Induction of Chronic Pancreatic Disease by Trinitrobenzene Sulfonic Acid Infusion into Rat Pancreatic Ducts

Abstract

Despite being a common disease in humans,little is known about the etiopathogenesis of and effective therapeutic approaches to chronic pancreatitis, due mainly to the fact that few simple animal models suitable to study inflammatory and fibrogenetic processes have been described in the pancreas. 'l'rinitrobenzene sulfonic acid (I'NBS) induces chronic colitis and cholangitis in the rat. We hypothesized that TNBS instillation into the pancreatic ducts could also result in the development of a chronic pancreatic disease. The biliopancreatic duct of rats was cannulated and tied close to the liver. TNBS 10.4 ml of 2% 'I'NBS in phosphate-buffered saline (PBS)-10% ethanol, pH 81 was infused into the pancreas under a continuous controlled-pressure system. Control rats underwent the same procedure using vehicle only. Pathology assessment of TNBS-treated rats examined at 48 h was consistent with severe acute necrotizing pancreatitis, having a mortality rate of 3 1% and serum amylase activity of 37.4 * 8.8 U/ml at 24 h and 13.3 i 1.7 Uiml at 48 h ( p < 0.01 for both time points compared to PBSiethanoltreated rats). Groups of 10 rats each were killed at 3, 4, and 6 weeks after the surgical procedure. Morphological examination revealed changes mimicking features of chronic pancreatitis in humans in 80%) (32 of 40) of TNBStreated rats, consisting in various degrees of periductal and lobular fibrosis, duct stenosis, patchy acute and chronic inflammatory cell infiltrates, and signs of gland atrophy. Animals developing chronic disease had a weight gain rate significantly lower than that of control rats. Serum amylase, fasting glucose, and a glucose tolerance test were not different in diseased o r control rats. In conclusion, we were able to induce chronic fibrogenetic inflammatory disease in the pancreas after a single pulse instillation of TNBS into the pancreatic ducts. This might be a useful animal model to study the pathophysiology of inflammatory, fibrogenetic, and reparative processes in pancreatic tissue.

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis

“…Care and handling of these animals were approved by the Institutional Animal Care and Use Committee at the University of Texas Medical Branch and were in accordance with the guidelines of the International Association for the Study of Pain. Cell labeling and the induction of CP were performed as previously described (22,35). The tracer was injected before a pancreatic duct infusion of TNBS or vehicle.…”

Effect of emodin on pancreatic fibrosis in rats

“…A chronic pancreatitis model was induced in rats by infusion of TNBS into the pancreatic duct with a modification of the method www.wjgnet.com described by Puig-Divi et al [8] (except for normal group). After fasted for 3 d, the rats in group 1 (normal group, nonoperation) and group 2 (control group, nontreating) received oral 0.9% sodium chloride solution.…”

Progression of Pancreatitis Prior to Diabetes Onset in WBN/Kob-Leprfa Rats

“…Pancreatitis is inflammation of the pancreas introduced by autodigestion and results in leakage of digestive enzymes. In rats and mice, experimental pancreatitis can be induced by ethanol feeding, [30] arginine injection, [11] and trinitrobenzene sulfonic acid (TNBS) infusion [23]. Extensive pancreatic damage, which likely results from chronic pancreatitis, is responsible for the development of diabetes.…”