Department of Environmental Science, Baylor University, Waco, TX 76798, USA; Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX 76798 USA.
Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX 76798 USA; Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798, USA.
Environ Int. 2024 Nov;193:109045. doi: 10.1016/j.envint.2024.109045. Epub 2024 Oct 9.
Anatoxin-a is a globally occurring, yet understudied, chiral cyanobacterial toxin that threatens public health and the environment. It has led to numerous dog. livestock and bird poisonings and although it has been studied in rodent models, comparatively little research has occurred in aquatic species. To advance a comparative toxicology understanding of this toxin in alternative vertebrate models, developing zebrafish and fathead minnow were exposed to environmentally relevant and elevated levels (13-4400 μg/L) of (+) anatoxin-a to examine potential mortality and sublethal effects, including photolocomotor behavior and gene expression responses. We observed significantly higher mortality (p < 0.05) in fathead minnows exposed to ≥ 1400 μg/L (65 - 83 % survival versus 97 % in controls). Locomotor response profiles for zebrafish typically displayed hypoactivity after exposure to (+) anatoxin-a in both light and dark periods, while hyperactivity of fathead minnows was observed at the lowest treatment level, but only in light conditions. Gene expression in zebrafish was significantly (p < 0.05) downregulated for mbp, which is associated with myelin sheath formation, and elavl3, which is involved in neurogenesis, along with cyp3a65 and gst, two genes related to phase I and II metabolism. However, no significant (p > 0.05) transcriptional changes were observed in the fathead minnow model. These differential responses between commonly employed species employed as alternative vertebrate models in toxicology research and chemicals risk assessments highlight the need for more comparative studies to understand sensitivities and variations in organismal response. Furthermore, we identified higher mortality, refractory behavioral effects, and gene expression in (+) anatoxin-a exposed fish when compared to previously reported (±) anatoxin-a (racemic 50:50 enantiomer mixture) studies, which is frequently used as a surrogate chemical for experimental work. Our findings identify the importance of understanding species and enantiomer specific effects of natural toxins.
石房蛤毒素是一种在全球范围内存在但研究不足的手性蓝藻毒素，它威胁着公共健康和环境。它已经导致了许多狗。牲畜和鸟类中毒，尽管它已经在啮齿动物模型中进行了研究，但在水生物种中相对较少。为了在替代脊椎动物模型中推进对手性毒素的比较毒理学理解，开发了斑马鱼和褐鳟鱼，使其暴露于环境相关的和升高的水平（13-4400μg/L）的（+）石房蛤毒素，以检查潜在的死亡率和亚致死效应，包括光运动行为和基因表达反应。我们观察到暴露于≥1400μg/L（65-83%的存活率与对照组的 97%相比）的褐鳟鱼的死亡率显著升高（p<0.05）。斑马鱼暴露于（+）石房蛤毒素后的运动反应谱通常在光照和黑暗期都表现出低活性，而褐鳟鱼在最低处理水平下表现出兴奋，但仅在光照条件下。斑马鱼的 mbp（与髓鞘形成有关）和 elavl3（与神经发生有关）的基因表达显著下调（p<0.05），以及 cyp3a65 和 gst，这两个与 I 期和 II 期代谢有关的基因。然而，在褐鳟鱼模型中没有观察到显著的（p>0.05）转录变化。这些在毒理学研究和化学品风险评估中常用的替代脊椎动物模型之间的差异反应强调了进行更多比较研究以了解生物体反应的敏感性和变异性的必要性。此外，与之前报道的（±）石房蛤毒素（手性 50:50 对映体混合物）研究相比，我们发现暴露于（+）石房蛤毒素的鱼类死亡率更高、反射性行为效应更顽固，以及基因表达变化更大，而（±）石房蛤毒素通常被用作实验工作的替代化学物质。我们的研究结果确定了了解天然毒素的物种和对映体特异性效应的重要性。
