Mezzelani M, Gorbi S, Fattorini D, d'Errico G, Benedetti M, Milan M, Bargelloni L, Regoli F
Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
Dipartimento di Biomedicina Comparata e Alimentazione (BCA), Università di Padova, Italy.
Aquat Toxicol. 2016 Nov;180:306-319. doi: 10.1016/j.aquatox.2016.10.006. Epub 2016 Oct 11.
The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses. Results indicated the capability of mussels to accumulate DIC and NIM, while AMP, IBU and KET were always below detection limit. A large panel of ecotoxicological biomarkers revealed the early onset of alterations induced by tested NSAIDs on immunological responses, lipid metabolism and DNA integrity. The gene transcription analysis through DNA microarrays, supported cellular biomarker results, with clear modulation of a large number of genes involved in the arachidonic acid and lipid metabolism, immune responses, cell cycle and DNA repair. The overall results indicated an ecotoxicological concern for pharmaceuticals in M. galloprovincialis, with transcriptional responses appearing as sensitive exposure biomarkers at low levels of exposure: such changes, however, are not always paralleled by corresponding functional effects, suggesting caution when interpreting observed effects in terms of perturbed cellular pathways. Fascinating similarities can also be proposed in the mode of action of NSAIDs between bivalves and vertebrate species.
本研究的目的是提供新的见解，以了解贻贝（Mytilus galloprovincialis）暴露于环境实际浓度（0.5μg/L）的对乙酰氨基酚（AMP）、双氯芬酸（DIC）、布洛芬（IBU）、酮洛芬（KET）或尼美舒利（NIM）等各种非甾体抗炎药（NSAIDs）时的积累情况及其可能的不利影响。对贻贝组织中药物的测量与细胞水平的功能改变和转录组反应相结合。结果表明贻贝有积累双氯芬酸和尼美舒利的能力，而对乙酰氨基酚、布洛芬和酮洛芬始终低于检测限。大量的生态毒理学生物标志物显示，受试非甾体抗炎药对免疫反应、脂质代谢和DNA完整性诱导的改变较早出现。通过DNA微阵列进行的基因转录分析支持了细胞生物标志物的结果，大量参与花生四烯酸和脂质代谢、免疫反应、细胞周期和DNA修复的基因有明显的调控。总体结果表明，贻贝中的药物存在生态毒理学问题，转录反应在低暴露水平下表现为敏感的暴露生物标志物：然而，这些变化并不总是与相应的功能效应平行，这表明在根据细胞途径紊乱来解释观察到的效应时要谨慎。双壳贝类和脊椎动物物种之间在非甾体抗炎药的作用方式上也可以提出引人入胜的相似之处。
