Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
Pharmacol Ther. 2021 Nov;227:107865. doi: 10.1016/j.pharmthera.2021.107865. Epub 2021 Apr 28.
Domoic acid (DA), the causative agent for the human syndrome Amnesic Shellfish Poisoning (ASP), is a potent, naturally occurring neurotoxin produced by common marine algae. DA accumulates in seafood, and humans and wildlife alike can subsequently be exposed when consuming DA-contaminated shellfish or finfish. While strong regulatory limits protect people from the acute effects associated with ASP, DA is an increasingly significant public health concern, particularly for coastal dwelling populations, and there is a growing body of evidence suggesting that there are significant health consequences following repeated exposures to levels of the toxin below current safety guidelines. However, gaps in scientific knowledge make it difficult to precisely determine the risks of contemporary low-level exposure scenarios. The present review characterizes the toxicokinetics and neurotoxicology of DA, discussing results from clinical and preclinical studies after both adult and developmental DA exposure. The review also highlights crucial areas for future DA research and makes the case that DA safety limits need to be reassessed to best protect public health from deleterious effects of this widespread marine toxin.
软骨藻酸(DA)是一种强效的天然神经毒素,由常见的海洋藻类产生,是导致人类健忘性贝类中毒(ASP)的病原体。DA 在海产品中积累,如果人类和野生动物食用了受 DA 污染的贝类或鳍鱼,就会受到污染。虽然强有力的监管限制可以保护人们免受与 ASP 相关的急性影响,但 DA 越来越成为一个重要的公共卫生问题,特别是对于沿海居住的人群,越来越多的证据表明,在当前安全指南以下的水平反复暴露于这种毒素会对健康造成严重后果。然而,科学知识的差距使得很难准确确定当代低水平暴露情况的风险。本综述描述了 DA 的毒代动力学和神经毒理学,讨论了成年和发育中的 DA 暴露后临床和临床前研究的结果。该综述还突出了未来 DA 研究的关键领域,并认为需要重新评估 DA 的安全限制,以最佳保护公众健康免受这种广泛存在的海洋毒素的有害影响。