Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, via Brecce Bianche (60131), Ancona, Italy.
Dipartimento di Biomedicina Comparata e Alimentazione, Università di Padova, Viale dell'Università, 16, 35020 Legnaro (PD), Polo di Agripolis, Italy.
Environ Int. 2021 Jan;146:106269. doi: 10.1016/j.envint.2020.106269. Epub 2020 Nov 25.
Contaminants of emerging concern and ocean changes are key environmental stressors for marine species with possibly synergistic, but still unexplored, deleterious effects. In the present study the influence of a simulated ocean acidification scenario (pH = 7.6) was investigated on metabolism and sub-lethal effects of carbamazepine, CBZ (1 µg/L), chosen as one of the most widely diffused pharmaceuticals in marine organisms. A multidisciplinary approach was applied on mussels, M. galloprovincialis, integrating measurement of drug bioaccumulation with changes in the whole transcriptome, responsiveness of various biochemical and cellular biomarkers including immunological parameters, lipid and oxidative metabolism, onset of genotoxic effects. Chemical analyses revealed a limited influence of hypercapnia on accumulation and excretion of CBZ, while a complex network of biological responses was observed in gene expression profile and functional changes at cellular level. The modulation of gamma-aminobutyric acid (GABA) pathway suggested similarities with the Mechanism of Action known for vertebrates: immune responses, cellular homeostasis and oxidative system represented the processes targeted by combined stressors. The overall elaboration of results through a quantitative Weight of Evidence model, revealed clearly increased cellular hazard due to interactions of CBZ with acidification compared to single stressors.
新兴关注污染物和海洋变化是海洋物种的主要环境胁迫因素，它们可能具有协同作用，但仍具有潜在的有害影响。在本研究中，模拟了海洋酸化情景（pH = 7.6）对卡马西平（CBZ）（1μg/L）的代谢和亚致死效应的影响，选择卡马西平作为海洋生物中最广泛传播的药物之一。采用多学科方法研究贻贝（M. galloprovincialis），将药物生物蓄积与整个转录组的变化、各种生化和细胞生物标志物（包括免疫参数）的反应性、脂质和氧化代谢、遗传毒性效应的发生相结合。化学分析表明，高二氧化碳对 CBZ 的积累和排泄影响有限，而在基因表达谱和细胞水平的功能变化中观察到复杂的生物学反应网络。γ-氨基丁酸（GABA）途径的调节表明与脊椎动物的作用机制相似：免疫反应、细胞内稳态和氧化系统是联合胁迫作用的靶点。通过定量证据权重模型全面阐述结果，清楚地表明由于 CBZ 与酸化的相互作用，导致细胞危害明显增加，与单一胁迫因素相比。
