Instituto Clodomiro Picado, Facultad de Microbiología, San José, Costa Rica.
Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica.
Front Immunol. 2021 Jan 11;11:617429. doi: 10.3389/fimmu.2020.617429. eCollection 2020.
There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between toxicity tests and surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A), (d) coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity , (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new alternatives and more 'humane' experimental designs will emerge in this field.
在毒理学研究中使用实验动物以及评估蛇抗蛇毒血清的中和效果时，非常有必要加强实施 3R 原则（替代、减少和优化）。由于蛇毒液的固有复杂性，这是一项具有挑战性的任务。本文对这一主题的最新研究进展进行了综述，重点介绍了在毒性测试和替代测试之间观察到相关性的研究，特别是在毒液致死活性及其中和作用的研究中。当使用以下方法时，已经描述了一些毒液-抗蛇毒血清之间的相关性：（a）酶免疫测定，（b）血凝，（c）酶测定（蛋白酶、磷脂酶 A），（d）对血浆的凝固作用，（e）细胞培养测定细胞毒性，（f）用于评估神经毒性的功能测定，（g）使用母鸡的鸡蛋，（h）抗蛇毒血清组学。此外，还在这些检测中常规引入镇痛，并为致死性检测设计更“人道”的方案。预计未来几年将越来越意识到 3R 原则在抗蛇毒血清检测中的相关性，并且该领域将出现新的替代方法和更“人道”的实验设计。
