Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czech Republic.
Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, 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.
Sci Total Environ. 2022 Nov 25;849:157921. doi: 10.1016/j.scitotenv.2022.157921. Epub 2022 Aug 9.
One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs - diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100× higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.
非甾体抗炎药（NSAIDs）是造成地表水污染的主要因素之一，它们会污染食物链并影响非目标水生物种。由于目前很少有研究关注 NSAIDs 对淡水鱼类的毒性作用，特别是饮食暴露后的毒性作用，因此我们选择虹鳟（Oncorhynchus mykiss）作为理想模型，以研究两种 NSAIDs（双氯芬酸（DCF）和布洛芬（IBP））的影响。本研究的目的是测试这些药物在环境相关浓度下的毒性，同时还包括暴露剂量高 100 倍的药物混合物，并深入了解这些药物的毒性作用机制。研究结果表明，肾脏是受影响最严重的器官，玻璃样变性、氧化应激标志物增加以及热休克蛋白 70 的基因表达变化均表明肾脏毒性。此外，通过组织病理学分析（即萎缩、充血和炎症细胞增加）、生化标志物变化、热休克蛋白 70 mRNA 增加以及氧化应激分析，证实了肝脏毒性。鳃局部变形，并出现炎症过程和坏死区域的迹象。鉴于氧化应激标志物和热休克蛋白 70 mRNA 的增加，氧运输的严重受损可能是 NSAIDs 的毒性途径之一。关于微生物组，检测到革兰氏阳性菌过度生长；特别是，梭菌/厚壁菌比值的显著失调。总之，饮食暴露于 NSAIDs 后观察到的变化会影响生物体的稳态，诱导 ROS 产生，加剧炎症并导致肠道微生物失调。即使是环境相关浓度的 NSAIDs 也会对水生生态系统构成风险，因为它改变了虹鳟的健康参数，我们假设 NSAIDs 的毒性作用发生在线粒体和蛋白质水平。
