Assessment of the Artemia salina toxicity assay as a substitute of the mouse lethality assay in the determination of venom-induced toxicity and preclinical efficacy of antivenom

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2024-04-03 DOI:10.1016/j.toxcx.2024.100195
Xavier Araya , Mitchel Okumu , Gina Durán , Aarón Gómez , José María Gutiérrez , Guillermo León
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Abstract

Mice are routinely used in snake venom research but are costly and subject to pain and suffering. The crustacean Artemia salina could be an alternative to mice, but data to support its adoption in snake venom research is limited. The aim of the present study was to evaluate the suitability of A. salina as a surrogate of mice in assessing the toxicity of venoms and the preclinical efficacy of antivenoms. The toxicity of venoms from 22 snakes of medical importance in sub–Saharan Africa was evaluated in mice (intraperitoneally; i.p. and intravenously; i.v.) and in A. salina. Subsequently, the capacity of a commercial antivenom to neutralize the toxicity of these venoms in mice and A. salina was investigated. There was a positive correlation between the i.v. median lethal doses (LD50s) and the i.p. LD50s in mice (r = 0.804; p < 0.0001), a moderate correlation between the i.v. LD50s in mice and the median lethal concentrations (LC50s) in A. salina (r = 0.606; p = 0.003), and a moderate correlation between the i.p. LD50s in mice and the LC50s in A. salina (r = 0.426; p = 0.048). Moreover, there was a strong correlation between the i.p. median effective doses (ED50s) and the i.v. ED50s in mice (r = 0.941, p < 0.0001), between the i.p. ED50s in mice and the ED50s in A. salina (r = 0.818, p < 0.0001), and between the i.v. ED50s in mice and the ED50s in A. salina (r = 0.972, p < 0.0001). These findings present A. salina as a promising candidate for reducing reliance on mice in snake venom research. Future investigations should build upon these findings, addressing potential limitations and expanding the scope of A. salina in venom research and antivenom development.

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在确定毒液引起的毒性和抗蛇毒血清的临床前疗效时,评估用盐水蒿毒性试验替代小鼠致死试验的效果
蛇毒研究通常使用小鼠,但小鼠成本高昂,而且会给研究人员带来痛苦。甲壳类动物盐蒿可以替代小鼠,但支持其用于蛇毒研究的数据有限。本研究的目的是评估在评估蛇毒的毒性和抗蛇毒血清的临床前疗效时,盐水蒿是否适合作为小鼠的替代品。研究人员在小鼠体内(腹腔注射和静脉注射)评估了撒哈拉以南非洲地区 22 种具有重要医疗价值的蛇的毒液的毒性,并在盐水蛙体内进行了评估。随后,研究了商用抗蛇毒血清中和这些毒液对小鼠和蝾螈毒性的能力。小鼠的静脉注射中位致死剂量(LD50s)与静脉注射 LD50s 之间呈正相关(r = 0.804; p < 0.0001),小鼠的静脉注射 LD50s 与静脉注射 LD50s 之间呈中度相关(r = 0.804; p < 0.0001)。小鼠的静脉注射半数致死剂量与盐藻类的中位致死浓度(LC50s)之间存在中度相关性(r = 0.606;p = 0.003),小鼠的口服半数致死剂量与盐藻类的 LC50s 之间存在中度相关性(r = 0.426;p = 0.048)。此外,小鼠口服中位有效剂量(ED50s)与静脉注射 ED50s 之间有很强的相关性(r = 0.941,p < 0.0001),小鼠口服 ED50s 与静脉注射 ED50s 之间也有很强的相关性(r = 0.941,p < 0.0001)。小鼠的静脉注射 ED50s 与盐肤木的 ED50s 之间(r = 0.818,p < 0.0001),以及小鼠的静脉注射 ED50s 与盐肤木的 ED50s 之间(r = 0.972,p < 0.0001)。这些研究结果表明,在蛇毒研究中,丹顶鹤有望减少对小鼠的依赖。未来的研究应以这些发现为基础,解决潜在的局限性,并扩大盐湖蛙在蛇毒研究和抗蛇毒血清开发中的应用范围。
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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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