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Title: Toxins not neutralized by brown snake antivenom

Abstract

The Australian snakes of the genus Pseudonaja (dugite, gwardar and common brown) account for the majority of snake bite related deaths in Australia. Without antivenom treatment, the risk of mortality is significant. There is an accumulating body of evidence to suggest that the efficacy of the antivenom is limited. The current study investigates the protein constituents recognized by the antivenom using 2-DE, immuno-blot techniques and rat tracheal organ bath assays. The 2-DE profiles for all three snake venoms were similar, with major species visualized at 78-132 kDa, 32-45 kDa and 6-15 kDa. Proteins characterized by LC-MS/MS revealed a coagulant toxin ({approx}42 kDa) and coagulant peptide ({approx}6 kDa), as well as two PLA{sub 2} ({approx}14 kDa). Peptides isolated from {approx}78 kDa and 15-32 kDa protein components showed no similarity to known protein sequences. Protein recognition by the antivenom occurred predominantly for the higher molecular weight components with little recognition of 6-32 kDa MW species. The ability of antivenom to neutralize venom activity was also investigated using rat tracheal organ bath assays. The venoms of Pseudonaja affinis affinis and Pseudonaja nuchalis incited a sustained, significant contraction of the trachea. These contractions were attributed to PLA{sub 2} enzymatic activity as pre-treatment with themore » PLA{sub 2} inhibitor 4-BPB attenuated the venom-induced contractions. The venom of Pseudonaja textilis incited tracheal contractility through a non-PLA{sub 2} enzymatic activity. Neither activity was attenuated by the antivenom treatment. These results represent the first proteomic investigation of the venoms from the snakes of the genus Pseudonaja, revealing a possible limitation of the brown snake antivenom in binding to the low MW protein components.« less

Authors:
 [1];  [2];  [3];  [4];  [5]
  1. Molecular Genetics and Evolution Group, Research School of Biological Sciences, Australian National University, Canberra 2601, ACT (Australia)
  2. School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Western Australia (Australia)
  3. Venom Supplies, Tanunda 5352, South Australia (Australia)
  4. School of Primary, Aboriginal and Rural Health Care, QEII Medical Centre, Western Australia (Australia)
  5. Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, VIC Victoria (Australia). E-mail: Jackie.Wilce@med.monash.edu.au
Publication Date:
OSTI Identifier:
20850333
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 213; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.09.010; PII: S0041-008X(05)00565-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACID SEQUENCE; BROMIDES; MOLECULAR WEIGHT; MORTALITY; PEPTIDES; PHOSPHATES; RATS; SNAKES; TOXINS; TRACHEA; VENOMS

Citation Formats

Judge, Roopwant K., Henry, Peter J., Mirtschin, Peter, Jelinek, George, and Wilce, Jacqueline A. Toxins not neutralized by brown snake antivenom. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.09.010.
Judge, Roopwant K., Henry, Peter J., Mirtschin, Peter, Jelinek, George, & Wilce, Jacqueline A. Toxins not neutralized by brown snake antivenom. United States. doi:10.1016/j.taap.2005.09.010.
Judge, Roopwant K., Henry, Peter J., Mirtschin, Peter, Jelinek, George, and Wilce, Jacqueline A. Thu . "Toxins not neutralized by brown snake antivenom". United States. doi:10.1016/j.taap.2005.09.010.
@article{osti_20850333,
title = {Toxins not neutralized by brown snake antivenom},
author = {Judge, Roopwant K. and Henry, Peter J. and Mirtschin, Peter and Jelinek, George and Wilce, Jacqueline A.},
abstractNote = {The Australian snakes of the genus Pseudonaja (dugite, gwardar and common brown) account for the majority of snake bite related deaths in Australia. Without antivenom treatment, the risk of mortality is significant. There is an accumulating body of evidence to suggest that the efficacy of the antivenom is limited. The current study investigates the protein constituents recognized by the antivenom using 2-DE, immuno-blot techniques and rat tracheal organ bath assays. The 2-DE profiles for all three snake venoms were similar, with major species visualized at 78-132 kDa, 32-45 kDa and 6-15 kDa. Proteins characterized by LC-MS/MS revealed a coagulant toxin ({approx}42 kDa) and coagulant peptide ({approx}6 kDa), as well as two PLA{sub 2} ({approx}14 kDa). Peptides isolated from {approx}78 kDa and 15-32 kDa protein components showed no similarity to known protein sequences. Protein recognition by the antivenom occurred predominantly for the higher molecular weight components with little recognition of 6-32 kDa MW species. The ability of antivenom to neutralize venom activity was also investigated using rat tracheal organ bath assays. The venoms of Pseudonaja affinis affinis and Pseudonaja nuchalis incited a sustained, significant contraction of the trachea. These contractions were attributed to PLA{sub 2} enzymatic activity as pre-treatment with the PLA{sub 2} inhibitor 4-BPB attenuated the venom-induced contractions. The venom of Pseudonaja textilis incited tracheal contractility through a non-PLA{sub 2} enzymatic activity. Neither activity was attenuated by the antivenom treatment. These results represent the first proteomic investigation of the venoms from the snakes of the genus Pseudonaja, revealing a possible limitation of the brown snake antivenom in binding to the low MW protein components.},
doi = {10.1016/j.taap.2005.09.010},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 213,
place = {United States},
year = {2006},
month = {6}
}