Isolation and characterisation of P-EPTX-Ap1a and P-EPTX-Ar1a: Pre-synaptic neurotoxins from the venom of the northern (Acanthophis praelongus) and Irian Jayan (Acanthophis rugosus) death adders

Chaisakul, Janeyuth; Konstantakopoulos, Nicki; Smith, A. Ian; Hodgson, Wayne Clarence

doi:10.1016/j.bcp.2010.05.008

Cited by 18 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until recently, post-synaptic neurotoxins were thought to be the most important components of death adder venom and numerous post-synaptic toxins have been isolated [2]–[6]. However, recent work has identified a number of pre-synaptic neurotoxins present in at least three species of death adder [7]–[9]. Several other components have been identified in death adder venom, including myotoxins, pro-coagulants, anticoagulants and toxins which interfere with platelet aggregation [10]–[17].…”

Section: Introductionmentioning

confidence: 99%

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Johnston

O’Leary²,

Brown³

et al. 2012

PLoS Negl Trop Dis

View full text Add to dashboard Cite

BackgroundDeath adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment.Methodology/Principal FindingsDefinite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5–74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5–15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5–168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4–245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom.Conclusions/SignificanceDeath adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

show abstract

Section: Introductionmentioning

confidence: 99%

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Johnston

O’Leary²,

Brown³

et al. 2012

PLoS Negl Trop Dis

View full text Add to dashboard Cite

show abstract

“…The identity and the purity of the isolated toxins were further verified using matrix-assisted laser desorption/ionization (MALDI-TOF) mass spectrometry(4700 Proteomics Analyser MALDI TOF/TOF, AB Sciex, Foster City, CA, USA) as described previously [40,41]. HPLC and MALDI-TOF chromatograms are included as Supplementary Figure S1.…”

Section: Methodsmentioning

confidence: 99%

Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms

Silva

Hodgson

2016

Toxins

View full text Add to dashboard Cite

There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV). The chick biventer cervicis nerve-muscle preparation was used for this study. Antivenom was added to the organ bath 20 min prior to venom. Pre- and post-synaptic neurotoxicity of Bungarus caeruleus and Bungarus fasciatus venoms was neutralised by all antivenoms except TCAV, which did not neutralise pre-synaptic activity. Post-synaptic neurotoxicity of Ophiophagus hannah was neutralised by all antivenoms, and Naja kaouthia by all antivenoms except IPAV. Pre- and post-synaptic neurotoxicity of Notechis scutatus was neutralised by all antivenoms, except TCAV, which only partially neutralised pre-synaptic activity. Pre- and post-synaptic neurotoxicity of Oxyuranus scutellatus was neutralised by TNPAV and APAV, but TCAV and IPAV only neutralised post-synaptic neurotoxicity. Post-synaptic neurotoxicity of Acanthophis antarcticus was neutralised by all antivenoms except IPAV. Pseudonaja textillis post-synaptic neurotoxicity was only neutralised by APAV. The α-neurotoxins were neutralised by TNPAV and APAV, and taipoxin by all antivenoms except IPAV. Antivenoms raised against venoms with post-synaptic neurotoxic activity (TCAV) cross-neutralised the post-synaptic activity of multiple snake venoms. Antivenoms raised against pre- and post-synaptic neurotoxic venoms (TNPAV, IPAV, APAV) cross-neutralised both activities of Asian and Australian venoms. While acknowledging the limitations of adding antivenom prior to venom in an in vitro preparation, cross-neutralization of neurotoxicity means that antivenoms from one region may be effective in other regions which do not have effective antivenoms. TCAV only neutralized post-synaptic neurotoxicity and is potentially useful in distinguishing pre-synaptic and post-synaptic effects in the chick biventer cervicis preparation.

show abstract

“…All 12 patients an elevated white cell count, with a median peak value of 17.5610 9 (Range 11.4-41.9610 9 ) and an elevated neutrophil count, with a median value of 15.5610 9 (range 10.4-39. 3610 9 ).…”

Section: Laboratory Investigationsmentioning

confidence: 98%

“…Until recently, post-synaptic neurotoxins were thought to be the most important components of death adder venom and numerous post-synaptic toxins have been isolated [2][3][4][5][6]. However, recent work has identified a number of pre-synaptic neurotoxins present in at least three species of death adder [7][8][9]. Several other components have been identified in death adder venom, including myotoxins, pro-coagulants, anticoagulants and toxins which interfere with platelet aggregation [10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

232. Death Adder Envenoming Causes Neurotoxicity not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Johnston

O’Leary

Brown

et al. 2012

Toxicon

View full text Add to dashboard Cite

show abstract

Isolation and characterisation of P-EPTX-Ap1a and P-EPTX-Ar1a: Pre-synaptic neurotoxins from the venom of the northern (Acanthophis praelongus) and Irian Jayan (Acanthophis rugosus) death adders

Cited by 18 publications

References 31 publications

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms

232. Death Adder Envenoming Causes Neurotoxicity not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Contact Info

Product

Resources

About