Isolated biomolecules of pharmacological interest in hemostasis from Cerastes cerastes venom

Abstract

Biomolecules from Cerastes cerastes venom have been purified and characterized. Two phospholipases isolated from Cerastes cerastes venom share 51% of homology. CC2-PLA2 exhibits antiplatelet activity that blocks coagulation. CCSV-MPase, a non-hemorrhagic Zn2+-metalloproteinase, significantly reduced the plasmatic fibrinogen level and hydrolyzes only its Bβ chain. Serine proteinases such as RP34, afaâcytin and CC3-SPase hydrolyze the fibrinogen and are respectively α, αβ and αβ fibrinogenases. In deficient human plasma, afaâcytin replaces the missing factors VIII and IX, and activates purified human factor X into factor Xa. It releases serotonin from platelets and directly aggregates human (but not rabbit) blood platelets. RP34 proteinase also had no effect on both human and rabbit blood platelet aggregation. CC3-SPase revealed a pro-coagulant activity. However, the insolubility of the obtained clot indicates that CC3-SPase does not activate factor XIII. In addition, CC3-SPase clotting activity was carried out with human plasmas from volunteer patients deficient in clotting factors. Results showed that CC3-SPase shortens clotting time of plasma deficient in factors II and VII but with weaker clotting than normal plasma. The clotting time of plasma deficient in factor II is similar to that obtained with normal plasma; suggesting that CC3-SPase is able to replace both factors IIa and VII in the coagulation cascade and thus could be involved in the blood clotting process via an extrinsic pathway. These results imply that CC3-SPase and afaâcytin could repair hemostatic abnormalities and may replace some factors missing in pathological deficiency. Afaâcytin also exhibits α fibrinase property similar to a plasmin-like proteinase. Despite its thrombin-like characteristics, afaâcytin is not inhibited by plasmatic thrombin inhibitors. The procoagulant properties of afaâcytin might have potential clinical applications.

Pathophysiological and Pharmacological Effects of Snake Venom Components: Molecular Targets

“…Snake venoms are rich bio-resource of biologically active compounds, but only one percent of these molecules have been characterized; therefore, many of the bioactive components remain to be explored. These biomolecules present diverse activities which could also be used as tools mainly for medical research or diagnosis [9][10][11]. Identification and characterization of toxic compounds present in snake venoms are the main step not only to understand the pathophysiological changes observed after bites, but they can also be useful to improve the treatment after snake bites.…”

“…Snake venoms and mainly those of Viperidae contain also molecules that act on the four interconnected blood systems as producers of inflammatory mediators, (i) coagulation system, (ii) fibrinolysis, (iii) complement and (iiii) kinin system ( Figure 2) [17]. [9][10][11]20,21,24,25].…”

“…It was reported that Promutoxin (R49sPLA2) isolated from the venom of Probothrops muscrosquamatus , induced a release of IL-12, TNF-α, IL-6 and IL-1β from a cell culture of human monocytes and IL-2 cytokines, TNF and IL-6 from human T lymphocytes. Some SV-PLA2s hydrolyze membrane phospholipids of platelets, leading to the release of agonists, mainly arachidonic acid a precursor of several inflammatory substances such as prostaglandins and leukotrienes [9,11]. Activation of the complement system results in the formation of many additional degradation products that serve as important mediators of inflammation.…”

Antiplatelet and anticoagulant activities of two phospholipase A2s purified from Cerastes cerastes venom: Structure‐function relationship

“…The PLA 2 s of Cerastes cerastes induce hemolysis, anticoagulation, myotoxicity, and platelet effects . These effects associated to those of other components of snake venoms are responsible for pathophysiological alterations due to snake bite . C. cerastes venom is rich in both enzymatic and nonenzymatic components from which only a weak number has been characterized.…”

A Study of Cardiac Profile in Patients with Snake Envenomation and Its Complications

“…Hemorrhagins are present mainly in Echis carinatus. Haemorrhage, shock and acute renal failure are the main causes of death in cases of elapide bite [4] [5]. Cardiotoxicity is also seen in many cases dying of severe viper bite.…”