CIMA, Marine and Environmental Research Centre, University of Algarve, Faro, Campus de Gambelas, 8000-135 Faro, Portugal.
CIMA, Marine and Environmental Research Centre, University of Algarve, Faro, Campus de Gambelas, 8000-135 Faro, Portugal.
Aquat Toxicol. 2014 Mar;148:221-30. doi: 10.1016/j.aquatox.2014.01.011. Epub 2014 Jan 21.
In recent years, research studies have increasingly focused on assessing the occurrence of active pharmaceutical ingredients (APIs) in ecosystems. However, much remains unknown concerning the potential effects on APIs on non-target organisms due to the complexity of the mode of action, reactivity and bioconcentration potential for each specific drug. The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is one of the most frequently detected APIs in surface waters worldwide and has recently been included in the list of priority substances under the European Commission. In this study, mussels (Mytilus galloprovincialis) were exposed to an environmentally relevant nominal concentration of DCF (250 ng L(-1)) over 15 days. The responses of several biomarkers were assessed in the mussel tissues: condition index (CI); superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and phase II glutathione-S-transferase (GST) activities, lipid peroxidation levels (LPO) associated with oxidative stress, acetylcholinesterase (AChE) activity related to neurotoxic effects and vitellogenin-like proteins linked to endocrine disruption. This study demonstrated significant induction of SOD and GR activities in the gills in addition to high CAT activity and LPO levels in the digestive gland. Phase II GST remained unaltered in both tissues, while the up-regulation of the AChE activity was directly related to the vitellogenin-like protein levels in exposed females, indicating an alteration in the estrogenic activity, rather than a breakdown in cholinergic neurotransmission function. This study confirmed that DCF at a concentration often observed in surface water induces tissue-specific biomarker responses. Finally, this study also revealed the importance of a multi-biomarker approach when assessing the potentially deleterious effects in a species that may be vulnerable to the continuously discharge of APIs into the ecosystems; this approach provides crucial new information regarding the unknown effects of DCF.
近年来,研究越来越关注评估生态系统中活性药物成分(APIs)的发生情况。然而,由于每种特定药物作用模式、反应性和生物浓缩潜力的复杂性,对于 API 对非目标生物的潜在影响,我们仍知之甚少。非甾体抗炎药(NSAID)双氯芬酸(DCF)是世界范围内地表水中最常检测到的 API 之一,最近已被列入欧盟委员会优先物质清单。在这项研究中,贻贝(Mytilus galloprovincialis)在 15 天内暴露于环境相关的 DCF 名义浓度(250ng/L)下。评估了贻贝组织中几种生物标志物的反应:状况指数(CI);超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)和 II 相谷胱甘肽-S-转移酶(GST)活性、与氧化应激相关的脂质过氧化水平(LPO)、与神经毒性相关的乙酰胆碱酯酶(AChE)活性以及与内分泌干扰相关的卵黄蛋白原样蛋白。这项研究表明,SOD 和 GR 活性在鳃中显著诱导,同时 CAT 活性和消化腺中的 LPO 水平升高。II 相 GST 在两种组织中均保持不变,而 AChE 活性的上调与暴露雌性的卵黄蛋白原样蛋白水平直接相关,表明雌激素活性的改变,而不是胆碱能神经传递功能的破坏。这项研究证实,在地表水中经常观察到的浓度下,DCF 会诱导组织特异性生物标志物反应。最后,这项研究还揭示了在评估可能易受 API 持续排放到生态系统中的物种的潜在有害影响时,多生物标志物方法的重要性;这种方法提供了有关 DCF 未知影响的关键新信息。