Polyamine Catabolism in Relation to Trypsin Activation and Apoptosis in Experimental Acute Pancreatitis

Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research

“…Thereafter, the model was employed frequently to explore the pathogenesis of AP with a commonly adopted regimen of 200 µl of 5% Na‐TDC in the rat. Common findings included the perturbation of energy metabolism in the intestinal wall, 44 impaired intestinal permeability, 45 bacterial translocation, 46,47 formation of platelet‐activating factor, 48 pulmonary endothelial barrier dysfunction, 49 microvascular endothelial barrier dysfunction, 50 activation of mast cells, 51–53 induction of nitric oxide synthase, 54 over‐induced polyamine catabolism, 55–57 increased high‐mobility group box, 58 increased catalytic activity of phospholipase A, 59 upgraded cytokine levels 60,61 and increased myeloperoxidase (MPO) activity 61 …”

Elevated Deoxycholic Acid and Idiopathic Recurrent Acute Pancreatitis: A Case Report with 48 Months of Follow-up

“…This is despite the fact that scientists have, for many decades, infused three forms of DCA into experimental animals to induce reproducible pancreatic injury. The three forms include the bile salt sodium deoxycholate, [7][8][9] the taurine conjugated bile salt (taurodeoxycholate), 10 and the glycine conjugated bile acid (glycodeoxycholic acid). [11][12][13] To understand the potential role of the microbiome in pancreatitis requires a brief review of bile acids and their metabolism.…”

Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research

“…Importantly, TLCS which has been extensively characterized in vitro, is generally preferred over NaTC for inducing PDI-AP, especially after the identification of the G protein-coupled bile acid receptor1 (Gpbar1) present on the apical pole of PACs (Perides et al, 2010). Mice lacking this receptor (Gpbar1 −/− ) were completely protected against AP induced by TLCS in vivo as well as treatment with 500 µM TLCS of PACs isolated from these mice did not result in pathophysiological Ca 2+ responses, intrapancreatic trypsinogen activation, and cell death that are normally seen in wild type Sun et al, 2006Sun et al, , 2007 NaGDC 8.5, 17, or 34 mM 100 µl Rats NaGDC at concentrations of 8.5-34 mM caused progressive severe but non-lethal acute pancreatitis in rats; 17 and 34 mM NaGDC infusion produced oedematous and necrotizing pancreatitis respectively; when 200 ng EK was infused with 34 mM NaGDC, necrotising pancreatitis with systemic disturbance, and rapid lethality was produced Terry et al, 1987;Rattner et al, 1990;Rosen and Tuchler, 1992 5 or 10 mM 100-150 µl Rats Low concentration of NaGDC with i.v., caerulein 5 µg/kg/h injection for 6 h caused features of moderate onset, homogeneous moderate pancreatic injury that lasts over at least 24 h Schmidt et al, 1992a,b NaTDC 2, 5, or 6% 200 µl Rats 2% NaTDC infusion caused pancreatic oedema, leukocytosis, and gradually increase of acinar cell necrosis over time until 24 h; with higher concentration at 5 or 6%, pancreatic necrosis progressed more rapidly Jin et al, 2008Jin et al, , 2011Lopez-Font et al, 2010 NaTC 3, 4.5, or 5% 1 ml/kg Rats Significantly increased serum amylase, lipase, and pro-inflammatory cytokine levels; pancreatic oedema, vacuolisation, inflammation, hemorrhage, acinar cell and fat necrosis; lung, liver, gastric, kidney, and brain injuries; at concentrations of 3.0, 4.5, or 5.0% induced 72 h mortality rates of 24, 71, and 100%, respectively. Paszt et al, 2004;Yang et al, 2004;Leveau et al, 2005;Dang et al, 2007;Zhang et al, 2007;Chen et al, 2008;de Campos et al, 2008;Qian et al, 2010;Xia et al, 2010;Jung et al, 2011 2, 4, or 5% 2 ml/kg Mice 2% NaTC caused oedema, leukocyte infiltration, necrosis, hemorrhage, and fat necrosis of the pancreas without lung injury and lethality; higher dose of NaTC increased pulmonary BAL fluid albumin and myeloperoxidase activity, and mortality: 10 and 60% mortality rates at 24 h for 4 an...…”