title: New insights into the methodology of L-arginine-induced acute pancreatitis.
abstract: Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5-30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h., In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L-arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5-8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice.
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Balázs
authors: B
authors: Kui
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Zsolt
authors: Z
authors: Balla
authors: Department of Pathology, University of Szeged, Szeged, Hungary.
authors: Béla
authors: B
authors: Vasas
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Eszter T
authors: ET
authors: Végh
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Petra
authors: P
authors: Pallagi
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Eszter S
authors: ES
authors: Kormányos
authors: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
authors: Viktória
authors: V
authors: Venglovecz
authors: Department of Pathology, University of Szeged, Szeged, Hungary.
authors: Béla
authors: B
authors: Iványi
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Tamás
authors: T
authors: Takács
authors: First Department of Medicine, University of Szeged, Szeged, Hungary; Hungarian Academy of Sciences-University of Szeged, Translational Gastroenterology Research Group, Szeged, Hungary.
authors: Péter
authors: P
authors: Hegyi
authors: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors: Zoltán
authors: Z
authors: Rakonczay
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism
chemical_list: D001120:Arginine; D009195:Peroxidase; D000681:Amylases