Estudo da trombose pulmonar causada pela peçonha da cascavel sul-americana (Crotalus durissus) e suas frações

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

Convulxin is a high molecular weight, non-enzymatic, platelet aggregating protein present in the venom of South American rattlesnake, Crotalus durissus terrificus. In this work, we investigatd the ability of convulxin to cause pulmonary thrombosis in mice after intravenous injection and examined the possible mechanism (s) involved using specific inhibitors. Convulxin was purified ftom C. d. cascavella e C. d terrificus venom by chromatography on Sephadex G-75 in 0.005 M ammonium formate, ph 3.5. Male Swiss mice were injected i.v. with varying doses of convulxin and then euthanized 30 minoLater after wich the lungs were rapidly removed, fixed and processed for histological analysis to determine the ftequency of pulmonary thrombosis. Human platelet-rich plasma was prepared by standart differential centrifugation. Convulxin from C. d cascavella e C. d terrificus venoms aggregated hurnan platelet at concentrations 8 ng/ml and cause pulmonary thrombosis at doses20 ~g/kg. The latter was dose-dependent at doses up to 400 ~g/kg, but decreased at higher dose (up to 1000 ~g/kg) which produced the convulsions characteristic of.this toxin. In no caso did the frequency of thrombi (expressed as the percentage of vessels occuded with thrombi) exceed 70%. Histological examination by light microscopy showed that there was no thrombus formation in other organs such as heart, kidney and tiver. Heparin and dermatan (anionic molecules) were partially effective at preventing the thrmbotic action of convulxin, particularlyat low doses ofthe latter, perhaps through a direct electrostatic interaction with convulxin. Mepyramine (histaminer H2 , receptorantagonist), methysergide (5-HT receptor antagonist) and metronidazole há no effect on the formation of thrombi induced by convulxin. Sirnilary, prostacyclin, which increases intracelular cAMP levels, dazoxiben, a thromboxane A2 synthase inhibitor, and aspirin, a cyc100xygenase inhibitor, did not inhibit convulxin-induced thrombosis. These results suggest that is no direct reationship between the platelet aggregation and the convulsions produced by convulxin and that mediators known to affect convulxin-induce aggregation do not affect the thrombotic activity, perhaps because these actions involve different pathways.

ASSUNTO(S)

heparina agregação plaquetaria

ACESSO AO ARTIGO

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