Leflunomide: is a new oral agent in treatment of acute pancreatitis?
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.
Kutluana
Ufuk
U
Department of Gastroenterology, Faculty of Medicine, Pamukkale University, Denizli, Turkey. ukutluana@pau.edu.tr
Oruc
Nevin
N
Nart
Deniz
D
Kaptanoglu
Bunyamin
B
Yonetci
Nadir
N
Ozutemiz
Omer
O
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
D000893:Anti-Inflammatory Agents; D007555:Isoxazoles; D009569:Nitric Oxide; D008315:Malondialdehyde; D013656:Taurocholic Acid; D009195:Peroxidase; D000681:Amylases; D000077339:Leflunomide