Table 1.

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Model	Advantages	Disadvantages	Translational Medicine
Non-Invasive models
Cae-induced or Hormone-Induced	The cerulein (Cae) model is among several animal models of experimental acute pancreatitis (AP) Suitable for investigating pathogenesis and cellular changes in early phases of AP The advantages are noninvasiveness, low cost, rapid induction, high reproducibility, and broad applicability	The induction of acute pancreatitis is performed by several injections Does not mimic severe form of human AP	Exhibit biochemical, morphological, and pathophysiological similarities to various aspects of human pancreatitis [31] Cae pancreatitis is like human edematous pancreatitis, manifesting with dysregulation of digestive enzyme production and cytoplasmatic vacuolization[31, 32]
Alcohol	The alcohol-induced model could be performed via intravenous, oral, intraperitoneal, and intraductal administration Alcohol increases pancreatic duct permeability, decreases pancreatic blood flow and microcirculation, diminishes pancreatic oxygen consumption, and induces oxidative stress	The morphology of the AP varies according to the animal model, the dose of ethanol administration, and the pre-sensitization agents used Acute pancreatitis induced by alcohol alone has been challenging to achieve and requires prior sensitization with other factors, such as exocrine hyperstimulation, to allow significant pancreatic damage to occur, so allows study of alcohol’s role in predisposing to AP	Alcohol is one of the major etiologic factors of acute pancreatitis [52] Allows studying the effect of toxic metabolites derived from oxidative and non-oxidative metabolism
Hypertriglyceridemia (HTG)	Models for establishing inducible HTG-AP must be induced through the diet	The TG levels will fluctuate with time after the model has been established	Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the second major cause of acute pancreatitis [73] HTG-AP that can mimic the physiological, histological, and clinical features of human HTG-AP [75]
Diet-Induced	Mimics severe human pancreatitis Choline-deficient diet diet has been associated with the activation of intrapancreatic proteases and characteristic vascular changes	Costly diet Requires standardization and careful monitoring of diet intake Depends critically on the sex, age, and weight of the mice Variation among animals could be high, making using many animals in each group necessary for meaningful results	This diet model is particularly suitable for studying the potential for new therapeutic substances as CDE diet-induced pancreatitis shares many characteristics with severe human acute pancreatitis [94]
Basic Amino Acid-Induced	Highly reproducible The degree of severity could be controlled as it depends upon the dose of arginine and time of exposure Interstitial edema, neutrophil infiltration, acinar cell degranulation, and elevated amylase are observed when arginine is administrated in low doses L-ornithine are simple, noninvasive, reproducible model of acute necrotizing pancreatitis by intraperitoneal injection L-lysine administration causes early pancreatic mitochondrial damage that impairs the ATP synthase activity of pancreatic mitochondria L-lysine model is economical and reproducible	Higher doses (7.5 g/kg) of L-arginine can be lethal for experimental animals, whereas a 2.5 g/kg dose only causes mild pancreatic injury L-arginine model its lack of clinical relevance AP caused by amino acid overdose is rare in humans	L-ornithine showing typical laboratory and morphologic signs observed in the human disease [96]
Invasive models
Pancreatic Duct Ligation (PDL)	Mimicks gallstone-induced AP The surgical manipulation is simple, requiring either ligation of the common biliopancreatic duct Early changes in the duct can be observed at 1–5 h after ductal ligation, and 24 and 48 h findings such as pancreatic edema, inflammatory cell infiltration, and hyperamylasemia This cell model could identify acinar cell necrosis as the early point of injury in acute necrotizing pancreatitis	The complexity, technical difficulty, high cost, limited reproducibility, and the analogy to chronic pancreatitis have made the duct ligation model infrequently used for investigating AP	The duct obstruction model mimics gallstone obstruction-induced AP in the clinical setting. [22] This model mimics gallstone obstruction-induced AP with high mortality; thus, it could be used to investigate the pathogenesis of severe AP and test new therapies [45] Gallstone obstruction is the major etiologic factor of acute pancreatitis [121]
Bile Acid Salts-Induced	Short period needed to induce severe necrosis Impaired intestinal permeability, bacterial translocation, the perturbation of energy metabolism in the intestinal wall, pulmonary endothelial barrier dysfunction, microvascular endothelial barrier dysfunction, activation of mast cells, induction of nitric oxide synthase, increased catalytic activity of phospholipase A, increased cytokine levels and increase myeloperoxidase activity Is a model of locally induced pancreatic damage without systemic action of the pancreatitis-inducing agent	Requires abdominal incision and expertise in cannula insertion The experimental animals'mortality depended on the injected taurocholate concentration	Biliary calculous is the most common cause of AP and is associated with significant morbidity and mortality [121] Intraductal injection of Na-TC into the rat pancreas causes a disease with gross and histopathological changes that correspond to those seen in human pancreatitis [129]
Cholangiopancreatography (ERCP)	Is based on high pressure (50 mm Hg) of contrast agent intraductal injection produced histology alteration, edema, myeloperoxidase activity, and hemorrhage Endoscopic retrograde cholangiopancreatography (ERCP) is a specialized endoscopic procedure for managing pancreaticobiliary disorders	This model is very invasive and difficult to carry out Expensive	Post-ERCP pancreatitis (PEP) is one of the most frequent complications of ERCP, with an incidence of 1.5 to 15% [145]
Ischemia/Reperfusion model	It induces a partial blocking of the arterial blood supply within the pancreas Ischemia/reperfusion causes an inflammatory reaction, as observed in AP	The severity of changes depends on the duration of ischemia and the duration of reperfusion	Clinical and experimental studies have shown that ischemic injury plays an important part in the pathogenesis of acute pancreatitis [144.145]