Pharmacologic evaluation of factor XIIIa*-like enzyme activity in equine plasma as a potential therapeutic avenue for the inhibition of fibrinous tissue.

This research evaluates various pharmaceutical compounds for their potential to inhibit a specific enzyme correlated with blood clotting in horse plasma, suggesting possible therapeutic applications in managing fibrin-based tissue formation.

Objective and Methodology

• The study’s main objective was to assess several pharmaceutical compounds to see if they could selectively inhibit the activity of the enzyme known as factor XIIIa* which gets activated during blood clotting.
• The experiment used pooled equine (horse) plasma, where the presence of the enzyme activity was confirmed through specific assay procedures.
• The assays involved a process where a fluorescent compound named monodansylcadaverine was incorporated into purified casein (a protein).

Testing Procedure and Recognition of Pharmaceuticals

• The pharmaceuticals that could inhibit the function of the enzyme were identified by the formation of plasma gel with high transparency, which corresponded to high spectrophotometric transmittance.
• Transparent fibrin gels’ solubility in concentrated urea solution, coupled with the simultaneous reduction of native fibrinogen fractions and the production of fibrin monomer, confirmed the inhibition.

Anticoagulants and Non-Inhibiting Compounds

• Pharmaceuticals acting primarily as anticoagulants were distinguished by the absence of plasma gel formation, alongside high spectrophotometric transmittance and no detectable depletion of native fibrinogen fractions.
• Compounds that failed to suppress the transformation process from fibrinogen to fibrin, known as coagulation, were identified by the resulting opaque plasma gels caused by fibrin polymerization, low spectrophotometric transmittance values, and the simultaneous depletion of native fibrinogen fractions.

Classification of Inhibitory Pharmaceuticals

• The research further classified the inhibitors of the factor-XIIIa* enzyme activity into two categories based on their activity in the transglutamination process.
• These classifications were the competitive inhibitors of phase 1 (carbamide) or phase 2 (terminal amine), which offer unique avenues for therapeutic application.