The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro

Despite antivenoms being the only established specific treatment for neuromuscular paralysis arising from snake envenoming, their ability to reverse the post-synaptic neurotoxicity in snake envenoming is poorly understood. We investigated the ability of five commercial antivenoms i.e., King cobra mo...

Full description

Bibliographic Details
Main Authors: Tam M. Huynh, Wayne C. Hodgson, Geoffrey K. Isbister, Anjana Silva
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/14/4/277
_version_ 1797409140809662464
author Tam M. Huynh
Wayne C. Hodgson
Geoffrey K. Isbister
Anjana Silva
author_facet Tam M. Huynh
Wayne C. Hodgson
Geoffrey K. Isbister
Anjana Silva
author_sort Tam M. Huynh
collection DOAJ
description Despite antivenoms being the only established specific treatment for neuromuscular paralysis arising from snake envenoming, their ability to reverse the post-synaptic neurotoxicity in snake envenoming is poorly understood. We investigated the ability of five commercial antivenoms i.e., King cobra monovalent, Thai cobra monovalent, Thai neuro polyvalent, Indian polyvalent and Australian polyvalent antivenoms to reverse neurotoxicity induced by the venoms of King cobra (<i>Ophiophagus hannah</i>, 3 µg/mL), Indian cobra <i>(Naja naja</i>, 5 µg/mL) and Thai cobra (<i>Naja kaouthia</i>, 3 µg/mL) using the in vitro chick-biventer cervicis nerve–muscle preparation. All three venoms displayed post-synaptic neurotoxicity, which was prevented by all tested antivenoms (40 µL/mL) added to the bath prior to venom. All antivenoms partially reversed the established post-synaptic neuromuscular block after the addition of the three venoms during a 180 min observation period, but to varying degrees and at different rates. The neurotoxic effects of <i>O. hannah</i> venom recovered to a greater magnitude (based on twitch height restoration) and faster than the neurotoxicity of <i>N. kaouthia</i> venom, which recovered to a lower magnitude more slowly. The recovery of post-synaptic neurotoxicity by <i>N. naja</i> venom was hindered due to the likely presence of cytotoxins in the venom, which cause direct muscle damage. The observations made in this study provide further evidence that the commercial antivenoms are likely to actively reverse established α-neurotoxin-mediated neuromuscular paralysis in snake envenoming, and there is cross-neutralisation with different antivenoms.
first_indexed 2024-03-09T04:10:01Z
format Article
id doaj.art-cd439b72236b40f795af12abb85a050e
institution Directory Open Access Journal
issn 2072-6651
language English
last_indexed 2024-03-09T04:10:01Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series Toxins
spelling doaj.art-cd439b72236b40f795af12abb85a050e2023-12-03T14:01:59ZengMDPI AGToxins2072-66512022-04-0114427710.3390/toxins14040277The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In VitroTam M. Huynh0Wayne C. Hodgson1Geoffrey K. Isbister2Anjana Silva3Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaDespite antivenoms being the only established specific treatment for neuromuscular paralysis arising from snake envenoming, their ability to reverse the post-synaptic neurotoxicity in snake envenoming is poorly understood. We investigated the ability of five commercial antivenoms i.e., King cobra monovalent, Thai cobra monovalent, Thai neuro polyvalent, Indian polyvalent and Australian polyvalent antivenoms to reverse neurotoxicity induced by the venoms of King cobra (<i>Ophiophagus hannah</i>, 3 µg/mL), Indian cobra <i>(Naja naja</i>, 5 µg/mL) and Thai cobra (<i>Naja kaouthia</i>, 3 µg/mL) using the in vitro chick-biventer cervicis nerve–muscle preparation. All three venoms displayed post-synaptic neurotoxicity, which was prevented by all tested antivenoms (40 µL/mL) added to the bath prior to venom. All antivenoms partially reversed the established post-synaptic neuromuscular block after the addition of the three venoms during a 180 min observation period, but to varying degrees and at different rates. The neurotoxic effects of <i>O. hannah</i> venom recovered to a greater magnitude (based on twitch height restoration) and faster than the neurotoxicity of <i>N. kaouthia</i> venom, which recovered to a lower magnitude more slowly. The recovery of post-synaptic neurotoxicity by <i>N. naja</i> venom was hindered due to the likely presence of cytotoxins in the venom, which cause direct muscle damage. The observations made in this study provide further evidence that the commercial antivenoms are likely to actively reverse established α-neurotoxin-mediated neuromuscular paralysis in snake envenoming, and there is cross-neutralisation with different antivenoms.https://www.mdpi.com/2072-6651/14/4/277neurotoxinpostsynapticsnakeantivenomneuromuscularskeletal muscle
spellingShingle Tam M. Huynh
Wayne C. Hodgson
Geoffrey K. Isbister
Anjana Silva
The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
Toxins
neurotoxin
postsynaptic
snake
antivenom
neuromuscular
skeletal muscle
title The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
title_full The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
title_fullStr The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
title_full_unstemmed The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
title_short The Effect of Australian and Asian Commercial Antivenoms in Reversing the Post-Synaptic Neurotoxicity of <i>O. hannah</i>, <i>N. naja</i> and <i>N. kaouthia</i> Venoms In Vitro
title_sort effect of australian and asian commercial antivenoms in reversing the post synaptic neurotoxicity of i o hannah i i n naja i and i n kaouthia i venoms in vitro
topic neurotoxin
postsynaptic
snake
antivenom
neuromuscular
skeletal muscle
url https://www.mdpi.com/2072-6651/14/4/277
work_keys_str_mv AT tammhuynh theeffectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT waynechodgson theeffectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT geoffreykisbister theeffectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT anjanasilva theeffectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT tammhuynh effectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT waynechodgson effectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT geoffreykisbister effectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro
AT anjanasilva effectofaustralianandasiancommercialantivenomsinreversingthepostsynapticneurotoxicityofiohannahiinnajaiandinkaouthiaivenomsinvitro