A novel recombinant snake venom metalloproteinase from Agkistrodon acutus protects against taurocholate-induced severe acute pancreatitis in rats

Severe acute pancreatitis (SAP) remains a challenging disease to manage, with high mortality, limited understanding of pathogenesis and lack of specific therapy. Recombinant fibrinogenase II (rFII) from Agkistrodon acutus venom has been found to degrade tumor necrosis factor-alpha (TNF-alpha) which is vital in mortality of SAP. Here we investigate the in vivo effects of rFII in rat SAP and confirm the degradation effect of rFII for TNF-alpha in vitro. The SAP model was prepared by retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct in male Sprague Dawley rats. Treatment with 1 mg/kg rFII could significantly increase survival rate of SAP rats (P = 0.006) as well as 8 mg/kg Infliximab treatment did. The pancreatic and pulmonary injury and the peritoneal and systemic inflammatory response were also attenuated by rFll as well as lnfliximab. Furthermore, rFll inhibited TNF-alpha secretion by rat peritoneal macrophages in a time- and concentration-dependent manner but didn't influence interleukin (IL) -1 beta secretion in vitro. The degradation potency of rFll for human TNF-alpha was greater than that for rat TNF-alpha. Our findings suggest that rFII could have protective effect on taurocholate-induced SAP in rats, mainly depending on direct degradation of TNF-alpha. (C) 2010 Published by Elsevier Masson SAS.