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Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay

机译:Tityus serrulatus蝎毒:体外测试及其与体内致死剂量测定的相关性

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摘要

Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO) recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD50 determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD50 results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase chromatographic profiles also has a potential application in venoms’ quality control, as there were fewer neurotoxins detected in the venom with high LD50 value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD50 assay to evaluate the venom excellence by discriminating—and discarding—poor-quality batches, and, consequently, with a positive impact on the number of animals used. Notably, proposed assays are fast and inexpensive, being technically and economically feasible in Tityus serrulatus venom quality control to produce effective antivenoms.
机译:在巴西,蝎子are伤是人类被人毒化的主要原因,世界卫生组织(世卫组织)建议使用抗蛇毒毒素来治疗受害者。要获得有效的抗蛇毒血清,第一步是使用高质量的毒液池并对其进行评估,其中最常用的方法是LD50测定。但是,这很耗时,并且需要高级技术培训。此外,关于测试所需的动物数量存在重大的伦理问题。因此,我们研究了LD50结果,体外测定之间的对应关系,并观察到了与蛋白水解活性水平的强相关性,从而显着地表明,蛋白酶是潜在的毒副反应。反相色谱图的比较在毒液的质量控制中也有潜在的应用,因为在毒液中检测到的神经毒素较少,LD50值较高。质谱分析证实了这些结果。因此,这些方法可以在LD50分析之前通过区分和丢弃劣质批次来评估毒液的卓越性,从而对所用动物的数量产生积极影响。值得注意的是,提出的测定是快速且便宜的,在Tityus serrulatus毒液质量控制中在技术和经济上是可行的,以产生有效的抗毒液。

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