A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C

Qi, Jie-zhen; Lin, Xiao; Chen, Jiashu; Huang, Zhenhua; Qiu, Pengxin; Yan, Guiyun

doi:10.1016/j.bcp.2012.06.011

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…At 2, 4 and 6 h after the start of infusion, each rabbit was given 30 mg, i.p., sodium pentobarbital in 1 mL. The DIC experimental models were created as described previously; briefly, DIC was induced by infusion of an LPS solution (0.5 mg/kg LPS in 60 mL of saline) at a speed of 10 mL/h through the ipsilateral marginal ear vein over a period of 6 h.…”

Section: Methodsmentioning

confidence: 99%

“…Although many properties of Sal B have been exploited, there have been few studies into its effects against DIC. In previous studies, we established a rabbit model of lipopolysaccharide (LPS)‐induced DIC to explore the pharmacological effects of different drugs, such as tanshinone IIA, quercetin and fibrinogenase from Agkistrodon acutus venom, against DIC by examining the classical indices of the condition, including the activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count, protein C concentrations, fibrin–fibrinogen degradation products (FDP) and TNF‐ α . In the present study, we investigated the antagonism of Sal B of LPS‐induced DIC in rabbits through its inhibition of inflammatory factors and improvement of anticoagulation activity against thrombosis.…”

Section: Introductionmentioning

confidence: 99%

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Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

Bai

et al. 2014

Clin Exp Pharma Physio

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The aim of the present study was to investigate the effects of salvianolic acid B on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits. Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h) through the contralateral marginal ear vein. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration were determined, as were plasma levels of fibrin-fibrinogen degradation products (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)-α concentration. The gradual impairment of haemostatic parameters was induced by continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and plasma TNF-α and marked decreases in the platelet count, fibrinogen, FDP, protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF-α and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced by LPS infusion. These observations indicate that salvianolic acid B has an effect against LPS-induced DIC in rabbits.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

Bai

et al. 2014

Clin Exp Pharma Physio

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“…Previously, a novel fibrinolytic enzyme (FII), a metal-proteinase with a molecular weight of 26 000 and isoelectric point of 4.6, was purified from Agkistrodon acutus, a five pace snake in Anhui province of China, snake venom 17,18 . A former study showed that the dosage of FII in vivo could reach 5 mg/kg without hemorrhage 17 , and recent studies demonstrated that FII showed anti-DIC effect by degrading fibrinogen and dissolves micro-thrombosis in vivo 19,20 . Moreover, it was found out that FII could activate protein C, which plays a vital part in antiinflammation both in vivo and in vitro 20 .…”

Section: Introductionmentioning

confidence: 99%

A novel fibrinogenase fromAgkistrodon acutusvenom protects against LPS-induced endotoxemiaviaregulating NF-κB pathway

Wang

Qin

Shen³

et al. 2015

Immunopharmacology and Immunotoxicology

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“…Protac, a toxin extracted from the snake venom Agkistrodon contortix contortix , was discovered in 1985181920 and remains the gold standard for detection and quantification of PC in human plasma. Since then, other PC activators have been isolated from snake venoms but their activity is often promiscuous21. Furthermore, snake venoms find no use in clinical practice due to scarce availability, toxicity and allergenic properties.…”

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confidence: 99%

Rational Design of Protein C Activators

Barranco-Medina

Murphy

Pelc

et al. 2017

Sci Rep

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In addition to its procoagulant and proinflammatory functions mediated by cleavage of fibrinogen and PAR1, the trypsin-like protease thrombin activates the anticoagulant protein C in a reaction that requires the cofactor thrombomodulin and the endothelial protein C receptor. Once in the circulation, activated protein C functions as an anticoagulant, anti-inflammatory and regenerative factor. Hence, availability of a protein C activator would afford a therapeutic for patients suffering from thrombotic disorders and a diagnostic tool for monitoring the level of protein C in plasma. Here, we present a fusion protein where thrombin and the EGF456 domain of thrombomodulin are connected through a peptide linker. The fusion protein recapitulates the functional and structural properties of the thrombin-thrombomodulin complex, prolongs the clotting time by generating pharmacological quantities of activated protein C and effectively diagnoses protein C deficiency in human plasma. Notably, these functions do not require exogenous thrombomodulin, unlike other anticoagulant thrombin derivatives engineered to date. These features make the fusion protein an innovative step toward the development of protein C activators of clinical and diagnostic relevance.

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A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C

Cited by 6 publications

References 31 publications

Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

A novel fibrinogenase fromAgkistrodon acutusvenom protects against LPS-induced endotoxemiaviaregulating NF-κB pathway

Rational Design of Protein C Activators

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