Journal Article

New Insights into the Methodology of L-Arginine-Induced Acute Pancreatitis

Balla, Zsolt, Takács, Tamás, Vasas, Béla, Kormányos, Eszter S., Végh, Eszter T., Pallagi, Petra, Iványi, Béla, Kui, Balázs, Venglovecz, Viktória, Hegyi, Péter, Rakonczay, Zoltán

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino acids / Amylases - blood / Analysis / Animal models / Animals / Arginine / Disease / Disease Models, Animal / Drug dosages / Euthanasia / Female / Gangrene / Gastroenterology / Gender / House mouse / Laboratory animals / Male / Medical research / Medicine / Methods / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Necrosis / Pancreas / Pancreas - drug effects / Pancreas - metabolism / Pancreatitis / Pancreatitis, Acute Necrotizing - chemically induced / Pancreatitis, Acute Necrotizing - metabolism / Peroxidase - metabolism / Rodents