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抗蛇毒血清对死亡蝰蛇(棘蛇属)毒液体外神经毒性作用的有效性的物种和区域差异。

Species and regional variations in the effectiveness of antivenom against the in vitro neurotoxicity of death adder (Acanthophis) venoms.

作者信息

Fry B G, Wickramaratna J C, Jones A, Alewood P F, Hodgson W C

机构信息

The Centre for Drug Design and Development, University of Queensland, St. Lucia, Queensland, 4072, Australia.

出版信息

Toxicol Appl Pharmacol. 2001 Sep 1;175(2):140-8. doi: 10.1006/taap.2001.9233.

DOI:10.1006/taap.2001.9233
PMID:11543646
Abstract

Although viperlike in appearance and habit, death adders belong to the Elapidae family of snakes. Systemic envenomation represents a serious medical problem with antivenom, which is raised against Acanthophis antarcticus venom, representing the primary treatment. This study focused on the major Acanthophis variants from Australia and islands in the Indo-Pacific region. Venoms were profiled using liquid chromatography-mass spectrometry, and analyzed for in vitro neurotoxicity (0.3-10 microg/ml), as well as the effectiveness of antivenom (1-5 units/ml; 10 min prior to the addition of 10 microg/ml venom). The following death adder venoms were examined: A. antarcticus (from separate populations in New South Wales, Queensland, South Australia, and Western Australia), A. hawkei, A. praelongus, A. pyrrhus, A. rugosus, A. wellsi, and venom from an unnamed species from the Indonesian island of Seram. All venoms abolished indirect twitches of the chick isolated biventer cervicis nerve-muscle preparation in a dose-dependent manner. In addition, all venoms blocked responses to exogenous acetylcholine (1 mM) and carbachol (20 microM), but not KCl (40 mM), suggesting postsynaptic neurotoxicity. Death adder antivenom (1 unit/ml) prevented the neurotoxic effects of A. pyrrhus, A. praelongus, and A. hawkei venoms, although it was markedly less effective against venoms from A. antarcticus (NSW, SA, WA), A. rugosus, A. wellsi, and A. sp. Seram. However, at 5 units/ml, antivenom was effective against all venoms tested. Death adder venoms, including those from A. antarcticus geographic variants, differed not only in their venom composition but also in their neurotoxic activity and susceptibility to antivenom. For the first time toxicological aspects of A. hawkei, A. wellsi, A. rugosus, and A. sp. Seram venoms were studied.

摘要

尽管死亡蝮蛇在外观和习性上类似蝰蛇,但它们属于眼镜蛇科。全身性蛇毒中毒是一个严重的医学问题,抗蛇毒血清是主要治疗手段,该抗蛇毒血清是针对南部棘蛇毒液制备的。本研究聚焦于来自澳大利亚以及印度 - 太平洋地区岛屿的主要南部棘蛇变种。使用液相色谱 - 质谱联用技术对毒液进行分析,并检测其体外神经毒性(0.3 - 10微克/毫升)以及抗蛇毒血清的效果(1 - 5单位/毫升;在加入10微克/毫升毒液前10分钟)。检测了以下死亡蝮蛇的毒液:南部棘蛇(分别来自新南威尔士州、昆士兰州、南澳大利亚州和西澳大利亚州的不同种群)、霍氏死亡蝮蛇、长吻死亡蝮蛇、红腹死亡蝮蛇、多皱死亡蝮蛇、韦氏死亡蝮蛇,以及来自印度尼西亚塞兰岛一种未命名物种的毒液。所有毒液均以剂量依赖方式消除了雏鸡离体颈二腹肌神经 - 肌肉标本的间接抽搐。此外,所有毒液均阻断了对外源性乙酰胆碱(1毫摩尔/升)和卡巴胆碱(20微摩尔/升)的反应,但不阻断对氯化钾(40毫摩尔/升)的反应,提示存在突触后神经毒性。死亡蝮蛇抗蛇毒血清(1单位/毫升)可预防红腹死亡蝮蛇、长吻死亡蝮蛇和霍氏死亡蝮蛇毒液的神经毒性作用,不过对来自新南威尔士州、南澳大利亚州、西澳大利亚州的南部棘蛇、多皱死亡蝮蛇、韦氏死亡蝮蛇以及塞兰岛未命名物种的毒液效果明显较差。然而,抗蛇毒血清浓度为5单位/毫升时,对所有测试毒液均有效。死亡蝮蛇毒液,包括来自南部棘蛇不同地理变种的毒液,不仅在毒液成分上存在差异,在神经毒性活性以及对抗蛇毒血清的敏感性方面也有所不同。本研究首次对霍氏死亡蝮蛇、韦氏死亡蝮蛇、多皱死亡蝮蛇以及塞兰岛未命名物种毒液的毒理学方面进行了研究。

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