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-α) 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-αin 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 rFII as well as Infliximab. Furthermore, rFII inhibited TNF-α secretion by rat peritoneal macrophages in a time- and concentration-dependent manner but didn't influence interleukin (IL) -1β secretion in vitro. The degradation potency of rFII for human TNF-α was greater than that for rat TNF-α. Our findings suggest that rFII could have protective effect on taurocholate-induced SAP in rats, mainly depending on direct degradation of TNF-α.
Luo
Sen
S
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, Guangdong 510080, PR China.
Wang
Rongrong
R
Jiang
Weijian
W
Lin
Xi
X
Qiu
Pengxin
P
Yan
Guangmei
G
D017836:Agkistrodon; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation; D000069285:Infliximab; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D045726:Metalloproteases / Q000494:pharmacology* / Q000627:therapeutic use; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012910:Snake Venoms / Q000201:enzymology*; D015996:Survival Rate; D013656:Taurocholic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D020011:Protective Agents; D011994:Recombinant Proteins; D012910:Snake Venoms; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D000069285:Infliximab; D045726:Metalloproteases