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

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.

Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom

“…In two animals, attempts were made to assess whether the neurotoxic effect was due to alpha-neurotoxins acting at the cholinergic receptor of the motor end-plate of muscle fibers; a combination of edrophonium (1 mg/kg) and atropine (0.02 mg/kg) combined in the same syringe was administered slowly intravenously over one minute in two animals receiving a lethal dose of the venom. No clinically observable improvement in strength occurred, suggesting, but not proving, the absence of any contribution by post-synaptically acting alpha-neurotoxins [ 35 , 36 ]. Notably, no animal in the study required any additional analgesia more than the mandatory two initial doses required by protocol (see Materials and Methods Detail, Section 5 ).…”

“…It may simply be that the high affinity of the alpha toxins towards the nAChR cannot be overcome by anticholinesterases. One straightforward method of showing this in other models is the isolated chick-biventer nerve-muscle preparation, which differentiates pre-synaptic from post-synaptic neurotoxicity [ 35 , 36 ]. However, this was not part of the present study, which was conducted on pigs.…”

A Review and Database of Snake Venom Proteomes

“…Demonstrating that there is a limited number of protein families in snake venoms, which is even more limited for major snake families or sub-families, supports efforts to develop universal anti-venoms [ 111 ].This explains the cross-neutralization of venoms by different anti-venoms, such as Asian and Australian anti-venoms cross-neutralizing neurotoxicity [ 112 ], and cross-neutralization of pit-viper venoms [ 113 ].…”

Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches

“…kauothia ) used in this study predominately cause flaccid paralysis and severe local necrosis in envenomed subjects. Other relevant in-vivo tests such as minimum necrotic dose [ 26 ] and in-vitro nerve-muscle preparations [ 27 , 28 ] should be performed before we can claim the clinical effectiveness of FNAV against N . siamensis and N .…”