Novel recombinant fibrinogenase of Agkistrodon acutus venom protects against LPS-induced DIC.
BACKGROUND
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the widespread activation of coagulation. This leads to failure of multiple organs in the body and finally death. Because there is no effective therapy for DIC, the clinical prognosis is poor and the mortality is high.


METHODS
The animals were intravenously injected with Lipopolysaccharide (LPS) for 6 hours and simultaneously infected three doses of recombinant fibrinogenase II (rFII) for 2 hour. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelets count, fibrinogen and fibrin-fibrinogen degradation products (FDP) were determined. The plasma levels of alanine aminotransferase (ALT), creatinine (Cr) and tumor necrosis factor-alpha (TNF-alpha) were detected. Liver and kidney samples were stained with hematoxylin-eosin and kidney sections were stained with phosphotungstic acid-hematoxylin.


RESULTS
We observed that rFII increased survival rate in LPS-induced DIC rabbits as well as heparin did. Administration of rFII as well as heparin attenuated the increased plasma levels of APTT, PT and FDP and the decreased plasma level of fibrinogen at 6 h. rFII reduced hepatic and renal damages and decreased the levels of ALT and Cr as well as heparin did. rFII also significantly reduced the increased plasma levels of TNF-alpha. rFII significantly reduced the kidney fibrin deposits with respect to LPS treated animals.


CONCLUSIONS
Our findings suggest that rFII from Agkistrodon acutus venom could have protective effect on DIC via reducing liver and renal damages and direct degradation of microthrombi.
Wang
Rongrong
R
Department of Pharmacology, Zhong-shan Medical College, Sun Yat-sen University, Guangzhou, 510080, P.R. China.
Cai
Jinlian
J
Huang
Yijun
Y
Xu
Dong
D
Sang
Hanfei
H
Yan
Guangmei
G
D017836:Agkistrodon / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003435:Crotalid Venoms / Q000201:enzymology* / Q000235:genetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000473:pathology; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000494:pharmacology*
C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; C412879:venombin B