Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Toxins (Basel). 2024 Mar 1;16(3):124. doi: 10.3390/toxins16030124.
The heterogeneity in venom composition and potency in disparate Eastern Russell's viper () populations has repercussions for the efficacy of antivenoms. This is particularly pronounced in geographical areas in which the venom of the local species has not been well studied and locally produced antivenoms are unavailable. In such cases, alternative therapies following envenoming, which are not limited by species specificity, may be employed to complement antivenoms. We studied the neuromuscular activity of venom from Thailand and Java (Indonesia) and the ability of Thai antivenoms and/or Varespladib to prevent or reverse these effects. Both Thai and Javanese venoms displayed potent pre-synaptic neurotoxicity but weak myotoxicity in the chick biventer cervicis nerve-muscle preparation. Whilst the neurotoxicity induced by both venoms was abolished by the prior administration of Thai monovalent antivenom or pre-incubation with Varespladib, Thai neuro-polyvalent antivenom only produced partial protection when added prior to venom. Pre-synaptic neurotoxicity was not reversed by the post-venom addition of either antivenom 30 or 60 min after either venom. Varespladib, when added 60 min after venom, prevented further inhibition of indirect twitches. However, the subsequent addition of additional concentrations of Varespladib did not result in further recovery from neurotoxicity. The combination of Thai monovalent antivenom and Varespladib, added 60 min after venom, resulted in additional recovery of twitches caused by either Thai or Javanese venoms compared with antivenom alone. In conclusion, we have shown that Varespladib can prevent and partially reverse the pre-synaptic neurotoxicity induced by either Thai or Javanese venoms. The efficacy of Thai monovalent antivenom in reversing pre-synaptic neurotoxicity was significantly enhanced by its co-administration with Varespladib. Further work is required to establish the efficacy of Varespladib as a primary or adjunct therapy in human envenoming.
在不同地区的东部圆斑蝰（）种群中，毒液组成和效力存在异质性，这对抗蛇毒血清的疗效有影响。在当地物种的毒液尚未得到充分研究且无法生产当地抗蛇毒血清的地理区域，这种影响尤为明显。在这种情况下，可采用不受物种特异性限制的替代疗法来补充抗蛇毒血清。我们研究了来自泰国和爪哇（印度尼西亚）的毒液的神经肌肉活性，以及泰国抗蛇毒血清和/或 Varespladib 预防或逆转这些作用的能力。泰国和爪哇的毒液在鸡二腹肌颈神经-肌肉标本中均表现出强大的突触前神经毒性，但肌肉毒性较弱。虽然两种毒液诱导的神经毒性均被泰国单价抗蛇毒血清预先给药或与 Varespladib 预孵育所消除，但当在毒液之前添加时，泰国神经多价抗蛇毒血清仅产生部分保护作用。在毒液后添加抗蛇毒血清 30 或 60 分钟后，均不能逆转突触前神经毒性。Varespladib 在毒液后 60 分钟添加可防止间接抽搐进一步抑制。然而，随后添加更高浓度的 Varespladib 并不能进一步从神经毒性中恢复。与单独使用抗蛇毒血清相比，在毒液后 60 分钟添加泰国单价抗蛇毒血清和 Varespladib 可使两种毒液引起的抽搐进一步恢复。总之，我们已经表明，Varespladib 可以预防和部分逆转泰国或爪哇毒液诱导的突触前神经毒性。Varespladib 与泰国单价抗蛇毒血清联合使用可显著增强其逆转突触前神经毒性的功效。需要进一步的工作来确定 Varespladib 作为人类蛇咬伤的主要或辅助治疗的疗效。
