Ability of wedelolactone, heparin, and para-bromophenacyl bromide to antagonize the myotoxic effects of two crotaline venoms and their PLA(2) myotoxins

We examined the ability of wedelolactone, heparin and para-bromophenacyl br omide to antagonize the myotoxic activity in mice of Venoms from Crotalus v iridis viridis and Agkistrodon contortrix laticinctus and two phospholipase Al? myotoxins, CW myotoxin and ACL myotoxin, isolated from them. Myotoxici ty was measured by the increase in plasma creatine kinase (CK) activity at two hours and histological changes in extensor digitorum longus muscle (EDL ) at three hours after injection of the test solution. Both heparin and wed elolactone independently reduced the myotoxic effect of both crude venoms a nd both myotoxins, but wedelolactone was more effective. Wedelolactone plus heparin reduced the myotoxic effect of CW myotoxin more than either antago nist alone. The PLA(2) inhibitor, para-bromophenacyl bromide (pBPB), reduce d the myotoxic effect of both myotoxins more than either wedelolactone or h eparin. On the other hand, the myotoxic effect of polylysine was not reduce d by either wedelolactone or para-bromophenacyl bromide, but it was reduced by heparin. These results indicate that wedelolactone, para-bromophenacyl bromide and heparin are antagonists of these two phospholipase A(2) myotoxi ns, and that antagonism by the first two compounds may be due to a more spe cific interaction with these proteins than that by the latter. (C) 1998 Els evier Science Ltd. All rights reserved.