L-arginine (or Secretagogue (Caerulein)) acute pancreatitis models in rats.
L-arginine as a substrate for neuronal, inducible, and endothelial nitric oxide synthase, widely used in therapy. The L-arginine dose may vary depending on the required severity of pancreatitis (amount of acinar cells died). Secretagogue increases protein-rich secretion of the pancreas (hyperstimulation). This leads up to a 75% reduction of the enzyme stores of the exocrine part of the pancreas and results in pancreatic injury.
The model progress is characterized by acute pancreatic inflammation accompanied by edema infiltration of leukocytes, capillary dilatation, and microfocal parenchyma necrosis.
A standard study design includes at least 3 groups of Wistar rats (vehicle dosed, treated with reference compound, and tested compound treated group), 5 rats per group, 7 days of acclimatization period, single or multiple L-arginine injections, 7 days of the treatment period. Animals are monitored for mortality, bodyweight control changes, and signs of toxicity daily for the duration of treatment and post-treatment period. Rats’ treatment procedures include invasive (by IV, IP, SC), and non-invasive (PO, and diet incorporated) routes of drug administration. Clinical chemistry parameters of pancreas pathology development (level of amylase, trypsinogen, lipase in blood) are determined over time (0, 2, 5, and 7 days after the administration of L-arginine). Gross necropsy is performed on all animals at the endpoint. Specific tests, such as hematological, urinary, and blood clinical chemistry analysis, food intake, histopathology, etc. in combination with specific endpoints are available on request.