In vivo diminution by chelators of snake venom-provoked hemorrhage and in vitro inhibition of proteolytic activity

Topical application of alcohol-soluble metal-complexing agents, particularly α-mercapto-β-(2-furyl)acrylic acid (MFA)1, diminished the severity of hemorrhages caused by s.c. injection to mice of thirteen hemorrhagic pit viper venoms and two viper venoms. Metal dependency of the alkaline protease activity ranged from 0 to 100% for these venoms, plus one non-hemorrhagic pit viper venom; MFA completely inhibited this activity in six pit viper and two viper venoms. The presence of zinc-dependent proteases in venoms of Crotalus atrox and Bitis arietans was indicated. Less compelling evidence suggested the presence of zinc metalloproteases in at least 11 of 14 other venoms. The potencies of hemorrhagic and alkaline protease activities were not related in the venoms and we did not investigate if metalloproteases were the targets of chelator antagonism of hemorrhage development. Topically active chelators may be useful as adjunctive therapy in some snake envenomations.