Gabexate Mesylate-Poloxamer 407 Conjugate Alleviates Sodium Taurocholate-Induced Severe Acute Pancreatitis in an Optimized Rat Model.

BACKGROUND AND AIMS

We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model.

METHODS

An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas.

RESULTS

SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats.

CONCLUSIONS

Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.