Neutralization of a snake venom hemorrhagic metalloproteinase prevents coagulopathy after subcutaneous injection of Bothrops jararaca venom in rats.
Journal - Toxicon : official journal of the International Society on Toxinology (England )
Coagulopathy is one of the major complications following envenomations by crotalid and viperid snakes. The present study was undertaken to examine the effect of a hemorrhagic metalloproteinase in Bothrops jararaca venom, jararafibrase I (JF I), on the development of coagulopathy using rat snakebite model. Coagulation parameters were monitored after subcutaneous injection of B. jararaca crude venom, JF I-neutralized venom and purified JF I in rats. Crude venom induced unclottable blood and fibrinogen consumption, while JF I-neutralized venom and purified JF I did not induce coagulopathy. Plasma venom antigen level of rats given JF I-neutralized venom was lower than that of rats given crude venom. We conclude that venom hemorrhagic metalloproteinases play an important role in the development of coagulopathy through rapid spreading of venom coagulation components from the injected area into systemic circulation.
|ISSN : ||0041-0101|
|Mesh Heading : ||Animals Antivenins Blood Coagulation Blotting, Western Crotalid Venoms Disease Models, Animal Electrophoresis, Polyacrylamide Gel Hemorrhage Immunoglobulin G Male Metalloendopeptidases Prothrombin Time Rabbits Rats Rats, Wistar pharmacology drug effects enzymology immunology therapy therapeutic use immunology|
|Mesh Heading Relevant : ||Bothrops Fibrinolytic Agents therapeutic use antagonists & inhibitors prevention & control antagonists & inhibitors|
Inhibition of a snake venom hemorrhagic metalloproteinase by human and rat alpha-macroglobulins.
Journal - Toxicon : official journal of the International Society on Toxinology (ENGLAND )
Jararafibrase I is a hemorrhagic metalloproteinase purified from Bothrops jararaca venom, which induces local hemorrhage by degrading the basement membrane components. The present study was undertaken to investigate the inhibition of jararafibrase I by human and rat serum proteinase inhibitors. The proteolytic activity of jararafibrase I was completely inhibited by human and rat sera. In particular, rat serum displayed a greater inhibitory capacity. The inhibitory capacities of both sera were dependent on alpha-macroglobulins. SDS-PAGE analysis revealed that jararafibrase I formed complexes with alpha-macroglobulins that were present in normal sera. The proteolytic activity of jararafibrase I was completely inhibited by alpha1-macroglobulin and murinoglobulin in rat serum, and by human alpha2-macroglobulin. The inhibition molar ratios of alpha-macroglobulin/jararafibrase I were 1.5 for rat alpha1-macroglobulin and human alpha2-macroglobulin, and 2.4 for rat murinoglobulin. SDS-PAGE under reducing conditions demonstrated that the bait region of human alpha2-macroglobulin and rat murinoglobulin was cleaved by jararafibrase I. The bait region cleavage sites were identified as being situated at the 696Arg-697Leu peptide bond in human alpha2-macroglobulin, and at the 686Ala-687Val peptide bond in rat murinoglobulin.
|ISSN : ||0041-0101|
|Mesh Heading : ||Amino Acid Sequence Animals Antifibrinolytic Agents Enzyme Inhibitors Fibrinolytic Agents Hemorrhage Humans Hydrolysis Metalloendopeptidases Rats Scorpion Venoms Snake Venoms alpha-Macroglobulins pharmacology chemically induced chemistry chemistry|
|Mesh Heading Relevant : ||pharmacology antagonists & inhibitors toxicity enzymology pharmacology|