评估肯尼亚大棕色吐痰眼镜蛇(Naja ashei)毒液的致死性和细胞毒性作用,以及选定的商业抗蛇毒血清的毒中和效果

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2022-06-01 DOI:10.1016/j.toxcx.2022.100125
Ernest Z. Manson , Mutinda C. Kyama , Joseph K. Gikunju , Josephine Kimani , James H. Kimotho
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引用次数: 2

摘要

临床前小鼠模型的致死中和已被世界卫生组织确立为评价抗蛇毒血清疗效的金标准。对抗蛇毒血清中和特性的评估有助于辨别这些抗蛇毒血清在中和由医学上重要的蛇毒引起的毒性作用方面的功效。然而,对于许多抗蛇毒血清,关于其临床前疗效的信息仍然有限。因此,为了加强全球减少蛇咬伤影响的努力,提供关于抗蛇毒血清临床前疗效的信息至关重要,特别是在世界上抗蛇毒血清可得性和可及性存在问题的地区,包括撒哈拉以南非洲。本研究提出了致命的和有毒的活动N. ashei蛇毒和中和能力的两种常用的商业抗蛇毒在肯尼亚;VINS™和Inoserp™。在小鼠实验中,评价了灰头蛇毒的中位致死剂量(LD50)、最小坏死剂量(MND)和最小水肿形成剂量(MED)及其中和作用。毒的LD50为4.67 (3.34 ~ 6.54)mg/kg, MND和MED分别为11.00和0.80 μg。VINS™和Inoserp™抗蛇毒血清均显示有能力中和由Naja ashei毒液引起的致命和毒性作用,尽管效果不同。因此,我们的研究结果证实了以前在其他Naja sp.毒液中观察到的ashei N.毒液的毒性作用,并强调了抗蛇毒血清在抗蛇毒血清设计中的准特异性中和能力的相关性。
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Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya

Neutralization of lethality in mice model at the preclinical level has been established by the World Health Organization as the gold standard for the evaluation of antivenom efficacy. The assessment of the neutralization profiles of antivenoms helps to discern the efficacy or otherwise of these antivenoms at neutralizing the toxic effects induced by medically significant snake venoms. However, for many antivenoms, information on their preclinical efficacy remains limited. Therefore, to strengthen global efforts at reducing the impact of snakebite envenoming, the provision of information on the preclinical efficacy of antivenoms, especially in parts of the world where antivenom availability and accessibility is problematic, including sub-Saharan Africa is crucial. This study presents the lethal and toxic activities of N. ashei venom and the neutralizing capacity of two commonly used commercial antivenoms in Kenya; VINS™ and Inoserp™. Median lethal dose (LD50), minimum necrotizing dose (MND) and minimum edema-forming dose (MED) of N. ashei venom as well as the neutralization of these effects were evaluated in mice. The LD50 of N. ashei venom was found to be 4.67 (3.34–6.54) mg/kg while MND and MED were 11.00 μg and 0.80 μg respectively. Both VINS™ and Inoserp™ antivenoms demonstrated capacity to neutralize the lethal and toxic effects induced by Naja ashei venom albeit at varying efficacies. Our results thus confirm the toxic effects of N. ashei venom as previously observed with other Naja sp. venoms and also underscore the relevance of para-specific neutralizing capacity of antivenoms in the design of antivenoms.

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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
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