Linking physiological mechanisms and the chronic impacts of bioaccumulated metals in aquatic organisms

这项研究计划从最初的动态平衡破坏到最终的驯化，研究了彩虹鲑慢性亚致死性镍和铜中毒的生理机制。随着金属从水中吸收到不同的组织(鳃、肝脏、肾脏、肌肉)，随着组织中金属浓度的增加，研究将跟踪发生的生理破坏，并区分可以解毒和储存(或消除)金属的细胞防御系统和与累积的金属反应并受到破坏的细胞元素。一种将生物积累的金属划分为代表潜在有毒金属形式和解毒形式的不同细胞池的方法将与生理反应联系在一起。将评估一系列生理反应(例如，免疫功能、应激反应、维生素A代谢、呼吸功能、离子调节和活性氧物种(ROS)的产生)。据假设，主要的破坏将发生在离子稳态和产生活性氧物种(ROS)，这些将在暴露期间以两相方式发生，首先是离子稳态，然后是ROS。根据这一假设，暴露早期对金属的摄取预计会扰乱离子调节(铜与钠干扰，镍与镁干扰)。这是因为来自对急性金属暴露的生理效应的研究数据显示了对离子调节的影响。在暴露的第二阶段，大量金属将渗透到细胞中，随着浓度的增加，解毒机制将不堪重负，将产生ROS。在这种情况下的预测是，ROS诱导的病理生理学将直接与毒物池中金属亚细胞分数的增加有关。预期镍和铜在离子调节和组织生物积累方面表现出相反的结果，但在细胞分配和ROS的产生方面具有相似之处。这些研究旨在了解鱼类适应金属暴露时的生理反应、损伤修复和调整；这些数据将对更好地管理金属对环境的影响具有社会经济意义。

This research program addresses the physiological mechanisms of chronic sublethal Ni and Cu toxicity in rainbow trout, from initial disruption of homeostasis to final acclimation. Investigations will follow the physiological disruption that occurs as metals are taken up from the water into various tissues (gills, liver, kidney, muscle) and, as the concentration of metal in tissues increases, distinguish between cellular defense systems that can detoxify and store (or eliminate) the metal and cellular elements that react with and are damaged by accumulated metal. A method of partitioning bioaccumulated metal into distinct cellular pools representing potentially toxic forms of metal and detoxified forms will be linked to physiological responses. A suite of physiological responses will be assessed (e.g. immune function, stress response, vitamin A metabolism, respiratory function, ion regulation and generation of reactive oxygen species (ROS)). It is hypothesized that the primary disruptions will be in ion homeostasis and in the generation of reactive oxygen species (ROS) and that these will occur in a biphasic manner during exposure, first ion homeostasis then ROS. Under this hypothesis, the uptake of metal early in the exposure is expected to disrupt ion regulation (Cu interfering with Na and Ni with Mg). This is predicted because data from studies on the physiological effects of acute metal exposure show impacts on ion regulation. In the second phase of the exposure significant amounts of metal will have permeated into cells and as concentrations rise, detoxification mechanisms will be overwhelmed and ROS will be generated. The prediction in this case is that ROS induced pathophysiology will be directly related to increases in the subcellular fraction of metal in the toxic pool. Ni and Cu are expected to show contrasting results related to ion regulation and tissue bioaccumulation but similarities in the cellular partitioning and generation of ROS. The studies are designed to understand the physiological responses, damage repair and adjustments in fish as they acclimate to metal exposure; the data will be of socio-economic relevance to better manage the impacts of metals in the environment.