Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia; Centre for Molecular Development of Therapeutics, James Cook University, Cairns, Queensland, Australia.
Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
Toxicon. 2023 Sep;233:107250. doi: 10.1016/j.toxicon.2023.107250. Epub 2023 Aug 10.
Jellyfish envenomation is a global public health risk; Cubozoans (box jellyfish) are a prevalent jellyfish class with some species causing potent and potentially fatal envenomation in tropical Australian waters. Previous studies have explored the mechanism of action of venom from the lethal Cubozoan Chironex fleckeri and from Carukia barnesi (which causes "Irukandji syndrome"), but mechanistic knowledge to develop effective treatment is still limited. This study performed an in-vitro cytotoxic examination of the venoms of Chiropsella bronzie and Malo maxima, two understudied species that are closely related to Chironex fleckeri and Carukia barnesi respectively. Venom was applied to human skeletal muscle cells and human cardiomyocytes while monitoring with the xCELLigence system. Chiropsella bronzie caused rapid cytotoxicity at concentrations as low as 58.8 μg/mL. Malo maxima venom caused a notable increase in cell index, a measure of cell viability, followed by cytotoxicity after 24-h venom exposure at ≥11.2 μg/mL on skeletal muscle cells. In contrast, the cardiomyocytes mostly showed significant increased cell index at the higher M. maxima concentrations tested. These findings show that these venoms can exert cytotoxic effects and Malo maxima venom mainly caused a sustained increase in cell index across both human cell lines, suggesting a different mode of action to Chiropsella bronzie. As these venoms show different real-world envenomation symptoms, the different cellular toxicity profiles provide a first step towards developing improved understanding of mechanistic pathways and novel envenomation treatment.
水母蜇伤是一个全球性的公共健康风险；立方水母（箱形水母）是一种普遍存在的水母类群，其某些物种在澳大利亚热带水域会导致严重且潜在致命的蜇伤。以前的研究已经探索了致命立方水母 Chironex fleckeri 和 Carukia barnesi（引起“伊鲁坎吉综合征”）毒液的作用机制，但开发有效治疗方法的机制知识仍然有限。本研究对 Chiropsella bronzie 和 Malo maxima 的毒液进行了体外细胞毒性检查，这两种研究较少的物种分别与 Chironex fleckeri 和 Carukia barnesi 密切相关。在监测 xCELLigence 系统的同时，将毒液应用于人类骨骼肌细胞和人心肌细胞。Chiropsella bronzie 在低至 58.8μg/mL 的浓度下即可迅速引起细胞毒性。Malo maxima 毒液在 24 小时毒液暴露后，在骨骼肌细胞上≥11.2μg/mL 时会引起细胞指数（细胞活力的衡量指标）显著增加，随后出现细胞毒性。相比之下，较高浓度的 Malo maxima 在测试的人心肌细胞中主要表现出显著增加的细胞指数。这些发现表明这些毒液可以发挥细胞毒性作用，而 Malo maxima 毒液主要在两种人类细胞系中引起细胞指数的持续增加，表明与 Chiropsella bronzie 的作用机制不同。由于这些毒液在现实世界中引起不同的蜇伤症状，不同的细胞毒性特征为深入了解机制途径和新型蜇伤治疗提供了第一步。
