Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia.
Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia.
Comp Biochem Physiol C Toxicol Pharmacol. 2022 Jun;256:109326. doi: 10.1016/j.cbpc.2022.109326. Epub 2022 Mar 4.
The viperid snake genus Bothriechis consists of eleven species distributed among Central and South America, living across low and high-altitude habitats. Despite Bothriechis envenomations being prominent across the Central and South American region, the functional effects of Bothriechis venoms are poorly understood. Thus, the aim of this study was to investigate the coagulotoxic and neurotoxic activities of Bothriechis venoms to fill this knowledge gap. Coagulotoxic investigations revealed Bothriechis nigroviridis and B. schlegelii to have pseudo-procoagulant venom activity, forming weak clots that rapidly break down, thereby depleting fibrinogen levels and thus contributing to a net anticoagulant state. While one sample of B. lateralis also showed weaker pseudo-procoagulant activity, directly clotting fibrinogen, two samples of B. lateralis venom were anticoagulant through the inhibition of thrombin and factor Xa activity. Differential efficacy of PoliVal-ICP antivenom was also observed, with the pseudo-procoagulant effect of B. nigroviridis venom poorly neutralised, despite this same activity in the venom of B. schlegelii being effectively neutralised. Significant specificity of these fibrinogen cleaving toxins was also observed, with no activity upon model amphibian, avian, lizard or rodent plasma observed. However, upon avian plasma the venom of B. nigroviridis exerted a complete anticoagulant effect, in contrast to the pseudo-procoagulant effect seen on human plasma. Neurotoxic investigations revealed B. schlegelii to be unique among the genus in having potent binding to the orthosteric site of the alpha-1 postsynaptic nicotinic acetylcholine receptor (with B. lateralis having a weaker but still discernible effect). This represents the first identification of postsynaptic nAChR neurotoxic activity for Bothriechis. In conclusion this study identifies notable differential activity within the coagulotoxic and postsynaptic neurotoxic activity of Bothriechis venoms, supporting previous research, and highlights the need for further studies with respect to antivenom efficacy as well as coagulotoxin specificity for Bothriechis venoms.
毒蛇属 Bothriechis 包括分布在中美洲和南美洲的 11 个物种，生活在低海拔和高海拔栖息地。尽管 Bothriechis 蛇毒在中美洲和南美洲地区很突出，但 Bothriechis 毒液的功能影响却知之甚少。因此，本研究的目的是研究 Bothriechis 毒液的凝血毒性和神经毒性活性，以填补这一知识空白。凝血毒性研究表明，Bothriechis nigroviridis 和 B. schlegelii 具有伪促凝毒液活性，形成较弱的血栓，迅速分解，从而耗尽纤维蛋白原水平，从而导致净抗凝状态。虽然一个 B. lateralis 样本也显示出较弱的伪促凝活性，直接凝固纤维蛋白原，但 B. lateralis 毒液的两个样本通过抑制凝血酶和因子 Xa 活性而具有抗凝作用。还观察到 PoliVal-ICP 抗蛇毒血清的疗效差异，尽管 B. schlegelii 毒液中的这种相同活性得到了有效中和，但 B. nigroviridis 毒液的伪促凝作用却没有得到很好的中和。这些纤维蛋白原裂解毒素的特异性也很显著，在模型两栖动物、鸟类、蜥蜴或啮齿动物血浆中观察不到活性。然而，在禽类血浆中，B. nigroviridis 毒液发挥了完全的抗凝作用，与在人血浆中观察到的伪促凝作用形成对比。神经毒性研究表明，B. schlegelii 在该属中是独特的，因为它对α-1 突触后烟碱型乙酰胆碱受体的正位结合具有很强的作用（B. lateralis 的作用较弱，但仍然可以分辨）。这是首次鉴定 Bothriechis 的突触后 nAChR 神经毒性活性。总之，本研究确定了 Bothriechis 毒液在凝血毒性和突触后神经毒性活性方面存在显著的差异活性，支持了先前的研究，并强调了进一步研究 Bothriechis 毒液的抗蛇毒血清疗效以及凝血毒素特异性的必要性。
