Mechanisms for cardiotoxicity-related mortality in fish

鱼类心脏毒性相关死亡的机制

• 批准号: 436219-2013
• 负责人: Gilmour, Robert
• 金额: $ 2.11万
• 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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=533477
• 关键词: Mechanisms; cardiotoxicity; 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) that 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, whereas 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-resistant 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 fishes.

环境灾难，如石油泄漏、工业废物进入流域和农药流失，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，这会减少心脏泵送的血液量，随着时间的推移会导致器官衰竭和死亡。 或者，可能发生心脏泵血完全停止。 因为心脏的收缩是由电事件（心脏动作电位）触发的，所以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，而动作电位的缺乏可能导致心跳停止。 以前使用胚胎或基因操纵的鱼心脏细胞的研究表明，环境毒素可能会导致不规则的跳动和停止跳动。 然而，这些影响发生的确切机制尚未确定，也没有证明成年鱼心脏细胞急性暴露于环境毒素后，这些影响，将在野外发生。 我们提出了一个系统的研究选定的环境毒素（二恶英，多溴联苯醚和原油成分，如多环芳烃）对青少年和成年斑马鱼心脏细胞的电活动的影响，以表征这些毒素对动作电位的特性和个人的离子电流的特性，动作电位的产生的基础上的影响。 毒素诱导的心脏毒性作用的离子机制的识别可能会导致新的策略，以保护鱼类免受环境毒素，也许通过遗传工程鱼，使他们携带毒素的离子电流通常针对的毒素抗性变体。 这种战略可以减少环境灾难对渔业的经济影响，并保护濒危或其他重要的鱼类物种。