Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom:: Effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA
Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom:: Effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA
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DOI：
10.4269/ajtmh.2000.63.313
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发表时间：
2000-11-01
影响因子：
3.3
通讯作者：
Gutiérrez, JM
中科院分区：
文献类型：
--
作者：
Rucavado, A;Escalante, T;Gutiérrez, JM
在小鼠身上研究了螯合剂 CaNa(2)EDTA 和拟肽基质金属蛋白酶抑制剂巴马司他 (BB-94) 抑制白蛇蛇毒引起的局部组织损伤的有效性。当注射前与毒液一起孵育时，这两种化合物完全抑制蛋白水解、出血和皮肤坏死作用，并部分降低水肿形成活性。抑制这些作用所需的巴马司他浓度比 CaNa(2)EDTA 浓度低得多。此外，巴马司他（而非CaNa(2)EDTA）部分降低了毒液的肌肉毒性活性。当毒液注射后在不同时间间隔在同一毒液注射部位施用抑制剂时，如果在毒液注射后迅速施用，两种化合物均能有效中和局部出血和皮肤坏死。随着毒液和抑制剂注射之间的时间间隔增加，抑制效果不那么有效。由于金属蛋白酶在 B. asper 和其他响尾蛇毒液引起的局部组织损伤发病机制中的相关性，建议在毒液注射部位施用拟肽金属蛋白酶抑制剂或 CaNa(2)EDTA 可能是补充抗蛇毒血清中和毒液引起的局部组织损伤的有用替代方案。
The effectiveness of the chelating agent CaNa(2)EDTA 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 CaNa(2)EDTA were required to inhibit these effects. In addition, batimastat, but not CaNa(2)EDTA, 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 CaNa(2)EDTA at the site of venom injection may represent a useful alternative to complement antivenoms in the neutralization of venom-induced local tissue damage.