A Severe Acute Pancreatitis Mouse Model Transited from Mild Symptoms Induced by a “Two-Hit” Strategy with L-Arginine

Abstract

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.

Novel Amphibian Bowman–Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice

“…The effect of Ranacin on AP was tested in l -Arg-induced mice as previously reported by Yang.et al with slightly modified . As shown in Figure A,B, the l -Arg administration significantly augmented serum amylase activity, which is a key indicator of pancreatic acinar cell injury, and IL-6, which is a marker of the systemic inflammatory response.…”

“…The effect of Ranacin on AP was tested in L-Arg-induced mice as previously reported by Yang.et al with slightly modified. 29 As shown in Figure 2A,B, the L-Arg administration significantly augmented serum amylase activity, which is a key indicator of pancreatic acinar cell injury, and IL-6, which is a marker of the systemic inflammatory response. However, Ranacin and Nacetylcysteine (NAC) significantly reduced serum amylase and IL-6 levels in a concentration-dependent manner compared to the untreated AP group (Figure 2A,B).…”

Silymarin attenuates escitalopram (cipralex) induced pancreatic injury in adult male albino rats: a biochemical, histological, and immunohistochemical approach

“…Moreover, there is an evident highly significant decrease ( P <0.001) of PW/RW ratio in cipralex group than control group, that was synchronous with the decreased pancreatic index after the second hit of induced sever AP by L-arginine [ 43 ], that explained by serious destruction and a self-digestion of the pancreatic tissue [ 44 ].…”

Heparin Protects Severe Acute Pancreatitis by Inhibiting HMGB-1 Active Secretion from Macrophages

“…The mouse model was set up according to the published paper [15]. L-arginine solution (8% w/w, pH = 7.4) was incubated in ice-cold water and injected intraperitoneally into the mice twice at an interval of one hour, with each dosage of 4 g/kg (approximately 1.3 mL).…”

“…The pathological slices were scanned and recorded on a Pannoramic SCAN II instrument (3D Histech, Budapest, Hungary). Two investigators who were blind to the experimental treatment scored the pancreatic necrosis degree according to the published scoring standards [15]. TUNEL staining was performed according to the manufacturer's instructions (KeyGEN Biotech, Nanjing, China).…”