XXXV Reunião Anual da SBBqResumoID:9259


COUTERACTING EFFECT OF GLYCYRRHIZIN ON THE HAEMOSTATIC ABNORMALITIES INDUCED BY BOTHROPS JARARACA SNAKE VENOM


Mariane Assafima, Marcos S. Ferreiraa, Flávia S. Frattania, Jorge A. Guimarãesb, Robson Q. Monteiroa and Russolina B. Zingalia*1



aInstituto de Bioquímica Médica, Programa de Biologia Estrutural, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro,  Brasil; bCentro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.


Envenomation by the snake Bothrops jararaca is typically associated with haemostatic abnormalities including pro- and anticoagulant disturbances. Glycyrrhizin is a plant-derived thrombin inhibitor that also exhibits in vivo antithrombotic properties. Here, we evaluated the ability of glycyrrhizin to counteract the haemostatic abnormalities promoted by B. jararaca venom. Glycyrrhizin inhibited the human fibrinogen clotting (IC50= ~1.0 mg/mL) and S-2238 hydrolysis (IC50 = ~0.4  mg/mL) induced by B. jararaca ven om, in vitro. The in vivo effect of glycyrrhizin was tested in rats using a model of venous thrombosis in which i.v. administration of B. jararaca venom (100 μg/kg) produced in all animals a thrombus with a mean weight of 10.6 ± 1.7 mg.  Prior administration of glycyrrhizin (180 mg/kg) or antibothropic serum (27 μL/kg) inhibited thrombus formation by 86% and 67%, respectively. Remarkably, co-administration of ineffective doses of glycyrrhizin and antibothropic serum markedly decreased thrombus weight, suggesting a synergistic effect. Co-administration of glycyrrhizin with antibothropic serum abolished venom-induced bleeding. Ex vivo clotting times showed that rat plasma was non-clotting after i.v. administration of B. jararaca venom. Treatment with glycyrrhizin, antibothropic serum or both prior to venom administration efficiently prevented this abnormality. Altogether, we demonstrate here that glycyrrhizin prevents both in vitro and in vivo venom-induced changes in haemostasis, suggesting a potential antiophidic activity. Most strikingly, glycyrrhizin exhibited a synergistic effect with antibothropic serum, thus demonstrating that new alternative compounds could be associated with conventional antiserum therapy.

Financial support: CAPES, CNPq, FAPERJ