INHIBITION OF MYOTOXIC AND PHOSPHOLIPASE ACTIVITIES OF CROTOXIN BY SURAMIN

Arruda, E.Z.; Fernandes, F.F.A.; Moraes, R.A.M.; Pinheiro, D.A.; Melo, P.A.

Departamento de Farmacologia Básica e Clínica, ICB, UFRJ, Rio de Janeiro, RJ, Brazil.

Suramin is an enzymatic inhibitor and an uncoupler of G-protein from receptors. We investigated the protective effect of suramin on myotoxic activity of crotoxin (CTX) in mice. The myotoxicity was evaluated in vivo by intramuscular injections (i.m.) of CTX (0.5mg/kg) prepared in physiological saline solution (PSS, 0.1ml). The potential protective effects of suramin were evaluated using two different experimental approaches. In protocol A, CTX was pre-incubated with 1.0mg suramin (15 min, 37C, in vitro), and then injected i.m. into mice at a dose of 0.5mg/kg (in vivo). In protocol B, CTX was i.m. injected 15 min prior to suramin(1.0mg/kg, i.v.). Before and 2h after the i.m. injections, the animals were lightly anesthetized with diethyl ether and the blood was collected by orbital puncture. The plasma was separated by centrifugation and stored at 4C for subsequent determination of creatinekinase (CK) activity. Intramuscular injection of CTX increased the CK plasma activity from the control level 71.1 ± 7.4 U/L (n=25) to 943.33 ± 95.93 u/L (n=5). In both protocols, A and B, suramin reduced the increase of CK plasma activity 70% and 60%, respectively. In the study of phospholipase activity by the turbidimetric method (Marinetti et. al., 98:554, 1964), the CTX concentration response curve was determined (1-100mcg/ml) and pre-incubation of suramin reduced phospholipase activity by almost 30%. These data indicate that suramin reduced CTX phospholipase activity in vitro and also its myotoxicity in vivo.

Financial support: CAPES, FAPERJ, CNPq, PRONEX, FUJB-UFRJ.

CORRESPONDENCE TO:

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