Department of Biology, Norwegian University of Science and Technology (NTNU), Norway; Department of Veterinary Science, University of Pisa, San Piero a Grado (PI), 56122, Italy; Laboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, United States.
Department of Veterinary Science, University of Pisa, San Piero a Grado (PI), 56122, Italy; Interuniversity Center of Marine Biology (CIBM) "G. Bacci", Leghorn, 57128, Italy.
Aquat Toxicol. 2020 Dec;229:105677. doi: 10.1016/j.aquatox.2020.105677. Epub 2020 Nov 5.
Racemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are widely used non-steroidal anti-inflammatory drugs (NSAIDs), and commonly detected in the aquatic environment. The present study has evaluated the toxicological effects of RS-KP and S(+)-KP on biotransformation and oxidative stress responses in gills and liver of Atlantic salmon. Fish were exposed for 10 days using different concentrations of RS-KP (1, 10 and 100 μg/L) and S(+)-KP (0.5, 5 and 50 μg/L). Biotransformation and oxidative stress responses were analysed at both transcript and functional levels. In the gills, significant inhibitory effect at transcriptional and enzymatic levels were observed for biotransformation and oxidative stress responses. On the contrary, biotransformation responses were significantly increased at transcriptional and translational levels in the liver, while the associated enzymatic activities did not parallel this trend and were inhibited and further demonstrated by principal component analysis (PCA). Our findings showed that both compounds produced comparable toxicological effects, by producing organ-specific effect differences. RS-KP and S(+)-KP did not bioaccumulate in fish muscle, either due to rapid metabolism or excretion as a result of their hydrophobic properties. Interestingly, the inhibitory effects observed in the gills suggest that these drugs may not undergo first pass metabolism, that might result to downstream differences in toxicological outcomes.
消旋酮洛芬（RS-KP）及其对映体右旋酮洛芬（S(+)-KP）是广泛使用的非甾体抗炎药（NSAIDs），并且通常在水环境中被检测到。本研究评估了 RS-KP 和 S(+)-KP 对大西洋鲑鱼鳃和肝脏生物转化和氧化应激反应的毒理学影响。鱼在不同浓度的 RS-KP（1、10 和 100μg/L）和 S(+)-KP（0.5、5 和 50μg/L）中暴露 10 天。在转录和功能水平上分析了生物转化和氧化应激反应。在鳃中，观察到生物转化和氧化应激反应的转录和酶水平上的显著抑制作用。相反，在肝脏中，生物转化反应在转录和翻译水平上显著增加，而相关的酶活性并没有平行这种趋势，并通过主成分分析（PCA）进一步证明。我们的研究结果表明，这两种化合物产生了类似的毒理学效应，产生了器官特异性的效应差异。RS-KP 和 S(+)-KP 并没有在鱼肌肉中生物积累，这可能是由于它们的疏水性导致快速代谢或排泄。有趣的是，在鳃中观察到的抑制作用表明，这些药物可能不会经历首过代谢，这可能导致下游毒理学结果的差异。
