Abstract

Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed at treating newly formed blood clots. Aged clots are stabilized by a large number of isopeptide bonds that prevent the action of thrombolytics. These bonds are destroyed by destabilase, an enzyme of the leech’s salivary glands. Here, we conducted a pilot study to evaluate the feasibility and effectiveness of the use of destabilase in relation to blood clots formed during real pathological processes. We evaluated the isopeptidase activity of destabilase during the formation of a stabilized fibrin clot. We showed that destabilase does not affect the internal and external coagulation cascades. We calculated the dose–response curve and tested the ability of destabilase to destroy isopeptide bonds in natural blood clots. The effect of aged and fresh clots dissolving ability after treatment with destabilase coincided with the morphological characteristics of clots during surgery. Thus, recombinant destabilase can be considered as a potential drug for the treatment of aged clots, which are difficult to treat with known thrombolytics.

Highlights

  • IntroductionThe mechanism of their action is to catalyze the proteolytic degradation of polypeptide bonds in the fibrin polymer molecules, which form the basis of a blood clot

  • We determined isopeptidase activity of recombinant destabilase by monitoring the ability of the unstabilized fibrin to dissolve in the 5% monochloroacetic acid

  • This assay shows the concentration of factor XIII at which a stabilized fibrin clot does not form and dissolves in monochloroacetic acid

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Summary

Introduction

The mechanism of their action is to catalyze the proteolytic degradation of polypeptide bonds in the fibrin polymer molecules, which form the basis of a blood clot

Methods
Results
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