The antithrombotic and haemostatic effects of LASSBio-752: a synthetic, orally active compound in an arterial and venous thrombosis model in rats

Author:

Frattani Flávia S1,Lima Lidia M2,Barreiro Eliezer J2,Zingali Russolina B3ORCID

Affiliation:

1. Laboratório de Hemostasia e Trombose – LHT, Departamento de Análises Clínicas e Toxicológicas - DACT, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil

2. Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), ICB-CCS, Cidade Universitária, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil

3. Instituto de Bioquímica Médica-CCS- UFRJ, Rio de Janeiro, RJ, Brazil

Abstract

Abstract Objectives In this work, we further investigated the effect of the compound LASSBio-752 in thrombosis models in rats. Methods Arterial and venous thrombosis model, ex-vivo recalcification time and aPTT and PT. Key findings In the venous thrombosis model, oral administration of LASSBio-752 [48.2 mg (100 μmol)/kg] one hour before the thrombus induction decreased thrombus weight by 37 ± 0.2%. Interestingly, the antithrombotic action of this compound [48.2 mg (100 μmol)/kg] occurred at 87.5 ± 2.1% of inhibition after 24 h of administration and showed a lasting activity. When tested on the arterial thrombosis model, after a 1-h interval, there was already an increase in time to total occlusion of 34 ± 2.4 min, but the greatest effect was observed at intervals between 6 and 15 h of administration, when no occlusion of the artery was observed. The antithrombotic effect was reduced after 24 h when the occlusion time was 23.8 ± 2.3 min, close to that of the control, 17.6 ± 2.0 min. We also observed that bleeding was not excessive in any of the intervals tested. Conclusions Our results indicate that compound LASSBio-752 is a potential candidate for utilization in the treatment of thromboembolic diseases.

Funder

CAPES

CNPq

FAPERJ

CT-INFRA-FINEP

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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