Background & objectives: 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.
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Methods: Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (APSaline), and group III (APallopurinol) 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. zovirax. 5) was lower when compared with group II (19.2 0.6) (P
Interpretation & conclusion : 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.
Key words Acute necrotizing pancreatitis - allopurinol - bacterial translocation
Acute pancreatitis (AP) exhibits a broad clinical spectrum and its severity may range from a mild, self-limited illness to a catastrophic one with multiple potentially severe complications and risk of death1,2. In the severe form of the disease, marked pathophysiological changes in the pancreas eventually lead to multiple organ failure and high mortality rates3. Patients with infected pancreatic and peripancreatic tissue have an increased risk of developing septic complications which have emerged as the major cause of morbidity and mortality1,2,4. Contamination of necrotic tissue occurs primarily due to translocation of enteric microorganisms5. Bacterial translocation is not only specific to AP but is responsible for the development of infection and sepsis in other diseases as well6-8. Prevention of bacterial translocation may play a major role in reversing the outcome after severe pancreatitis5,9. Though various experimental models of AP have been developed, the exact mechanisms leading to this disease are not well understood.
Oxygen-derived free radicals have been suggested to play a decisive role in the pathogenesis of acute pancreatitis. Studies have demonstrated that the reactive oxygen metabolites, generated by activated xanthine oxidase enzyme, are released at an early stage of the disease10-13. Allopurinol has been shown to prevent the initial development of acute pancreatitis by inhibiting xanthine oxidase activity10-13. In addition, xanthine oxidase, an important source of endothelial cell-derived superoxide and hydrogen peroxide, has a main role in ischaemia-reperfusion injury, a mechanism contributing to intestinal barrier failure14. Hypoxia or ischaemia promotes the conversion of the NAD-reducing dehydrogenase form of the enzyme to the oxygen-reducing oxidase form. The accumulation of hypoxanthine during ischaemia allows for a burst of superoxide and hydrogen peroxide production by the enzyme when oxygen is reintroduced into the blood vessel at the time of reperfusion15.
The present study was undertaken to evaluate the effect of the allopurinol, a xanthine oxidase inhibitor, on bacterial translocation, oxidative stress and the course of acute necrotizing pancreatitis in a rat model.
Material & Methods
The experimental protocol was approved by the Institutional Animal Use and Care Committee of the Gulhane Medical Academy, Turkey and performed in accordance with the standard guidelines for the care and handling of animals.
Animals: Male Sprague-Dawley rats weighing from 280 to 350 g were obtained from Gulhane School of Medicine Research Center (Ankara, Turkey). Animals were fed standard rat chow and water ad libitum and housed in metabolic cages at controlled temperature and 12 h light/dark cycles for at least 1 wk before the experiments.
Induction of pancreatitis: Animals were anaesthetized with sevoflurane (Sevorane Liquid 250 ml, Abbott, Istanbul, Turkey) inhalation, laparotomy was performed through a midline incision. The common biliopancreatic duct was cannulated with a 28 gauge -inch, microfine catheter. One microaneurysm clip was placed on the bile duct below the liver and another around the common biliopancreatic duct at its entry into the duodenum to avoid reflux of enteric contents into the duct. Then, 1 ml/kg of 3 per cent sodium taurocholate (Sigma, USA) was slowly infused into the common biliopancreatic duct, and the infusion pressure was kept below 30 mmHg, as measured with a mercury manometer calibrated system16, and monitored with a monitoring kit (Transpac IV Safeset, Abbott, Rep. of Ireland) attached to the infusion line with a three-way stopcock. When the infusion was finished, the microclips were removed, and the abdomen was closed in two layers.