ANTIVENOM EFFECT OF A NEW SYNTHETIC COUMESTAN ANALOG OF WEDELOLACTONE

Vianna-da-Silva, N.M.(1), Moraes, R.A.M. (1), da Silva, A.J.M. (2), Costa, P.R.R. (2), Melo, P.A. (1)

(1)Departamento de Farmacologia Básica e Clínica ICB, (2)Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro

We studied the anti-snake venom activity of a synthetic coumestan named PCALC36 by using in vitro assay and isolated muscle preparations. We evaluated the anti-hemorrhagic and the antimyotoxic effect of this substance in vivo on pre-incubation and pre-treatment protocols against some crotalid crude venoms as well as some isolated toxins. This substance at 0,1-10 micromolar reduced by 95% the rate of CK release induced by B. jararacussu (25 mcg/ml) in vitro from the mouse Extensor digitorum longus muscle (EDL). In vivo, the preincubation with PCALC36 (0,03-5 mcg/g b.w.) neutralized from 4 to 92% the myotoxic effect of B. jararacussu venom (1 micg/b.w.). Also, this coumestan at 3 mcg/g neutralized the venoms (1 mcg/g b.w.) of Agkistrodon contortrix laticinctus and Crotalus viridis viridis by 50% and 70%, respectively, and reduced the myotoxicity of Bothropstoxin I or II (2.5 mcg/g) by 35% and 75% respectively. PCALC36 (0.01-6 mcg/g b.w.) when pre-incubated with B. jararaca venom (1 mcg/g b.w.) abolished its hemorrhagic effect. Pre-treatments with PCALC36 (0,3-20 mcg/g b.w.) reduced about 45 and 75% the myotoxic and hemorrhagic effects of B. jararacussu and B. jararaca venoms. Above 90% of phospholipaseA₂ and proteolytic activities of B. jararacussu and B. jararaca venoms (10 mcg/ml) were inhibited by PCALC36 (3-400 micromolar). These data indicate that the coumestan PCALC36 is able to neutralize the main effects of the these studied viperid venoms, protecting the muscle cells from the sarcolemmal damage and preventing the hemorrhagic lesions.

Support: PRONEX (No. 41.96.0888.00), FAPERJ, FUJB-UFRJ and CNPq.

CORRESPONDENCE TO:

P.A. MELO, Departamento de Farmacologia Básica e Clínica, ICB, UFRJ. Rio de Janeiro RJ. 21941-590, Brazil, Email: pamelo@farmaco.ufrj.br