Effectiveness of batimastat, a synthetic inhibitor of matrix metalloproteinases, in neutralizing local tissue damage induced by BaP1, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper
Escalante Muñoz, Teresa
Rucavado Romero, Alexandra
Gutiérrez, José María
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Batimastat (BB-94), a synthetic hydroxamate peptidomimetic matrix metalloproteinase inhibitor, was tested for its ability to inhibit proteolytic and toxic effects induced by BaP1, a 24-kDa hemorrhagic metalloproteinase isolated from the venom of Bothrops asper, the medically most important snake species in Central America and southern Mexico. Batimastat inhibited proteolytic activity on biotinylated casein, with anic50 of 80 nM. In addition, batimastat was effective in inhibiting hemorrhagic, dermonecrotic, and edema-forming activities of this metalloproteinase if incubated with the enzyme prior to the assays. When the inhibitor was administered i.m. at the site of the toxin injection without preincubation, rapidly after metalloproteinase administration, it totally abrogated the hemorrhagic and dermonecrotic effects of BaP1. Inhibition was less effective as the time lapse between toxin and batimastat injection increased, due to the extremely rapid development of BaP1-induced local tissue damage in this experimental model. On the other hand, batimastat was ineffective if administered by the i.p. route immediately after toxin injection. It is concluded that batimastat, and probably other synthetic metalloproteinase inhibitors, may become useful therapeutic tools aimed at the in situ inhibition of venom metalloproteinases, when injected at the site of the bite rapidly after envenomation.
External link to the item10.1016/S0006-2952(00)00302-6
- Microbiología 
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Effect of the metalloproteinase inhibitor batimastat in the systemic toxicity induced by Bothrops asper snake venom: understanding the role of metalloproteinases in envenomation Rucavado Romero, Alexandra; Escalante Muñoz, Teresa; Gutiérrez, José María (2014-03-15)The peptidomimetic hydroxamate metalloproteinase inhibitor batimastat (BB-94) was assessed for its ability to neutralize the systemic effects (lethality, hemorrhage and coagulopathy) induced by the venom of Bothrops asper, ...
Isolation and characterization of a metalloproteinase with weak hemorrhagic activity from the venom of the snake Bothrops asper (terciopelo) Gutiérrez, José María; Romero, Marjorie; Díaz Oreiro, Cecilia; Borkow, Gadi; Ovadia, Michael (1995-01)A metalloproteinase, named BaP1, was purified to homogeneity from the venom of Bothrops asper (Pacific region) of Costa Rica by ion-exchange chromatography on CM-Sephadex and gel filtration on Sephacryl S-200. The enzyme ...
Local tissue damage induced by BaP1, a metalloproteinase isolated from Bothrops asper (Terciopelo) snake venom Rucavado Romero, Alexandra; Lomonte, Bruno; Ovadia, Michael; Gutiérrez, José María (1995-12)The pathogenesis of hemorrhage and other local effects induced by the metalloproteinase BaP1, isolated from Bothrops asper venom, was investigated using various in vivo and in vitro models. Upon intramuscular injection in ...