0 +/- 0.5) was lower when compared with group II (19.2 +/- 0.6) (P<0.001). Bacterial translocation to pancreas in group treated with allopurinol was significantly lower when compared with control group (p<0.02). Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were higher and malondialdehyde (MDA) levels were lower in allopurinol group when compared with those in control groups.


CONCLUSIONS
Our findings suggested that addition of allopurinol to the treatment protocol in the acute pancreatitis might improve the pathologic score, bacterial translocation and oxidative stress parameters. However, more studies need to be done to confirm these findings.
Isik
A Turan
AT
Department of Internal Medicine, Gulhane School of Medicine, Baskent University, Ankara, Turkey. ahmetturanisik@yahoo.com
Mas
M Refik
MR
Yamanel
Levent
L
Aydin
Sezai
S
Comert
Bilgin
B
Akay
Cemal
C
Erdem
Gokhan
G
Mas
Nuket
N
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D018988:Bacterial Translocation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000493:Allopurinol; D014969:Xanthine Oxidase