Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Clinical Toxicology Research Group, University of Newcastle, Newcastle, NSW 2298, Australia.
Toxins (Basel). 2022 Apr 13;14(4):277. doi: 10.3390/toxins14040277.
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 (, 3 µg/mL), Indian cobra , 5 µg/mL) and Thai cobra (, 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 venom recovered to a greater magnitude (based on twitch height restoration) and faster than the neurotoxicity of venom, which recovered to a lower magnitude more slowly. The recovery of post-synaptic neurotoxicity by 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.
尽管抗蛇毒血清是治疗蛇毒引起的神经肌肉麻痹的唯一特效治疗方法，但人们对其逆转蛇毒中毒后突触后神经毒性的能力知之甚少。我们用鸡二腹肌-颈神经标本研究了 5 种市售抗蛇毒血清，即眼镜王蛇单价、泰国眼镜蛇单价、泰国神经多价、印度多价和澳洲多价抗蛇毒血清，对眼镜王蛇毒液（3 µg/mL）、印度眼镜蛇毒液（5 µg/mL）和泰国眼镜蛇毒液（3 µg/mL）诱导的神经毒性的逆转能力。三种毒液均显示出突触后神经毒性，在用毒液前加入浴液中的所有测试抗蛇毒血清（40 µL/mL）均可预防。所有抗蛇毒血清均能部分逆转在 180 分钟观察期内加入三种毒液后建立的突触后神经肌肉阻滞，但程度和速度不同。毒液的神经毒性效应恢复到更大的程度（基于抽搐高度恢复），比毒液更快，毒液的神经毒性恢复到更低的程度更慢。毒液的突触后神经毒性恢复受到阻碍，可能是由于毒液中存在细胞毒素，直接损伤肌肉。本研究的观察结果进一步证明，商业抗蛇毒血清可能积极逆转蛇毒中毒后已建立的α-神经毒素介导的神经肌肉麻痹，并且不同抗蛇毒血清之间存在交叉中和作用。
