The ability of two
peptidomimetic hydroxamate
metalloproteinase inhibitors,
Batimastat and
Marimastat, to abrogate toxic and
proteinase activities of the
venom of Echis ocellatus from Cameroon and Ghana was assessed. Since this
venom largely relies for its toxicity on the action of
zinc-dependent
metalloproteinases (SVMPs), the hypothesis was raised that toxicity could be largely eliminated by using SVMP inhibitors. Both hydroxamate molecules inhibited local and pulmonary hemorrhagic, in vitro
coagulant, defibrinogenating, and
proteinase activities of the
venoms in conditions in which
venom and inhibitors were incubated prior to the test. In addition, the inhibitors prolonged the time of death of mice receiving 4 LD50s of
venom by the intravenous route. Lower values of IC50 were observed for in vitro and local hemorrhagic activities than for systemic effects. When experiments were performed in conditions that simulated the actual circumstances of
snakebite, i.e. by administering the inhibitor after envenoming,
Batimastat completely abrogated local
hemorrhage if injected immediately after
venom. Moreover, it was also effective at inhibiting lethality and defibrinogenation when
venom and inhibitor were injected by the intraperitoneal route. Results suggest that these, and possibly other,
metalloproteinase inhibitors may become an effective adjunct
therapy in envenomings by E. ocellatus when administered at the anatomic site of
venom injection rapidly after the
bite.