Development of a new mouse model of acute pancreatitis induced by administration of L-arginine.
The pathogenesis of acute pancreatitis is not fully understood. Experimental animal models that mimic human disease are essential to better understand the pathophysiology of the disease and to evaluate potential therapeutic agents. Given that the mouse genome is known completely and that a large number of strains with various genetic deletions are available, it is advantageous to have multiple reliable mouse models of acute pancreatitis. Presently, there is only one predominant model of acute pancreatitis in mice, in which hyperstimulatory doses of cholecystokinin or its analog caerulein are administered. Therefore, the aim of this study was to develop another mouse model of acute pancreatitis. In this study, C57BL/6 mice were injected intraperitoneally with L-arginine in two doses of 4 g/kg each, 1 h apart. Serum amylase, myeloperoxidase, and histopathology were examined at varying time points after injection to assess injury to the pancreas and lung. We found that injection of L-arginine was followed by significant increases in plasma amylase and pancreatic myeloperoxidase accompanied by marked histopathological changes. The injury to the pancreas was slow to develop and peaked at 72 h. Subsequent to peak injury, the damaged areas contained collagen fibers as assessed by increased Sirius red staining. In contrast, D-arginine or other amino acids did not cause injury to the pancreas. In addition, acute inflammation in the pancreas was associated with lung injury. Our results indicate that administration of L-arginine to mice results in severe acute pancreatitis. This model should help in elucidating the pathophysiology of pancreatitis.
Dawra
Rajinder
R
Department of Surgery, University of Minnesota, MMC 195, 420 Delaware St. SE, Minneapolis, MN 55416, USA.
Sharif
Rifat
R
Phillips
Phoebe
P
Dudeja
Vikas
V
Dhaulakhandi
Dhara
D
Saluja
Ashok K
AK
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005355:Fibrosis; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
D003094:Collagen; D001120:Arginine; D009195:Peroxidase; D000681:Amylases; D014357:Trypsin