Counteracting effect of glycyrrhizin on the hemostatic abnormalities induced by Bothrops jararaca snake venom.
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 (IC50 = approximately 1.0 mg ml(-1); 1.2 mM), H-D-phenylalanyl-L-pipecolyl-L-arginine-p-nitroanilide dihydrochloride hydrolysis (IC50 = approximately 0.4 mg ml(-1); 0.47 mM) and platelet aggregation (IC50 = approximately 0.28 mg ml(-1); 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 microg kg(-1)) produced in all animals a thrombus with a mean weight of 10.6+/-1.7 mg. 4. Prior administration of GL (180 mg kg(-1)) or antibothropic serum (27 microl kg(-1)) 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.
Assafim
Mariane
M
Instituto de Bioquímica Médica, Programa de Biologia Estrutural, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Ferreira
Marcos S
MS
Frattani
Flávia S
FS
Guimarães
Jorge A
JA
Monteiro
Robson Q
RQ
Zingali
Russolina B
RB
D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D017837:Bothrops; D003435:Crotalid Venoms / Q000506:poisoning*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006470:Hemorrhage / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D020246:Venous Thrombosis / Q000188:drug therapy
D000997:Antivenins; D003435:Crotalid Venoms; D019695:Glycyrrhizic Acid