破坏肌肉:中美洲蛇毒的神经毒性和肌毒性作用以及抗蛇毒血清和伐雷司他啶的相对疗效。

IF 4.4 1区 生物学 Q1 BIOLOGY
Lee Jones, Mimi Lay, Edgar Neri-Castro, Vanessa Zarzosa, Wayne C Hodgson, Matthew Lewin, Bryan G Fry
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引用次数: 0

摘要

背景:蛇属 Atropoides、Cerrophidion 和 Metlapilcoatlus 是分布于墨西哥和中美洲的新热带蝮蛇支系。本研究评估了九种 Atropoides、Cerrophidion 和 Metlapilcoatlus 的肌毒性和神经毒性效应,以及哥斯达黎加生产的 ICP 抗蛇毒血清对这些效应的中和效果。鉴于 PLA2 在这些物种的毒液蛋白质组中的显著地位,我们还旨在确定 PLA2 抑制剂 varespladib 的中和效力:结果:所有毒液都显示出肌毒性和潜在的神经毒性作用,不同毒液种内和种间的效力不同。抗蛇毒血清中和所观察到的肌肉损伤性病理生理效应的能力也存在这种差异。对 PLA2 抑制剂 varespladib 的相对反应也存在差异。虽然varespladib能有效中和M. mexicanus和M. nummifer毒液的肌毒性效应,表明肌毒性是由PLA2介导的,但C. godmani和M. olmec毒液的肌毒性效应却没有被中和,这表明肌毒性是由非PLA2毒素类型驱动的:本研究揭示了美洲黄鼠狼的肌毒性和神经毒性毒液活性以及Atropoides、Cerrophidion和Metlapilcoatlus支系毒液的中和效应。我们的研究结果为研究较少的蛇类支系提供了重要的临床和进化知识。此外,这些结果还为今后研究生态位特化与毒液进化之间的相互影响提供了一个平台,同时也强调了测试纯化毒素的必要性,以便准确评估在这些毒液中观察到的潜在影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Breaking muscle: neurotoxic and myotoxic effects of Central American snake venoms and the relative efficacies of antivenom and varespladib.

Background: The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib.

Results: All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types.

Conclusions: This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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