Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Rd, Guangzhou 510120, China.
Toxins (Basel). 2021 Jan 11;13(1):49. doi: 10.3390/toxins13010049.
, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. venom contains pre-synaptic PLA neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of venom, and the efficacy of specific monovalent Chinese antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. venom (1-10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t time point after the addition of venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of antivenom (60 U/mL), at the t or t time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t values. Repeated washing of the preparation with physiological salt solution, commencing at the t time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.
中华眼镜蛇,是一种剧毒的眼镜蛇科蛇类,在中国南方地区导致相当高的发病率和死亡率。其毒液含有突触前 PLA 神经毒素(即β-金环蛇毒素)和突触后神经毒素(即α-金环蛇毒素)。我们研究了中华眼镜蛇毒液的体外神经毒性,以及特异性单价中华眼镜蛇抗蛇毒血清和澳大利亚多价抗蛇毒血清对毒液诱导的神经毒性的疗效。中华眼镜蛇毒液(1-10μg/ml)可消除鸡双颈肌神经-肌肉标本的间接抽搐,并减弱对外源性 ACh 和 CCh 的收缩反应,但对 KCl 无影响。这表明存在突触后神经毒性作用,但无明显肌毒性。由于突触后α-神经毒素的作用比突触前神经毒素更快,因此在后毒液中前者的活性将被掩盖。在加入中华眼镜蛇抗蛇毒血清(12 U/ml)或澳大利亚多价蛇抗蛇毒血清(15 U/ml)之前,毒液(3μg/ml)的神经毒性作用明显减弱,并防止对 ACh 和 CCh 的收缩反应的抑制。在加入中华眼镜蛇抗蛇毒血清(60 U/ml)或澳大利亚多价蛇抗蛇毒血清(50 U/ml)后,t 时间点后加入 3μg/ml 的中华眼镜蛇毒液,不能使抽搐高度在 180 分钟内恢复。在 t 或 t 时间点更早地加入 60 U/ml 的中华眼镜蛇抗蛇毒血清也不能预防毒液的神经毒性作用,但确实延迟了根据 t 值比较而消除抽搐的时间。从 t 时间点开始,用生理盐水反复冲洗标本,未能逆转毒液的神经毒性作用,也未能延迟消除抽搐的时间。本研究表明,中华眼镜蛇毒液在骨骼肌标本中显示出明显的体外神经毒性,而抗蛇毒血清不能逆转这种毒性。这似乎与抗蛇毒血清的疗效无关,而是由于神经毒素的不可逆/假性不可逆性质。