Department of Environmental Toxicology, Swiss Federal Institute of Aquatic Science and Technology, Eawag, 8600 Dübendorf, Switzerland.
Department of Environmental Chemistry, Swiss Federal Institute of Aquatic Science and Technology, Eawag, 8600 Dübendorf, Switzerland; Department of Environmental Systems Science, ETH Zürich, 8092 Zürich, Switzerland.
Sci Total Environ. 2024 May 15;925:171769. doi: 10.1016/j.scitotenv.2024.171769. Epub 2024 Mar 17.
Aquatic ecosystems continue to be threatened by chemical pollution. To what extent organisms are able to cope with chemical exposure depends on their ability to display mechanisms of defense across different organs. Among these mechanisms, biotransformation processes represent key physiological responses that facilitate detoxification and reduce the bioaccumulation potential of chemicals. Biotransformation does not only depend on the ability of different organs to display biotransformation enzymes but also on the affinity of chemicals towards these enzymes. In the present study, we explored the ability of different organs and of two freshwater fish to support biotransformation processes through the determination of in vitro phase I and II biotransformation enzyme activity, and their role in supporting intrinsic clearance and the formation of biotransformation products. Three environmentally relevant pollutants were evaluated: the polycyclic aromatic hydrocarbon (PAH) pyrene (as recommended by the OECD 319b test guideline), the fungicide azoxystrobin, and the pharmaceutical propranolol. Comparative studies using S9 sub-cellular fractions derived from the liver, intestine, gills, and brain of brown trout (Salmo trutta) and rainbow trout (Oncorhynchus mykiss) revealed significant phase I and II enzyme activity in all organs. However, organ- and species-specific differences were found. In brown trout, significant extrahepatic biotransformation was observed for pyrene but not for azoxystrobin and propranolol. In rainbow trout, the brain appeared to biotransform azoxystrobin. In this same species, propranolol appeared to be biotransformed by the intestine and gills. Biotransformation products could be detected only from hepatic biotransformation, and their profiles and formation rates displayed species-specific patterns and occurred at different magnitudes. Altogether, our findings further contribute to the current understanding of organ-specific biotransformation capacity, beyond the expression and activity of enzymes, and its dependence on specific enzyme-chemical interactions to support mechanisms of defense against exposure.
水生生态系统继续受到化学污染的威胁。生物体在多大程度上能够应对化学暴露取决于它们在不同器官中显示防御机制的能力。在这些机制中,生物转化过程代表了促进解毒和降低化学物质生物累积潜力的关键生理反应。生物转化不仅取决于不同器官显示生物转化酶的能力,还取决于化学物质对这些酶的亲和力。在本研究中,我们通过测定体外第一相和第二相生物转化酶活性及其在支持内在清除率和生物转化产物形成中的作用,探索了不同器官和两种淡水鱼支持生物转化过程的能力。评估了三种与环境有关的污染物:多环芳烃(PAH)芘(如 OECD 319b 测试指南所推荐)、杀菌剂唑菌胺酯和药物普萘洛尔。使用来自褐鳟(Salmo trutta)和虹鳟(Oncorhynchus mykiss)肝脏、肠道、鳃和大脑的 S9 亚细胞级分进行的比较研究表明,所有器官均具有显著的第一相和第二相酶活性。然而,发现了器官和物种特异性差异。在褐鳟中,观察到芘的显著肝外生物转化,但唑菌胺酯和普萘洛尔没有。在虹鳟中,大脑似乎可以转化唑菌胺酯。在同一物种中,肠和鳃似乎可以转化普萘洛尔。仅从肝生物转化中可以检测到生物转化产物,其谱和形成速率显示出物种特异性模式,并且发生的幅度不同。总之,我们的研究结果进一步加深了对器官特异性生物转化能力的理解,超越了酶的表达和活性,以及其对支持防御机制对抗暴露的特定酶-化学相互作用的依赖。