Neurotoxic effects of venoms from seven species of australasian black snakes (<i>Pseudechis</i>): Efficacy of black and tiger snake antivenoms

Ramasamy, Sharmaine; Fry, Bryan G.; Hodgson, Wayne Clarence

doi:10.1111/j.1440-1681.2005.04151.x

Cited by 24 publications

(13 citation statements)

References 23 publications

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“…4D). The strong reactivity of the antivenom in the low molecular size region corresponding to neurotoxins is consistent with the reported ability of this antivenom to neutralize neurotoxin activity (45).…”

Section: Diversity In Australian Snake Venomssupporting

confidence: 71%

The Diversity of Bioactive Proteins in Australian Snake Venoms

Birrell

Earl

Wallis

et al. 2007

Molecular & Cellular Proteomics

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Australian elapid snakes are among the most venomous in the world. Their venoms contain multiple components that target blood hemostasis, neuromuscular signaling, and the cardiovascular system. We describe here a comprehensive approach to separation and identification of the venom proteins from 18 of these snake species, representing nine genera. The venom protein components were separated by two-dimensional PAGE and identified using mass spectrometry and de novo peptide sequencing. The venoms are complex mixtures showing up to 200 protein spots varying in size from <7 to over 150 kDa and in pI from 3 to >10. These include many proteins identified previously in Australian snake venoms, homologs identified in other snake species, and some novel proteins. In many cases multiple trains of spots were typically observed in the higher molecular mass range (>20 kDa) (indicative of posttranslational modification). Venom proteins and their posttranslational modifications were characterized using specific antibodies, phosphoprotein-and glycoprotein-specific stains, enzymatic digestion, lectin binding, and antivenom reactivity. In the lower molecular weight range, several proteins were identified, but the predominant species were phospholipase A 2 and ␣-neurotoxins, both represented by different sequence variants. The higher molecular weight range contained proteases, nucleotidases, oxidases, and homologs of mammalian coagulation factors. This information together with the identification of several novel proteins (metalloproteinases, vespryns, phospholipase A 2 inhibitors, protein-disulfide isomerase, 5-nucleotidases, cysteinerich secreted proteins, C-type lectins, and acetylcholinesterases) aids in understanding the lethal mechanisms of elapid snake venoms and represents a valuable resource for future development of novel human therapeutics.

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Section: Diversity In Australian Snake Venomssupporting

confidence: 71%

The Diversity of Bioactive Proteins in Australian Snake Venoms

Birrell

Earl

Wallis

et al. 2007

Molecular & Cellular Proteomics

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“…Various methods have been implemented to evaluate the inhibitory effect of snake venoms on neuromuscular preparations ex vivo [74,75,76,77]. The time to reach either 50% or 90% neuromuscular blockade is estimated.…”

Section: The Complex Pathophysiology Of Snakebite Envenoming Demanmentioning

confidence: 99%

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

127

100

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Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics.

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“…However, the report only included photographs and little further information. Animal studies have demonstrated that spotted black snake venom is both neurotoxic and myotoxic, 8 , 9 and both effects are neutralised by black and tiger snake antivenoms. However, neither of our patients had any evidence of significant neurotoxicity or myotoxicity that may be expected from in‐vitro studies.…”

Section: Discussionmentioning

confidence: 99%