SURAMIN AND POLYETHYLENE GLYCOL ANTAGONIZE THE MYOTOXIC EFFECT OF Agkistrodon contortrix laticinctus CRUDE VENOM AND ITS MYOTOXIN

SERAFIM A.D. (1), TOMAZ M. A. (1), WILLIAMS, K. (3), MURAKAMI, M.T. (2), ARNI, R.K. (2), OWNBY, C.L. (4), MELO, P.A. (1)

(1) Departamento de Farmacologia Básica e Clínica ICB, CCS, Universidade Federal do Rio de Janeiro, 21941-590, Rio de, Janeiro, RJ, Brazil, (2) Departament of Physics IBILCE/UNESP, São José do Rio Preto, SP, Brazil

(4) Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA

We assessed the effects of suramin and polyethylene glycol (PEG400) against the myotoxicity of Agkistrodon contortrix laticinctus (ACL) crude venom and its myotoxin on mouse isolated extensor digitorum longus (EDL) and neuromuscular diaphragm preparation. Isolated EDL were exposed to ACL crude venom and myotoxin (25 µg/mL) alone or together with suramin (10 and 30 µM) and PEG (10 and 30 mM). The rate of creatine kinase (CK) release from the muscles was measured, indicating tissue damage. Basal CK release from EDL was 0,43±0,06 U.g-1.h-1, and after 60 minutes of exposure to the myotoxin and treatments it  increased to 13,76±3,76 (ACL myotoxin), 5,90±1,19 and 2,10±0,86 (myotoxin plus suramin 10 and 30 µM, respectively), and 8,87±3,63 and 5,80±2,04 (myotoxin plus PEG 10 and 30 mM, respectively). ACL crude venom (60 min) also induced an increase in the rate of CK release up to 32,07±5,43 U.g-1.h-1, which was significantly inhibited by PEG 100 mM (6,47±3,14 U.g-1.h-1). Mouse neuromuscular diaphragm preparation was exposed to ACL crude venom and venom plus suramin. The preparation was directly (muscle) and indirectly (nerve) stimulated, and twitch amplitude was recorded. The snake venom (12,5 and 25 µg/mL) decreased twitch amplitude down to 25% of the control in approximately 30 to 40 min in both protocols. Suramin  prevented in a concentration-dependent fashion the venom’s effect (20, 25 and 50 mM caused a 5, 40 and 100% inhibition on the depressing effect of ACL crude venom, respectively). Data show that suramin and PEG are able to prevent the myotoxic activities of ACL crude venom and its myotoxin in mouse isolated muscle and suramin prevents the neuromuscular effects of ACL crude venom.

SUPPORTED BY CNPq, CAPES, FAPERJ,  PRONEX, FAPESP

KEY WORDS Cooperhead venom; Myotoxicity; Suramin and polyethylene glycol

CORRESPONDENCE:pamelo@farmaco.ufrj.br