Integrated Toxicology and Environmental Health Program, Nicholas School of the Environment, Duke University, Durham, NC 27708, USA.
Aquat Toxicol. 2019 Nov;216:105298. doi: 10.1016/j.aquatox.2019.105298. Epub 2019 Sep 13.
Organisms are routinely subjected to a variety of environmental and chemical perturbations simultaneously. Often, multi-stressor exposures result in unpredictable toxicity that occurs through unidentified mechanisms. Here, we focus on polycyclic aromatic hydrocarbons (PAHs) and hypoxia, two environmental and physiological stressors that are known to co-occur in the environment. The aim of this study was to assess whether interactive mitochondrial dysfunction resulted from co-exposures of PAHs and hypoxia. Zebrafish embryos were co-exposed to non-teratogenic concentrations of an environmental PAH mixture and hypoxia beginning at 6 hpf for an acute period of 24 h and afterwards were given either no recovery period, 45 min, 5 -hs, or 18 -hs of recovery time in clean conditions. Mitochondrial function and integrity were assessed through the use of both in ovo and in vitro assays. Hypoxia exposures resulted in drastic reductions in parameters relating to mitochondrial respiration, ATP turnover, and mitochondrial DNA integrity. PAH exposures affected ATP production and content, as well as mitochondrial membrane dynamics and lactate content. While PAH and hypoxia exposures caused a broad range of effects, there appeared to be very little interaction between the two stressors in the co-exposure group. However, because hypoxia significantly altered mitochondrial function, the possibility remains that these effects may limit an individual's ability to respond to PAH toxicity and therefore could cause downstream interactive effects.
生物体经常同时受到多种环境和化学因素的干扰。通常,多胁迫暴露会导致无法预测的毒性,其发生机制尚不清楚。在这里,我们关注多环芳烃 (PAHs) 和缺氧,这两种环境和生理胁迫因素已知在环境中同时存在。本研究的目的是评估 PAHs 和缺氧的共暴露是否会导致相互作用的线粒体功能障碍。从 6 hpf 开始,将斑马鱼胚胎暴露于非致畸浓度的环境 PAH 混合物和缺氧中,进行 24 小时的急性暴露,然后在清洁条件下给予无恢复期、45 分钟、5 小时或 18 小时的恢复期。通过体内和体外测定来评估线粒体功能和完整性。缺氧暴露导致与线粒体呼吸、ATP 周转率和线粒体 DNA 完整性相关的参数急剧下降。PAH 暴露会影响 ATP 的产生和含量,以及线粒体膜动力学和乳酸含量。虽然 PAH 和缺氧暴露造成了广泛的影响,但在共暴露组中,两种胁迫因素之间似乎几乎没有相互作用。然而,由于缺氧显著改变了线粒体功能,因此仍然存在这些影响可能会限制个体对 PAH 毒性的反应能力,并可能导致下游的相互作用效应的可能性。