Mechanisms of cardiotoxicty-related mortality in fish

鱼类心脏毒性相关死亡的机制

• 批准号: RGPIN-2014-04117
• 负责人: Gilmour, Robert
• 金额: $ 2.19万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587612
• 关键词: Mechanisms; cardiotoxicty; related; mortality; fish

Environmental catastrophes such as oil spills, introduction of industrial waste into watersheds and pesticide run-offs often are associated with fish kills. The cause of death under these circumstances is still uncertain, but it may relate to a rapid, irregular heartbeat (palpitations), which reduces the amount of blood pumped by the heart, which over time can cause organ failure and death. Alternatively, complete cessation of heart pumping may occur. Because contraction of the heart is triggered by an electrical event, the cardiac action potential, abnormalities in the generation of action potentials may underlie the irregular heartbeats that cause death and an absence of action potentials may cause cessation of beating. Previous studies using embryonic or genetically manipulated fish heart cells have suggested that environmental toxins may cause both irregular beating and the cessation of beating. However, the exact mechanisms by which these effects occur have not been defined, nor have these effects been demonstrated following acute exposure of adult fish heart cells to environment toxins, as would occur in the wild. We propose a systematic study of the effects of selected environmental toxins (dioxins, polybrominated diphenyl ethers and crude oil constituents such as polycyclic aromatic hydrocarbons) on the electrical activity of juvenile and adult zebrafish heart cells to characterize the effects of these toxins on action potential characteristics and on the properties of the individual ionic currents that underlie the generation of action potentials. Identification of the ionic mechanisms for toxin-induced cardiotoxic effects could lead to new strategies to protect fish from environment toxins, perhaps by genetically engineering fish so that they carry a toxin-immune variant of the ionic current normally targeted by the toxin. Such a strategy could reduce the economic impact of environmental catastrophes on the fishing industry and offer protection of endangered or otherwise important species of fish.

环境灾难，如石油泄漏、工业废物进入流域和农药径流，往往与鱼类死亡有关。在这种情况下死亡的原因仍然不确定，但它可能与快速、不规则的心跳（心悸）有关，这减少了心脏泵出的血液量，随着时间的推移可能导致器官衰竭和死亡。或者，完全停止心脏跳动也可能发生。由于心脏收缩是由一个电事件，即心脏动作电位触发的，动作电位产生的异常可能是导致死亡的不规则心跳的基础，而动作电位的缺失可能导致停止跳动。先前使用胚胎或基因操纵的鱼心脏细胞的研究表明，环境毒素可能导致不规则跳动和停止跳动。然而，这些影响发生的确切机制尚未确定，也没有在成年鱼心脏细胞急性暴露于环境毒素后证明这些影响，就像在野外发生的那样。我们建议对选定的环境毒素（二恶英、多溴联苯醚和原油成分如多环芳烃）对幼鱼和成年斑马鱼心脏细胞电活动的影响进行系统研究，以表征这些毒素对动作电位特征的影响，以及对产生动作电位的单个离子电流特性的影响。确定毒素诱导的心脏毒性作用的离子机制可能会导致保护鱼类免受环境毒素侵害的新策略，也许可以通过基因工程使鱼类携带毒素通常靶向的离子电流的毒素免疫变体。这种战略可以减少环境灾难对渔业的经济影响，并保护濒临灭绝或其他重要的鱼类品种。