The effectiveness of the
chelating agent CaNa2EDTA and the
peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tissue damage induced by Bothrops asper
snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic effects, and partially reduced
edema-forming activity, when incubated with
venom prior to injection. Much lower concentrations of
batimastat than of CaNa2EDTA were required to inhibit these effects. In addition,
batimastat, but not CaNa2EDTA, partially reduced myotoxic activity of the
venom. When the inhibitors were administered at various time intervals after envenomation at the same site of
venom injection, both compounds were effective in neutralizing local
hemorrhage and dermonecrosis if administered rapidly after
venom. Inhibition was not as effective as the time lapse between
venom and inhibitor
injections increased. Owing to the relevance of
metalloproteinases in the pathogenesis of local tissue damage induced by B. asper and other
pit viper venoms, it is suggested that administration of
peptidomimetic metalloproteinase inhibitors or CaNa2EDTA at the site of
venom injection may represent a useful alternative to
complement antivenoms in the neutralization of
venom-induced local tissue damage.