The effect of Glycyrrhizin against Bothrops jararacasnake venom: Evaluation in vivoof Pro-Hemostatic Activities

Assafim, M.; Ferreira, M. S.;  Monteiro, R. Q. & Zingali, R. B

Departamento de Bioquímica Médica, ICB, CCS, Universidade Federal do Rio de Janeiro

Bothropsjararaca venom contains a number of proteins that interfere with the hemostatic system including pro- and anticoagulant as well as pro- and anti-platelet aggregating components., leading to an important coagulopathy hemorrhage and hematuria after bite accidents. We have established a venous thrombosis model in rats induced by B. jararaca venom administration. Intravenous administration of 100 g/kg of venom combined with stasis caused 100% of thrombus incidence (10.9 ± 1.3 mg). This new methodology allows the study of the potentially antiophidic compounds. In the present work we studied the effects of glycyrrhizin (GL), a previously described thrombin inhibitor, and antivenom for the treatment of Bothrops in this model. Intravenous administration of GL doses of 180 mg/kg body weight produced a significant inhibition of 86.5% (1.5 mg + 1.0 mg thrombus weight). Also, a antivenom dose of 27 l/kg produced a significant inhibition of 65 % (3.9 mg + 0.2 mg thrombus weight) on the thrombus formation induced by venom. In contrast, co-administration of 40 mg/kg of GL with 3 l/kg of antivenom decreased thrombus weight by 75% (2.5 ± 0.7 mg). Interestingly, we also observed that GL was able to decrease (1.5-fold) the hemorrhage induced snake venom and completely abolished hematuria.  On the other hand antivenom increased (5-fold) the hemorrhage but completely abolished hematuria. Preliminary aPTT and PT results ex vivo showed an activity of GL doses (180 mg/kg) and antivenom doses (27 l/kg) against the B. jararaca venom (100 mg/kg). Altogether, data indicate that GL was able to inhibit the venom effect showing potential antiophidic activity.

Financial Support: FAPERJ, IFS, CNPq, FINEP.

Correspondence to: assafim@bioqmed.ufrj.br or lzingali@bioqmed.ufrj.br