Submitted on November 16, 2007
Accepted on February 21, 2008
The tripeptide analogue feG, ameliorates severity of acute pancreatitis in a caerulein mouse model
Yusnita Rifai1, Alison SF Elder2, Colin J Carati3, Damian James Hussey4, Xin Li4, Charmaine Michelle Woods4, Ann Carolyn Schloithe4, Anthony C Thomas5, Ronald D Mathison6, Joseph S. Davison7, James Toouli1, and Gino Tony P Saccone4*
1 Surgery, Flinders University, Adelaide, South Australia, Australia
2 Surgery, Flinders University, Adelaide, Australia
3 School of Medicine, Flinders University, Adelaide, South Australia, Australia
4 Surgery, Flinders University, Adelaide, South Australia, Australia; Adelaide, South Australia, Australia
5 Anatomical Pathology, Flinders University, Adelaide, South Australia, Australia
6 Physiology and Biophysics, University of Calgary, Calgary, Canada
7 Dept. of Physiology & Biophysics, University of Calgary, Faculty of Med., Calgary, Canada
* To whom correspondence should be addressed. E-mail: gino.saccone{at}flinders.edu.au.
Acute pancreatitis (AP) is associated with significant morbidity and mortality, however there is no specific treatment for this disease. A novel salivary tripeptide analogue feG, reduces inflammation in several different animal models of inflammation. The aims of this study were to determine if feG reduced the severity of AP and modifies the expression of pancreatic intercellular adhesion molecule-1 (ICAM-1) mRNA during AP in a mouse model. AP was induced in mice by hourly (x12) intraperitoneal injections of caerulein. A single dose feG (100 µg/kg) was co-administered with caerulein either at time 0 h (prophylactic) or 3 h post-AP induction (therapeutic). Plasma amylase and pancreatic myeloperoxidase (MPO) activities and pancreatic ICAM-1 mRNA expression (by RT-PCR) were measured. Pancreatic sections were histologically assessed for abnormal acinar cells and interstitial space. AP induction produced a 7-fold increase in plasma amylase, a 10-fold increase in pancreatic MPO activity, a 3-fold increase in interstitial space and 90% of the acinar cells were abnormal. Prophylactic treatment with feG reduced the AP-induced plasma amylase activity by 45%, pancreatic MPO by 80%, the proportion of abnormal acinar cells by 30% and interstitial space by 40%. Therapeutic treatment with feG significantly reduced the AP-induced abnormal acinar cells by 10% and the interstitial space by 20%. Pancreatic ICAM-1 mRNA expression was upregulated in AP and was reduced by 50% with prophylactic and therapeutic treatment with feG. We conclude that feG ameliorates experimental AP acting at least in part by modulating ICAM-1 expression in the pancreas.
