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墨西哥医学相关响尾蛇属物种的毒理学特征及其响尾蛇属/矛头蝮属抗蛇毒血清的中和作用

Toxicological profile of medically relevant Crotalus species from Mexico and their neutralization by a Crotalus basiliscus/Bothrops asper antivenom.

机构信息

Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.

Laboratorios de Biológicos y Reactivos de México S.A. de C.V. (BIRMEX), México DF, Mexico.

出版信息

Toxicon. 2020 May;179:92-100. doi: 10.1016/j.toxicon.2020.03.006. Epub 2020 Mar 18.

Abstract

Specimens of the Crotalus genus represent a potential snakebite problem in Mexico, and despite the great number of species of Crotalus present in this country, only a few of them are relevant from a medical point of view. Crotalus envenomed patients can present a range of signs and symptoms, depending on the species involved, and their treatment is indistinctly with either of the anti-viperid antivenoms available in the Mexican Public Health System. One of these antivenoms is produced by immunization of horses with a mixture of only two venoms: Crotalus basiliscus and Bothrops asper venoms. In light of the high variability found in Crotalus species venom composition, it is important to demonstrate the cross-neutralization of this antivenom against other Crotalus species. Therefore, in this work the toxic variability of eight medically important Crotalus venoms from Mexico and its neutralization by the Crotalus basiliscus/Bothrops asper antivenom were assessed. The present study evidenced the variability of toxic and enzymatic activities among the following Crotalus venoms: (1) Crotalus atrox, (2) Crotalus basiliscus, (3) Crotalus culminatus, (4) Crotalus simus, (5) Crotalus tzabcan, (6) Crotalus scutulatus salvini, (7) Crotalus scutulatus scutulatus-A, and (8) Crotalus scutulatus scutulatus-B. All venoms studied possess lethal and hemorrhagic activity on a murine model, although there are important variations among the species; in contrast, the PLA activity was similar for all venoms. Interestingly, only C. simus venom exhibited coagulant activity on human plasma under 100 μg. The antivenom neutralized the lethality and all the other assessed activities for all venoms tested. However, the dose required varied depending on the venom and the evaluated activity. Our preclinical data support the recommendation of using this antivenom to clinically manage Crotalus snakebites produced by the species assessed in this study. Nonetheless, only clinical trials could categorically validate these results.

摘要

响尾蛇属的标本代表了墨西哥潜在的蛇咬伤问题,尽管该国存在大量响尾蛇物种,但从医学角度来看,只有少数几种是相关的。被响尾蛇咬伤的患者可能会出现一系列症状和体征,具体取决于涉及的物种,而它们的治疗方法是使用墨西哥公共卫生系统中提供的任何一种抗蝮蛇抗蛇毒血清。其中一种抗蛇毒血清是通过用两种毒液混合免疫马制成的:矛头蝮蛇和矛头蝮蛇毒液。鉴于响尾蛇毒液成分的高度变异性,证明这种抗蛇毒血清对其他响尾蛇物种的交叉中和作用非常重要。因此,在这项工作中,评估了来自墨西哥的八种具有重要医学意义的响尾蛇毒液的毒性变异性及其对矛头蝮蛇/矛头蝮蛇抗蛇毒血清的中和作用。本研究证明了以下响尾蛇毒液的毒性和酶活性的可变性:(1)响尾蛇atrox,(2)矛头蝮蛇 basiliscus,(3)响尾蛇 culminatus,(4)响尾蛇 simus,(5)响尾蛇 tzabcan,(6)响尾蛇 scutulatus salvini,(7)响尾蛇 scutulatus scutulatus-A,和(8)响尾蛇 scutulatus scutulatus-B。所有研究的毒液在小鼠模型中都具有致死性和出血活性,尽管物种之间存在重要差异;相反,所有毒液的 PLA 活性相似。有趣的是,只有 C. simus 毒液在 100μg 下对人血浆表现出凝血活性。抗蛇毒血清中和了所有测试毒液的致死性和所有其他评估的活性。然而,所需的剂量取决于毒液和评估的活性。我们的临床前数据支持使用这种抗蛇毒血清来临床治疗本研究中评估的物种引起的响尾蛇咬伤的建议。然而,只有临床试验才能明确验证这些结果。

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