Inhibition of local hemorrhage and dermonecrosis induced by Bothrops aspersnake venom: Effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa(2)EDTA

The effectiveness of the chelating agent CaNa(2)EDTA and the peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tis sue damage induced by Bothrops asper snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic eff ects, and partially reduced edema-forming activity, when incubated with ven om prior to injection. Much lower concentrations of batimastat than of CaNa (2)EDTA were required to inhibit these effects. In addition, batimastat, bu t not CaNa(2)EDTA, partially reduced myotoxic activity of the venom. When t he inhibitors were administered at various time intervals after envenomatio n at the same site of venom injection, both compounds were effective in neu tralizing 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 metalloproteinase s in the pathogenesis of local tissue damage induced by B. asper and other pit viper venoms, it is suggested that administration of peptidomimetic met alloproteinase inhibitors or CaNa(2)EDTA at the site of venom injection may represent a useful alternative to complement antivenoms in the neutralizat ion of venom-induced local tissue damage.