Pharmacological Characterization Of The Mouse Paw Edema Induced By Bothrops Leucurus (White-Tailed Jararaca) Venom

Prianti-Jr, A.C.G.¹, Barbosa, A.M.¹, Labat, M.R.¹, Lopes-Martins, R.A.B.¹, Ribeiro, W.¹, Cogo, J.C.¹, Hyslop, S.²

1 Laboratório de Fisiologia e Farmacodinâmica, Instituto de Pesquisa e Desenvolvimento (IP&D), Universidade do Vale do Paraíba (UNIVAP), São José dos Campos, SP; 2 Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Bites by Bothrops leucurus, a species found in northeastern Brazil, cause local tissue damage that includes edema, hemorrhage and necrosis. In this work, we investigated the ability of B. leucurus venom to cause edema in mouse hind paws. The changes in paw volume following the intraplantar injection of venom (0.1, 0.25, 0.50 and  0.75 µg/paw) were measured by plethysmometry for up to 24 h after venom injection. B. leucurus venom caused dose- and time-dependent edema at all doses; hemorrhage was also seen at the two highest doses.  The edema was maximal after 1 h at low doses and after 3 h with high doses but disappeared after 24 h. Pretreating the mice (n=6) with  rofecoxib (10 mg/kg, orally, 2 h before venom) and indomethacin (4 mg/kg, i.v., 30 min before venom) (inhibitors of cyclooxygenase), cyproheptadine (6 mg/kg, i.p., 15 min before venom) (histamine H1 and serotonin 5-HT2 receptor antagonist), mepyramine (6 mg/kg, i.p., 15 min before venom) (histamine H1 receptor antagonist) and L-NAME (50 mmol/kg, 24 h before venom) (nitric oxide synthase inhibitor) significantly attenuated the venom-induced edema, when compared with the results of control (119.6±22.6) vs (38.2±16.7; 32.8±17.6; 37.2±9.9; 20.3±25.1; 49.6±19.9; respectible). Dexamethasone (0.2 mg/kg, i.m., 2 h before venom) (an indirect inhibitor of PLA2) (88.8±17.7) significantly inhibited the edema during the first hour after venom injection. These results show that B. leucurus venom causes edema in mouse paws and that this edema is mediated by nitric oxide, histamine and arachidonic acid metabolites formed by cyclooxygenases 1 and 2.

Correspondence to: prianti@univap.br