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J. Venom. Anim. Toxins incl. Trop. Dis. Vol.9, No.2, p.328, 2003. Conference - ISSN 1678-9199. |
(1)Departamento de Farmacologia Básica e Clínica, ICB, UFRJ. Rio de Janeiro RJ. 21941-590, Brazil
Some previous data from our laboratory so far obtained, indicated that extracts or purified constituents of plant Eclipta prostrata(EP) are effective in the prevention of the myotoxicity of crotalid snake venoms. As part of a program aimed at synthesizing biologically active flavonoids, some coumestans bearing different patterns of oxygenation at rings A and D were chosen as target molecules, synthesized for the first time and their action as antimyotoxic compared with that observed for wedelolactone (W) aEP constituent. We mainly tested a coumestan named PCALC36, which at0,1-10 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 mcg/g b.w.). Also, this coumestanat 3 mcg/g neutralized at the same dose the venoms of Agkistrodon contortrix laticinctus and Crotalus viridis viridis by 50% and 70% respectively, and reduced the myotoxicity of BthTX-I and BthTX-II by 35% and 75%. Also we have shown that heparin and other polyanions inhibit the myotoxic effect of Bothrops venoms by formation of acid-base complexes with the basic myotoxins. Electron microscopy studies show that heparin treatments promoted a good muscle regeneration, with the organization of regenerated fibers being similar to the control while the animals that did not receive any treatment exhibited a complete disorganization of muscle cells. These data indicate that heparin improves the regeneration of EDL muscle damaged by B. jararacussu venom.
Financial support: CAPES, FAPERJ, PRONEX (No. 41.96.0888.00), FUJB-UFRJ and CNPq.
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