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Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

We have previously shown that chenodeoxycholic acid (CDCA) strongly inhibits pancreatic ductal HCO3 (-) secretion through the destruction of mitochondrial function, which may have significance in the pathomechanism of acute pancreatitis (AP). Ursodeoxycholic acid (UDCA) is known to protect the mitochondria against hydrophobic bile acids and has an ameliorating effect on cell death. Therefore, our aim was to investigate the effect of UDCA pretreatment on CDCA-induced pancreatic ductal injury. Guinea pig intrainterlobular pancreatic ducts were isolated by collagenase digestion. Ducts were treated with UDCA for 5 and 24 h, and the effect of CDCA on intracellular Ca(2+) concentration ([Ca(2+)]i), intracellular pH (pHi), morphological and functional changes of mitochondria, and the rate of apoptosis were investigated. AP was induced in rat by retrograde intraductal injection of CDCA (0.5%), and the disease severity of pancreatitis was assessed by measuring standard laboratory and histological parameters. Twenty-four-hour pretreatment of pancreatic ducts with 0.5 mM UDCA significantly reduced the rate of ATP depletion, mitochondrial injury, and cell death induced by 1 mM CDCA and completely prevented the inhibitory effect of CDCA on acid-base transporters. UDCA pretreatment had no effect on CDCA-induced Ca(2+) signaling. Oral administration of UDCA (250 mg/kg) markedly reduced the severity of CDCA-induced AP. Our results clearly demonstrate that UDCA 1) suppresses the CDCA-induced pancreatic ductal injury by reducing apoptosis and mitochondrial damage and 2) reduces the severity of CDCA-induced AP. The protective effect of UDCA against hydrophobic bile acids may represent a novel therapeutic target in the treatment of biliary AP., (Copyright © 2016 the American Physiological Society.)

Pediatric pancreatitis is a rare disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has been increased. The management of pediatric pancreatitis requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. In 8 clinical topics (diagnosis; etiology; prognosis; imaging; therapy; biliary tract management; complications; chronic pancreatitis) 50 relevant questions were defined. Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinical statements were accepted with total (more than 95%) agreement. The present Hungarian Pancreatic Study Group guideline is the first evidence based pediatric pancreatitis guideline in Hungary. The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care in pediatric pancreatitis and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

Autoimmune pancreatitis is a rare disease which can even mimic pancreatic tumor, however, unlike the latter, it requires not surgical but conservative management. Correct diagnosis and differential diagnosis of autoimmune pancreatitis and treatment of these patients requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 29 relevant clinical questions in 4 topics were defined (Basics; Diagnosis; Differential diagnostics; Therapy). Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinial questions were accepted with almost total (more than 95%) agreement. The present guideline is the first evidence based autoimmune pancreatitis guideline in Hungary. The guideline may provide very important and helpful data for tuition of autoimmune pancreatitis, for everyday practice and for establishing proper finance. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

Acute pancreatitis is one of the most common diseases of the gastrointestinal tract associated with significant morbidity and mortality that requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare evidence based guideline for the medical and surgical management of acute pancreatitis based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and, if it was necessary, complemented and/or modified the international guidelines. All together 42 relevant clinical questions were defined in 11 topics (Diagnosis and etiology, Prognosis, Imaging, Fluid therapy, Intensive care management, Prevention of infectious complications, Nutrition, Biliary interventions, Post-endoscopic retrograde cholangio-pancreatography pancreatitis, Indication, timing and strategy for intervention in necrotizing pancreatitis, Timing of cholecystectomy [or endoscopic sphincterotomy]). Evidence was classified according to the UpToDate® grading system. The draft of the guideline was presented and discussed at the consensus meeting on September 12, 2014. 25 clinical questions with almost total (more than 95%) and 17 clinical questions with strong (more than 70%) agreement were accepted. The present guideline is the first evidence based acute pancreatitis guideline in Hungary. The guideline may provide important help for tuition, everyday practice and for establishment of proper finance of acute pancreatitis. Therefore, the authors believe that these guidelines will widely become as basic reference in Hungary.

Pancreatic endocrine and/or exocrine functional disorders can be commonly detected in patients with inflammatory bowel diseases. Autoimmune pancreatitis is a rare disease and its co-existence with inflammatory bowel disease has been rarely reported. The diagnosis of autoimmune pancreatitis is difficult due to variable nonspecific symptoms, and the high rate of asymptomatic cases. The conventional imaging scans (ultrasonography, computed tomography, retrograde cholangiography) are usually not sensitive enough and they are frequently not able to differentiate between inflammatory and malignant tumorous diseases of the pancreas. The authors present the case history of a patient who developed both ulcerative colitis and autoimmune pancreatitis. The morphological changes of the pancreas detected by ultrasonography suggested the presence of pancreatic cancer, and this diagnosis was supported by the elevated level of serum CA19-9. Computed tomography failed to identify abnormalities in the pancreas and, finally, endoscopic ultrasound combined with fine needle aspiration cytology confirmed the diagnosis of autoimmune pancreatitis.

Conventional radiologic imaging (abdominal ultrasound, computer tomography) used in the differential diagnosis of post-hepatic jaundice can frequently provide inaccurate diagnosis. Inflammatory lesions may mimic neoplastic processes and malignancy may be accompanied by perifocal inflammation resulting in histological misdiagnosis. Furthermore, chronic and autoimmune pancreatitis are associated with an increased risk for pancreatic cancer. Radial endosonography has become a markedly important method in the imaging of the pancreas. It has a crucial role in the diagnosis and staging of pancreatic cancer. The authors present three cases where the diagnosis of pancreatic cancer determined by conventional imaging techniques (abdominal ultrasound, computer tomography, endoscopic retrograde cholangiopancreatography) was excluded or confirmed by the radial endosonography. The authors conclude that radial endosonography is an essential complementary method among imaging techniques of the pancreas and in tumor staging. Application of that may prevent unnecessary surgeries, which is obviously useful for patients and cost effective for health care providers.

Background: To date, most cases of autoimmune pancreatitis (AIP) have been reported from Japan. The aim of the present study was to assess the clinical features and management of AIP cases in Hungary., Methods: The demographics, clinical presentation, laboratory and imaging findings, extrapancreatic involvement, treatment response and recurrence were evaluated in the first 17 patients diagnosed with AIP in Hungary., Results: The mean age at presentation was 42.7 years (range: 16-74); 47% of the patients were women. New-onset mild abdominal pain (76%), weight loss (41%) and jaundice (41%) were the most common symptoms, with inflammatory bowel disease being the most frequent (36%) extrapancreatic manifestation. Diffuse pancreatic swelling was seen in 7 patients (41%) and a focal pancreatic mass in 8 (47%). Endoscopic retrograde cholangiopancreatography revealed pancreatic duct strictures in all study patients. The serum IgG4 level at presentation was elevated in 62% of the 8 patients in whom it was measured. All the percutaneous core biopsies (5 patients) and surgical specimens (2 patients), and 2 of the 4 biopsies of the papilla of Vater revealed the typical characteristic findings of AIP: a diffuse lymphoplasmacytic infiltration, marked interstitial fibrosis and obliterative phlebitis. Immunostaining indicated IgG4-positive plasma cells in 62% of the 8 patients in whom it was performed. Granulocytic epithelial lesions (GEL) were present in 3 patients. The patients without GELs were older (mean age 59 years), while those with GEL were younger (mean age 34 years), and 2 of 3 were female and had ulcerative colitis. A complete response to steroid treatment was achieved in all 15 patients. Because of the suspicion of a pancreatic tumor, 2 patients with focal AIP underwent partial pancreatectomy. One patient relapsed, but responded to azathioprine., Conclusions: This first Hungarian series has confirmed several previously reported findings on AIP. AIP with GEL was relatively frequent among our patients: these patients tended to be younger than in earlier studies and displayed a female preponderance with a high coincidence of ulcerative colitis. Performance of a percutaneous biopsy is strongly recommended. The response to immunosuppressive therapy was excellent. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

The proteosome inhibitor bortezomib is used in the treatment of patients with multiple myeloma. Proteosomes are responsible for the degradation of I-kappaB, the inhibitory protein of transcription factor nuclear factor kappa B (Nf-kappaB). The heat shock protein (HSP) inducing effect of bortezomib is also documented. The aim of our work was to test the anti-inflammatory effect of bortezomib in cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis. Male Wistar rats were divided into three groups (n=8 in each). Group P received an i.p. injection of physiological saline (p.s.) 60 min. before the induction of acute pancreatitis by three hourly s.c. injections of 100 microg/kg CCK-8. Group BP received 1 mg/kg bortezomib dissolved in p.s. 1 h previous to pancreatitis induction. Group C was treated with the vehicle (p.s.). Animals were exsanguinated 4 h after the last injection of CCK-8. Bortezomib pre-treatment significantly reduced the pancreatic weight/body weight ratio, and improved the histology by decreasing the extent of vacuolization and infiltration. Bortezomib pre-treatment inhibited I-kappaBbeta degradation, and induced the synthesis of HSP72. The results confirmed the anti-inflammatory effect of bortezomib in acute experimental pancreatitis. This effect of the drug is presumably mediated by the inhibition of Nf-kappaB activation and induction of HSP synthesis.

Objectives: To investigate the consequences of treatment with an exogenous glucocorticoid agonist (methylprednisolone) and antagonist (RU-38486) on the local and systemic responses in L-arginine-induced acute pancreatitis in rats., Methods: The methylprednisolone and RU-38486 were administered just before pancreatitis induction. Plasma amylase activity, interleukin 6 activity, pancreatic weight/body weight ratio, plasma macrophage migration inhibitory factor (MIF) concentration, and pancreatic nuclear transcription factor (NF) kappaB activity were determined. The extents of pancreas, liver, and lung injuries were assessed by histology., Results: Acute pancreatitis resulted in NF-kappaB activation and proinflammatory cytokine release in rats. In the glucocorticoid agonist group, plasma amylase and interleukin 6 levels were significantly decreased as compared with those of RU-38486 and nontreated groups. Antagonist treatment led to significantly higher MIF production at 8 and 12 hours after L-arginine injection as compared with the agonist-treated and nontreated groups. Glucocorticoid agonist treatment significantly decreased the level of NF-kappaB 24 hours after pancreatitis induction. Histological investigations showed protective effect of agonist treatment on acute pancreatitis-induced tissue damage in the pancreas and lung., Conclusions: These results corroborated the importance of MIF in acute pancreatitis. The glucocorticoid-dependent mechanisms seem to play a crucial role in the control of the inflammatory response and tissue damage in L-arginine-induced experimental acute pancreatitis.

Objective: Our experiments were designed to investigate the effects of zerumbone pretreatment on cholecystokinin octapeptide (CCK-8)-induced acute pancreatitis in rats., Methods: Male Wistar rats weighing 240 to 280 g were divided into a control group, a group treated with CCK-8, a group receiving 20 mg/kg zerumbone before CCK-8 administration, and a group treated with zerumbone only., Results: The serum amylase and lipase activities and the pancreatic weight-body weight ratio were significantly reduced by zerumbone pretreatment, but the drug failed to influence the histological parameters of pancreatitis. The anti-inflammatory effects of the drug were manifested in decreases in the cytosolic interleukin 6 and tumor necrosis factor alpha concentrations and an elevation in the I-kappaB concentration, whereas the antioxidant ability of zerumbone was demonstrated by reductions in inducible nitric oxide synthase, Mn- and Cu/Zn-superoxide dismutase activities in the zerumbone-treated rats., Conclusion: Zerumbone ameliorated the changes of several parameters of acute pancreatitis probably by interfering with I-kappaB degradation, but in the applied dose, it failed to influence the histology of the disease.

Aim: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis., Methods: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 microg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK., Results: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kappaB (NF-kappaB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress., Conclusion: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.

Resveratrol is a phytoalexin with strong antioxidant and anti-inflammatory effects reaching high concentrations in red wine. The aim of our study was to test the effects of resveratrol pretreatment on cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis in rats. Animals were divided into a control group, a group treated with CCK-8 and a group receiving 10 mg/kg resveratrol prior to CCK-8 administration. Resveratrol ameliorated the CCK-8-induced changes in the laboratory parameters, and reduced the histological damage in the pancreas. The drug failed to improve the pancreatic antioxidant state, but increased the amount of hepatic reduced glutathione and prevented the reduction of hepatic catalase activity. Resveratrol-induced inhibition of nuclear factor kappa B (NF-kappaB) activation or reduction of the pancreatic tumor necrosis factor-alpha (TNF-alpha) concentration could not be demonstrated. In conclusion, the beneficial effects of resveratrol on acute pancreatitis seem to be mediated by the antioxidant effect of resveratrol or by an NF-kappaB-independent anti-inflammatory mechanism.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements, and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations, and histology. In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity, and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Background: The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. To investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486), and to characterize the local and systemic responses in experimental AP., Methods: The glucocorticoid agonists and antagonist were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations and histology., Results: In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups., Conclusions: These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Introduction: Nitric oxide (NO) has been implicated in the regulation of the pancreatic circulation, the promotion of the capillary integrity, and the inhibition of leukocyte adhesion., Aims: To investigate the rates of changes in the pancreatic constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities and the role of NO in the vascular permeability changes during the development of L-arginine (Arg)-induced acute pancreatitis., Methodology: Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of Arg i.p. twice at an interval of 1 hour, as a 20% solution in 0.15 NaCl (group I). The control rats received the same quantity of glycine (group II). In group III, 30 mg/kg N -nitro-L-arginine methyl ester (L-NAME) was injected i.p. 19 hours after the first Arg injection. The rats were killed at 6, 12, 24, or 48 hours following Arg administration, and the plasma amylase concentration and the pancreatic weight/body weight (pw/bw) ratios were evaluated. NOS activity was determined via the conversion of L- C-Arg monohydrochloride to C-citrulline. The vascular permeability was examined by means of the extravasation of Evans blue dye (20 mg/kg bw) into the pancreatic tissue., Results: The serum amylase level was already increased at 6 hours in group I animals, peaked at 12 hours after the Arg injection (11.800 +/- 590 versus 6.618 +/- 252 U/L in group II), and returned to the control level at 48 hours. The pw/bw ratio peaked at 24 hours in group I (6.63 +/- 0.52 versus 4.02 +/- 0.22 mg/g in group II) and returned to the control level at 48 hours. The cNOS activity was depleted at 6 hours in group I (0.02 +/- 0.003 versus 0.23 +/- 0.02 pmol/min/mg protein in group II); it then gradually increased to a level significantly higher than that in group II and decreased thereafter (0.45 +/- 0.03 and 0.13 +/- 0.01 pmol/min/mg protein at 24 and 48 hours). The iNOS activity was significantly increased at 24 and 48 hours versus that in group II (0.15 +/- 0.05 and 0.07 +/- 0.01 versus 0.04 +/- 0.01 pmol/min/mg protein). The pancreatic concentration of Evans blue dye was significantly higher in group I than in group II (138.59 +/- 11.04 versus 43.57 +/- 2.67 (g/dry weight). Treatment with L-NAME significantly reduced the amylase activity, pw/bw, Evans blue concentration, and cNOS activity of the pancreas but did not exert any beneficial effect on the histologic score at 24 hours after the onset of pancreatitis, as compared with those values in group I (6.528 +/- 673 U/L, 4.56 +/- 0.65 mg/g, 86.84 +/- 3.9 (g/dry weight, 0.14 +/- 0.04 pmol/min/mg protein)., Conclusion: Endogenous NO is involved in the formation of pancreatic edema in Arg-induced acute pancreatitis by increasing the vascular permeability and protein extravasation. L-NAME treatment decreased the cNOS activity and edema formation but did not prevent the histologic damage in Arg-induced acute pancreatitis.

Background: The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol., Methods: Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney., Results: The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney., Conclusion: Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800+/-3813 vs 6382+/-184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00+/-1.75 vs 0.28+/-0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631+/-2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55+/-0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.