Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.
Unusual Pet Vets, Jindalee, QLD, 4074, Australia.
Toxicon. 2022 Sep;216:37-44. doi: 10.1016/j.toxicon.2022.06.012. Epub 2022 Jun 30.
Venom is a key evolutionary innovation which plays a primary role in prey subjugation by venomous snakes. However, while there is a growing body of literature indicating the composition and activity of snake venoms is under strong natural selection driven by differences in prey physiology, the majority of studies have historically focussed on the activity of snake venoms with regards only towards human or mammalian physiologies. This study aimed to use clotting assays measuring both time and strength of clotting to characterise the coagulotoxic activity of venoms from a taxonomically, morphologically, and ecologically diverse range of Bitis spp. of viperid snakes upon the plasma of model species: amphibian (Cane Toad, Rhinella marina); lizard (Blue-tongue Skink, Tiliqua scincoides); avian (Domestic Chicken, Gallus gallus); and rodent (Brown Rat, Rattus norvegicus). Significant variation in coagulotoxic activity across the different plasmas was observed between species and compared to the known affects upon human plasma. Bitis caudalis was notable in being active on all four plasmas, but in extremely divergent manners: accelerating clotting times and producing strong, stable clots upon amphibian plasma (consistent with true procoagulation); accelerating clotting time but producing weak, unstable clots upon lizard plasma (consistent with pseudo-procoagulation); delaying avian clotting time beyond machine maximum reading time (strong anticoagulation consistent with either inhibition of clotting enzymes or total destruction of fibrinogen, or both); and delaying clotting of rodent plasma (consistent with inhibition of clotting enzymes) and with only weak clots formed (consistent with destruction of fibrinogen). In contrast, the sister species B. peringueyi and B. schneideri displayed activity only upon the lizard plasma, slightly accelerating the clotting times to produce weak, unstable clots (consistent with pseudo-procoagulation). The other dwarf species, B. cornuta, displayed strong anticoagulation upon avian and rodent plasmas, delaying clotting beyond the machine maximum reading time (strong anticoagulation consistent with either inhibition of clotting enzymes or total destruction of fibrinogen, or both). In contrast, the giant species studied (B. gabonica) showed only a very weak pseudo-procoagulant activity upon lizard plasma. The wide range of variation seen within this study highlights the importance of studying venom activity on relevant models when making conclusions about the ecological role of venoms and the extreme limitation in extrapolating animal results to predict potential human clinical effects.
毒液是一种关键的进化创新，在毒蛇捕食中起着主要作用。然而，尽管越来越多的文献表明，蛇毒液的组成和活性受到猎物生理学差异的强烈自然选择的驱动，但大多数研究历史上只关注仅针对人类或哺乳动物生理学的蛇毒液活性。本研究旨在使用凝血测定法测量凝血时间和强度，以表征来自形态学和生态学上多样化的角蝰属（Viperidae 蛇）的毒液在模型物种血浆中的凝血毒性：两栖动物（蟾蜍，Rhinella marina）；蜥蜴（蓝舌石龙子，Tiliqua scincoides）；鸟类（家鸡，Gallus gallus）；和啮齿动物（褐鼠，Rattus norvegicus）。观察到不同物种之间的凝血毒性在不同的血浆中有显著的差异，并与对人类血浆的已知影响进行了比较。Bitis caudalis 在所有四种血浆中都表现出活性，但方式非常不同：在两栖动物血浆中加速凝血时间并产生强而稳定的血栓（与真正的促凝一致）；在蜥蜴血浆中加速凝血时间但产生弱而不稳定的血栓（与假性促凝一致）；使禽类的凝血时间超过机器的最大读数时间（强烈的抗凝作用一致，可能是由于凝血酶抑制剂或纤维蛋白原的完全破坏，或两者兼而有之）；并延迟啮齿动物血浆的凝血时间（与凝血酶抑制剂一致），并且仅形成弱血栓（与纤维蛋白原破坏一致）。相比之下，姐妹种 B. peringueyi 和 B. schneideri 仅在蜥蜴血浆中表现出活性，略微加速凝血时间以产生弱而不稳定的血栓（与假性促凝一致）。其他矮种，B. cornuta，在禽类和啮齿动物的血浆中表现出强烈的抗凝作用，使凝血时间超过机器的最大读数时间（强烈的抗凝作用一致，可能是由于凝血酶抑制剂或纤维蛋白原的完全破坏，或两者兼而有之）。相比之下，研究中的巨型物种（B. gabonica）仅在蜥蜴血浆中表现出非常弱的假性促凝血活性。本研究中观察到的广泛变异突出表明，在得出关于毒液生态作用的结论时，在相关模型上研究毒液活性非常重要，并且将动物结果外推以预测潜在的人类临床影响具有极大的局限性。
