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

Anjana Silva,Wayne Hodgson,Geoffrey Isbister

doi:10.3390/toxins8100302

Anjana Silva, Wayne Hodgson + Show 1 more

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https://doi.org/10.3390/toxins8100302

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Abstract

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.

Highlights

Snakebites impose a considerable health and socioeconomic burden on many nations in southern and south-eastern Asian
Antivenoms raised against pre- and post-synaptic neurotoxic venoms (TNPAV, Indian polyvalent antivenom (IPAV), Australian polyvalent antivenom (APAV)) cross-neutralised both activities of Asian and Australian venoms
Prevent theinhibition inhibitionofofindirect indirecttwitches twitches but but prevented prevented the the abolition abolition of of the the response response of of the the chick chick biventer biventer preparation preparation to to exogenous exogenous nicotinic nicotinic agonists, agonists, indicating the neutralisation of post-synaptic effects, but not the pre-synaptic neurotoxicity indicating the neutralisation of post‐synaptic effects, but not the pre‐synaptic neurotoxicity of of the the venom

Summary

Introduction

Snakebites impose a considerable health and socioeconomic burden on many nations in southern and south-eastern Asian This is due to the large number of cases of envenomings that cause acute, life-threatening, and debilitating long-term consequences [1,2,3,4]. Toxins 2016, 8, 302 respiratory muscle paralysis that requires early and often prolonged intervention with intubation and mechanical ventilation [5] Envenoming by snakes such as kraits (genus Bungarus), some species of cobras (genera Naja and Ophiophagus), taipans (genus Oxyuranus), death adders (genus Acanthophis), tiger snakes (genus Notechis) and coral snakes (genus Micrurus) commonly leads to life threatening neuromuscular paralysis [5]. Snake venom pre-synaptic neurotoxins (i.e., β-neurotoxins) are usually phospholipase A2 (PLA2 ) toxins They enter the motor nerve terminal and lead to a depletion of synaptic vesicles by facilitating exocytosis and inhibiting synaptic vesicle recycling. This is followed by the rapid degeneration of the motor nerve terminal which is not reversible with treatment [7,8]

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