Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Center on Human Development and Disability, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
Neurotoxicol Teratol. 2019 Mar-Apr;72:10-21. doi: 10.1016/j.ntt.2019.01.001. Epub 2019 Jan 5.
Domoic Acid (DA) is a naturally-occurring excitotoxin, produced by marine algae, which can bioaccumulate in shellfish and finfish. The consumption of seafood contaminated with DA is associated with gastrointestinal illness that, in the case of high DA exposure, can evolve into a spectrum of responses ranging from agitation to hallucinations, memory loss, seizures and coma. Because algal blooms that produce DA are becoming more widespread and very little is known about the dangers of chronic, low-dose exposure, we initiated a preclinical study focused on the reproductive and developmental effects of DA in a nonhuman primate model. To this end, 32 adult female Macaca fascicularis monkeys were orally exposed to 0, 0.075 or 0.15 mg/kg/day DA on a daily basis, prior to and during pregnancy. Females were bred to non-exposed males and infants were evaluated at birth. Results from this study provided no evidence of changes in DA plasma concentrations with chronic exposure. DA exposure was not associated with reproductive toxicity or adverse changes in the physical characteristics of newborns. However, in an unanticipated finding, our clinical observations revealed the presence of subtle neurological effects in the form of intentional tremors in the exposed adult females. While females in both dose groups displayed increased tremoring, the effect was dose-dependent and observed at a higher rate in females exposed to 0.15 mg/kg/day. These results demonstrate that chronic, low-level exposure to DA is associated with injury to the adult CNS and suggest that current regulatory guidelines designed to protect human health may not be adequate for high-frequency shellfish consumers.
标题：天然存在的兴奋性毒素软骨藻酸（DA）在贝类和鱼类中生物积累，会引起胃肠道疾病，大量摄入可导致从烦躁不安到幻觉、记忆丧失、癫痫发作和昏迷等一系列症状。
摘要：由于产生 DA 的藻类大量繁殖，且对慢性低剂量暴露的危害知之甚少，我们在非人类灵长类动物模型中开展了一项针对 DA 的生殖和发育影响的临床前研究。为此，32 只成年雌性猕猴每日经口暴露于 0、0.075 或 0.15mg/kg/天的 DA，在怀孕前和怀孕期间进行。雌性与未暴露的雄性交配，对新生婴儿进行评估。该研究结果表明，慢性暴露不会改变 DA 的血浆浓度。DA 暴露与生殖毒性或新生儿身体特征的不良变化无关。然而，出乎意料的是，我们的临床观察发现，暴露的成年雌性出现了微妙的神经影响，表现为有意震颤。虽然两个剂量组的女性都出现了震颤增加，但这种影响呈剂量依赖性，在暴露于 0.15mg/kg/天的女性中更为明显。这些结果表明，慢性低水平暴露于 DA 会导致成年中枢神经系统受损，并表明旨在保护人类健康的当前监管指南可能不足以保护高频食用贝类的人群。
