Counteracting effect of glycyrrhizin on the hemostatic abnormalities induced by Bothrops jararaca snake venom

Abstract

1 Envenomation by the snake Bothrops jararaca is typically associated with hemostatic abnormalities including pro-and anticoagulant disturbances. Glycyrrhizin (GL) is a plant-derived thrombin inhibitor that also exhibits in vivo antithrombotic properties. Here, we evaluated the ability of GL to counteract the hemostatic abnormalities promoted by B. jararaca venom. 2 GL inhibited the human fibrinogen clotting (IC 50 ¼ B1.0 mg ml; 0.47 mM) and platelet aggregation (IC 50 ¼ B0.28 mg ml À1 ; 0.33 mM) induced by B. jararaca venom, in vitro. 3 The in vivo effect of GL was tested in rats using a model of venous thrombosis in which intravenous (i.v.) administration of B. jararaca venom (100 mg kg À1 ) produced in all animals a thrombus with a mean weight of 10.671.7 mg. 4 Prior administration of GL (180 mg kg À1 ) or antibothropic serum (27 ml kg À1 ) inhibited thrombus formation by 86 and 67%, respectively. Remarkably, co-administration of ineffective doses of GL and antibothropic serum markedly decreased thrombus weight, suggesting a synergistic effect. 5 Co-administration of GL 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 GL, antibothropic serum or both before venom administration efficiently prevented this abnormality.6 Altogether, we demonstrate here that GL prevents both in vitro and in vivo venom-induced changes in hemostasis, suggesting a potential antiophidic activity.

<I>IN VIVO</I> NEUTRALIZATION OF <I>NAJA NIGRICOLLIS</I> VENOM BY <I>UVARIA CHAMAE</I>

“…However, in most cases, scientific evidence of their antiophidian activity is still needed. The exact mechanisms of action of ;the plant extracts remain largely illusive, however, a number of previous reports indicate that plant-derived compounds, such as rosmarinic acid Aang et al, 2010) quercetin (Nishijima et al, 2009) and glycyrrhizin (Assafim et al, 2006) can inhibit biological activities of some snake venoms invivo and invitro.…”

Effects of Ethanolic Leaf Extract of Euphorbia hirta on Snake Venom Induced Toxicity in Mice

“…Although anti-venom (which is prepared from animal sera) immunotherapy is the only treatment available against snake envenomation, it is associated with many side effects which include; anaphylactic shock, pyrogen reaction and serum sickness. These are possible outcomes of the action of antigenic proteins present in higher concentrations in anti-venom (Assafim et al, 2006). Also, antivenom (anti sera) do not neutralize the local tissue damage (Gutierrez et al, 2009), are not available in remote areas and are quite expensive.…”

“…These are possible outcomes of the action of antigenic proteins present in higher concentrations in anti-venom (Assafim et al, 2006). In addition, they do not neutralize the local tissue damage (Gutierrez et al, 2009).…”

ANTI-VENOM STUDIES ON <i>OLAX VIRIDIS</i> AND <i>SYZYGIUM GUINEENSE</i> EXTRACTS

“…In many countries, plant extracts have long been in use traditionally to treat envenomation (Mors et al, 2000). The exact mechanisms of action of the plant extracts remain largely illusive, however, a number of previous reports indicate that plant-derived compounds such as rosmarinic acid (Ticli et al, 2005;Aung et al, 2010), quercetin (Nishijima et al, 2009) and glycyrrhizin (Assafim et al, 2006) can inhibit biological activities of some snake venoms in vivo and in vitro.…”