Department of Animal Protection and Welfare & Veterinary Public Health, Faculty of Veterinary Hygiene and Ecology, University of Veterinary Sciences Brno, Czech Republic; Department of Zoology, Fisheries, Hydrobiology and Apiculture, Faculty of Agrisciences, Mendel University in Brno, Brno, Czech Republic; Department of Animal Breeding, Animal Nutrition and Biochemistry, Faculty of Veterinary Hygiene and Ecology, University of Veterinary Sciences Brno, Czech Republic.
Department of Animal Protection and Welfare & Veterinary Public Health, Faculty of Veterinary Hygiene and Ecology, University of Veterinary Sciences Brno, Czech Republic; Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czech Republic.
Sci Total Environ. 2023 Dec 15;904:166378. doi: 10.1016/j.scitotenv.2023.166378. Epub 2023 Aug 16.
The incidence of diseases of affluence, such as diabetes mellitus, cardiovascular diseases, high blood pressure, and high cholesterol has been reported to rise. Consequently, the concentrations of residues of drugs designed to treat these diseases have been rising in water bodies. Moreover, the toxicity of these pharmaceuticals towards fish and other non-target organisms can be even enhanced by microplastic particles that are reportedly present in surface water. Therefore, the aim of this study was to describe the effects of three highly prescribed drugs, in particular metoprolol, enalapril, and metformin on fish early-life stages. Also, it was hypothesized that polystyrene microparticles will increase the toxicity of metoprolol to fish early-life stages. Embryonal acute toxicity tests on Danio rerio and Cyprinus carpio were carried out in order to describe the possible toxic effects of metoprolol, enalapril, and metformin. Also, the acute toxicity of polystyrene microparticles and the combination of metoprolol with polystyrene microparticles were tested on D. rerio embryos. Additionally, a 31-day long embryo-larval subchronic toxicity test was carried out with C. carpio in order to describe the long-term effects of low concentrations of metoprolol. The results of the study show that both metoprolol and enalapril have the potential to disrupt the early development of the heart in the embryonal stages of fish. Also, enalapril and metformin together with polystyrene microparticles seem to possibly disrupt the reproduction cycle and act as endocrine disruptors. Both pure polystyrene microparticles and the combination of them with metoprolol affect inflammatory processes in organisms. Additionally, metformin alters several metabolism pathways in fish early-life stages. The results of the study bring new evidence that even low, environmentally-relevant concentrations of pharmaceuticals have the potential to disrupt the early development of fish, particularly on a molecular level.
富贵病（如糖尿病、心血管疾病、高血压和高胆固醇）的发病率据报道呈上升趋势。因此，用于治疗这些疾病的药物残留浓度在水体中不断上升。此外，据报道，存在于地表水的微塑料颗粒会增强这些药物对鱼类和其他非靶标生物的毒性。因此，本研究的目的是描述三种高度规定药物（特别是美托洛尔、依那普利和二甲双胍）对鱼类早期生命阶段的影响。此外，还假设聚苯乙烯微球将增加美托洛尔对鱼类早期生命阶段的毒性。对斑马鱼和鲤鱼进行胚胎急性毒性试验，以描述美托洛尔、依那普利和二甲双胍可能产生的毒性作用。此外，还对聚苯乙烯微球和聚苯乙烯微球与美托洛尔的混合物对斑马鱼胚胎的急性毒性进行了测试。此外，还进行了为期 31 天的鲤鱼胚胎-幼鱼亚慢性毒性试验，以描述低浓度美托洛尔的长期影响。研究结果表明，美托洛尔和依那普利都有可能破坏鱼类胚胎期心脏的早期发育。此外，依那普利和二甲双胍与聚苯乙烯微球一起似乎可能破坏生殖周期并充当内分泌干扰物。纯聚苯乙烯微球以及它们与美托洛尔的混合物都会影响生物体的炎症过程。此外，二甲双胍改变了鱼类早期生命阶段的几种代谢途径。该研究结果提供了新的证据，表明即使是环境相关的低浓度药物也有可能破坏鱼类的早期发育，尤其是在分子水平上。
