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). 2023 Jan 11;15(1):62. doi: 10.3390/toxins15010062.
The venom of the Russell's viper () contains neurotoxic and myotoxic phospholipase A toxins which can cause irreversible damage to motor nerve terminals. Due to the time delay between envenoming and antivenom administration, antivenoms may have limited efficacy against some of these venom components. Hence, there is a need for adjunct treatments to circumvent these limitations. In this study, we examined the efficacy of Chinese antivenom alone, and in combination with a PLA inhibitor, Varespladib, in reversing the in vitro neuromuscular blockade in the chick biventer cervicis nerve-muscle preparation. Pre-synaptic neurotoxicity and myotoxicity were not reversed by the addition of Chinese antivenom 30 or 60 min after venom (10 µg/mL). The prior addition of Varespladib prevented the neurotoxic and myotoxic activity of venom (10 µg/mL) and was also able to prevent further reductions in neuromuscular block and muscle twitches when added 60 min after venom. The addition of the combination of Varespladib and antivenom 60 min after venom failed to produce further improvements than Varespladib alone. This demonstrates that the window of time in which antivenom remains effective is relatively short compared to Varespladib and small-molecule inhibitors may be effective in abrogating some activities of Chinese venom.
圆斑蝰蛇()的毒液含有神经毒性和肌毒性的磷脂酶 A 毒素,可对运动神经末梢造成不可逆转的损伤。由于毒蛇咬伤和抗蛇毒血清治疗之间存在时间延迟,抗蛇毒血清可能对抗这些毒液成分的效果有限。因此,需要辅助治疗来规避这些限制。在这项研究中,我们研究了单独使用中国抗蛇毒血清,以及与 PLA 抑制剂瓦瑞普拉德(Varespladib)联合使用,在小鸡双颈肌神经-肌肉标本中逆转体外神经肌肉阻滞的效果。在添加 10 µg/mL 毒液后 30 或 60 分钟添加中国抗蛇毒血清并不能逆转毒蕈碱样前突触神经毒性和肌毒性。在添加瓦瑞普拉德之前,可预防毒液(10 µg/mL)的神经毒性和肌毒性活性,并且当在添加毒液 60 分钟后添加时,也能够防止神经肌肉阻滞和肌肉抽搐的进一步减少。在添加毒液 60 分钟后添加瓦瑞普拉德和抗蛇毒血清的组合并未产生比单独使用瓦瑞普拉德更好的效果。这表明与瓦瑞普拉德相比,抗蛇毒血清有效的时间窗口相对较短,并且小分子抑制剂可能有效消除中国蛇毒的某些活性。