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In-vitro Neurotoxicity of Two Malaysian Krait Species (Bungarus candidus and Bungarus fasciatus) Venoms: Neutralization by Monovalent and Polyvalent Antivenoms from Thailand

机译:两种马来西亚特有物种(Bungarus candidus和Bungarus fasciatus)毒液的体外神经毒性:泰国单价和多价抗毒液的中和作用

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Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.
机译:Bungarus candidus和Bungarus fasciatus是在东南亚发现的两种krait。这些蛇的毒害通常以神经毒性为特征,如果不进行治疗,会引起很高的发病率和死亡率。在这项研究中,在骨骼肌制剂中检查了每种物种的体外神经毒性,以及两个单价抗蛇毒药和多价抗蛇毒药对毒液的神经毒性作用的有效性。两种毒液均引起浓度依赖性的间接抽搐抑制,并在雏鸡biventer制剂中减弱了对外源性烟碱样受体激动剂的反应,其中念珠菌毒液比筋膜念珠菌毒液更有效。 SDS-PAGE和蛋白质印迹分析表明毒液之间的轮廓不同。尽管存在这些差异,但所有三个抗蛇毒血清都能识别大多数蛋白质条带。在毒液之前添加的抗毒液减弱了毒液的神经毒性作用。有趣的是,各自的一价抗蛇毒血清没有中和其他Bungarus物种的毒液作用,表明相对没有交叉中和作用。在添加毒液后的t 90 时间点添加高浓度的多价抗蛇毒液,可以部分逆转筋膜芽孢杆菌毒液的神经毒性,但不能逆转念珠菌毒液的神经毒性。在t 90 时间点添加时,一价抗蛇毒素无明显作用。这项研究表明,在鸡biventer制剂中,念珠芽孢杆菌和筋膜芽孢杆菌毒液均显示出明显的体外神经毒性,高剂量的抗蛇毒血清对预防或逆转神经毒性是必要的。

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