Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators

doi:10.1016/j.toxicon.2006.11.020

Toxicon

Volume 49, Issue 5, April 2007, Pages 734-739

https://doi.org/10.1016/j.toxicon.2006.11.020 Get rights and content

Abstract

Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented.

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Acknowledgements

We would like to acknowledge the Gunter Charitable Trust, UK for financial support (J.-M.H). We would also like to thank the Nigerian Ministry of Health for the collection of E. ocellatus and P.D. Rowley for help with the extraction of the venom. We thank Dr. Simon Wagstaff of the Alistair Reid Venom Research Unit for critical reading of this manuscript.

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Short communicationNeutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators

Abstract

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Acknowledgements

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Crit. Rev. Oncol. Hematol.

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Gene

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Short communication
Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators