Instituto de Ciencias Marinas de Andalucía, Consejo Superior de Investigaciones Científicas, Polígono Río San Pedro s/n, 11510 Puerto Real (Cádiz), Spain.
Environ Toxicol Pharmacol. 2009 Sep;28(2):237-42. doi: 10.1016/j.etap.2009.04.009. Epub 2009 Apr 24.
A biomarker approach was undertaken using the mussel Elliptio complanata to assess the ecotoxicological effects after injection of a range concentration (0-10mM) of three different PPCPs: carbamazepine, caffeine, methotrexate; and an effluent extract (C8) from St. Lawrence wastewaters treatment plant (Montreal, Canada). A battery of biomarkers, involving oxidative stress and genotoxicity responses: glutation-S-transferase (GST), ethoxyresorufin O-deethylase (EROD), dibenzylflourescein dealkylase (DBF), xanthine oxidoreductase (XOR) activities, lipid peroxidation (LPO) and DNA damage were determined in gonad and digestive gland tissues after 48 h of injection. Results showed an induction of the oxidative metabolism with increasing pharmaceutical concentration in those mussels injected with the PPCPs and the effluent extract. Phase I detoxification enzymes were significantly induced (p<0.05), concretely DBF activity was significantly induced after caffeine, carbamazipine and C8 injection; and EROD activity after C8 and methotrexate injection. Oxidative stress induction only lead to lipid peroxidation (p<0.05) in organisms injected with carbamazepine and caffeine and DNA damage in organisms injected with methotrexate (p<0.05). EROD and DBF enzymatic activities have been found to be suitable biomarkers to determine bioavailability of pharmaceuticals. LPO and DNA damage to determine possible associated adverse effects. Nevertheless, their validation in realistic exposure scenarios and under exposure conditions should be performed in future research.
采用贻贝（Elliptio complanata）作为生物标志物方法，评估了注射三种不同 PPCPs（卡马西平、咖啡因、甲氨蝶呤）和圣劳伦斯废水处理厂（加拿大蒙特利尔）流出物提取物（C8）的一系列浓度（0-10mM）后的生态毒理学效应。一组生物标志物，包括氧化应激和遗传毒性反应：谷胱甘肽-S-转移酶（GST）、乙氧基-resorufin O-脱乙基酶（EROD）、二苄基荧光素脱烷基酶（DBF）、黄嘌呤氧化还原酶（XOR）活性、脂质过氧化（LPO）和 DNA 损伤，在注射后 48 小时在性腺和消化腺组织中进行了测定。结果表明，随着注射 PPCPs 和流出物提取物的药物浓度的增加，氧化代谢受到诱导。I 相解毒酶明显诱导（p<0.05），具体表现为咖啡因、卡马西平和 C8 注射后 DBF 活性明显诱导；C8 和甲氨蝶呤注射后 EROD 活性明显诱导。氧化应激诱导仅导致注射卡马西平和咖啡因的生物体中的脂质过氧化（p<0.05）和注射甲氨蝶呤的生物体中的 DNA 损伤（p<0.05）。已经发现 EROD 和 DBF 酶活性是确定药物生物利用度的合适生物标志物。LPO 和 DNA 损伤可确定可能相关的不良反应。然而，在未来的研究中，应在现实暴露场景和暴露条件下对其进行验证。
