Department of Biochemistry & Molecular Biology, Monash University, Building 77, Clayton, VIC, 3800, Australia,
Neurotox Res. 2014 Apr;25(3):305-10. doi: 10.1007/s12640-013-9426-z. Epub 2013 Oct 16.
Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P < 0.0001). However, paradoxin induced a 32 % decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P < 0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.
太攀蛇是世界上最毒的蛇之一，神经毒性是这些蛇咬伤的主要危及生命的症状。有三种太攀蛇，每种蛇的毒液都含有一种突触前神经毒素，这是人类被蛇咬伤后观察到的大部分神经毒性的原因。用于治疗神经毒性的抗蛇毒血清成本高昂，因此需要开发替代但有效的治疗方法。因此，在这项研究中，我们研究了 P2Y 受体拮抗剂苏拉明预防三种太攀蛇毒液中突触前神经毒素（太攀蛇毒素、悖论毒素和卡尼毒素）在体外产生神经毒性的能力。毒素购自商业来源或使用多次凝胶过滤层析进行纯化。所有三种毒素（11 nM）在 300 分钟内抑制小鸡双颈椎神经-肌肉标本中的神经介导抽搐。苏拉明（0.3 mM）的存在完全阻断了太攀蛇毒素和卡尼毒素在实验过程中对神经介导抽搐的抑制（P < 0.0001）。然而，即使在 360 分钟内存在苏拉明，悖论毒素也会导致抽搐高度降低 32%。与单独使用毒素相比，这有显著差异（P < 0.0001）。我们还研究了苏拉明对 textilotoxin 和磷脂酶 A2 作用产物的神经毒性作用的影响。单独的每种毒素或在苏拉明存在的情况下均未能抑制外源性激动剂 ACh、CCh 或 KCl 的反应。我们的研究结果为旨在确定苏拉明在预防太攀蛇咬伤后神经毒性发作的疗效的临床研究提供了依据。
