title: Leflunomide: is a new oral agent in treatment of acute pancreatitis?
abstract: OBJECTIVE
  Nuclear factor-kappaB (NF-kappaB) is a potent mediator in several steps of acute pancreatitis. Leflunomide is a novel immunomodulating drug that is also a potent inhibitor of NF-kappaB activation. The aim of this study was to investigate the effects of leflunomide pretreatment in severe necrotizing pancreatitis in rats.
  
  
  METHODS
  Fifty rats were randomly divided into 5 groups. Severe necrotizing pancreatitis was induced by retrograde injection of 3% sodium taurocholate into the common biliopancreatic duct. Leflunomide (10 mg/kg) was given intragastrically for 2 doses before the experiment. Serum amylase activity, pancreatic histopathologic condition, malondialdehyde level, myeloperoxidase enzyme activity, nitric oxide level, and pulmonary changes were assessed.
  
  
  RESULTS
  Leflunomide pretreatment significantly ameliorated pancreatic hemorrhage, edema, and neutrophil infiltration and decreased histopathological score compared with the untreated severe necrotizing pancreatitis group (pathological score [mean +/- SEM]: 6.70 +/- 1.19 vs 12.36 +/- 1.08 in the leflunomide treated and untreated groups, respectively, P < 0.01). Pulmonary changes was decreased in the leflunomide treated group (3.90 +/- 0.45 vs 4.75 +/- 0.25, respectively). Change in pulmonary alveolar distention was significant. Although serum amylase levels also decreased, the difference was not significant (5922 +/- 3290 vs 15547 +/- 5090 U/mL).
  
  
  CONCLUSIONS
  Leflunomide is a beneficial agent in the severe form of acute pancreatitis in rats and should be considered as a potential agent for treatment of acute pancreatitis.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Pamukkale University, Denizli, Turkey. ukutluana@pau.edu.tr
authors.forename: Ufuk
authors.initials: U
authors.lastname: Kutluana
authors.forename: Nevin
authors.initials: N
authors.lastname: Oruc
authors.forename: Deniz
authors.initials: D
authors.lastname: Nart
authors.forename: Bunyamin
authors.initials: B
authors.lastname: Kaptanoglu
authors.forename: Nadir
authors.initials: N
authors.lastname: Yonetci
authors.forename: Omer
authors.initials: O
authors.lastname: Ozutemiz
mesh_terms: D000284:Administration, Oral; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007555:Isoxazoles / Q000008:administration & dosage*; D000077339:Leflunomide; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013656:Taurocholic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D007555:Isoxazoles; D009569:Nitric Oxide; D008315:Malondialdehyde; D013656:Taurocholic Acid; D009195:Peroxidase; D000681:Amylases; D000077339:Leflunomide