title: Ability of a synthetic coumestan to antagonize Bothrops snake venom activities.
abstract: We investigated a synthetic coumestan named LQB93 and similar compounds abilities to antagonize activities of Bothrops jararacussu and Bothrops jararaca crude venoms in different protocols. The antimyotoxic activity was evaluated in vitro by the rate of release of creatine kinase (CK) from isolated mouse extensor digitorum longus muscle (EDL) induced by B. jararacussu (25 g/ml). For in vivo studies, B. jararacussu venom (1.0 mg/kg) was preincubated with LQB93 (0.1-30 mg/kg), during 30 min, for later injection in mouse tight and evaluation of the antimyotoxic and anti-edematogenic effects. LQB93 antagonized in vitro, the increase of CK release from the EDL muscle (IC(50)=0.0291 M). It also showed in vivo, antimyotoxic and anti-edematogenic effects that were dose-dependent with ID50 of 0.17 mg/kg and 0.14 mg/kg, respectively. The hemorrhage induced by B. jararaca (1.0 mg/kg) venom in the mouse skin, was abolished by LQB93 (10.0 mg/kg) preincubated with venom. Like wedelolactone, LQB93 protected rat isolated heart on a Langendorff preparation, from the cardiotoxicity of B. jararacussu venom. LQB93 inhibit the effects of Bothrops venoms like wedelolactone, a natural compound isolated from the plant Eclipta prostrata.
authors.affiliation: Departamento de Farmacologia Básica e Clínica - ICB, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil. pamelo@farmaco.ufrj.br
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
authors.forename: Diogo A
authors.initials: DA
authors.lastname: Pinheiro
authors.forename: Hilmar Dias
authors.initials: HD
authors.lastname: Ricardo
authors.forename: Fabrício F A
authors.initials: FF
authors.lastname: Fernandes
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Tomaz
authors.forename: Camila Z
authors.initials: CZ
authors.lastname: El-Kik
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Strauch
authors.forename: Tatiane F
authors.initials: TF
authors.lastname: da Fonseca
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Sifuentes
authors.forename: Sabrina
authors.initials: S
authors.lastname: Calil-Elias
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Buarque
authors.forename: Flávia V
authors.initials: FV
authors.lastname: Brito
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.forename: Alcides J M
authors.initials: AJ
authors.lastname: Da Silva
mesh_terms: D000818:Animals; D017837:Bothrops / Q000502:physiology*; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D003375:Coumestrol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D003402:Creatine Kinase / Q000032:analysis / Q000378:metabolism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D006321:Heart / Q000187:drug effects; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010447:Peptide Hydrolases / Q000032:analysis; D010740:Phospholipases / Q000032:analysis; D051381:Rats
chemical_list: C545723:8-methoxycoumestrol; D003374:Coumarins; D003435:Crotalid Venoms; D003402:Creatine Kinase; D010740:Phospholipases; D010447:Peptide Hydrolases; C505898:coumestan; D003375:Coumestrol