Cappello Tiziana, Fernandes Denise, Maisano Maria, Casano Andrea, Bonastre Marta, Bebianno Maria João, Mauceri Angela, Fasulo Salvatore, Porte Cinta
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Spain.
Ecotoxicol Environ Saf. 2017 Sep;143:166-172. doi: 10.1016/j.ecoenv.2017.05.031. Epub 2017 May 23.
Drospirenone (DRO) is a synthetic progestin derived from 17α-spironolactone with a pharmacological mechanism of action similar to progesterone. Despite its wide use as pharmaceutical and consequent continuous release into the aquatic environment, DRO effects have been poorly investigated on aquatic biota. In order to unravel the toxicity mechanisms of DRO, mussels Mytilus galloprovincialis were exposed for 7 days to different concentrations of DRO, namely 20ng/L (Low; L), 200ng/L (Medium; M), 2000ng/L (High; H) and 10μg/L (Super High; SH) nominal doses. Following exposure, no significant effect was observed on gonad maturation of treated and untreated mussels. The levels of progesterone (P4) and testosterone (T) were measured in mantle/gonad tissues and no significant alteration detected after exposure. However, the application of a protonic nuclear magnetic resonance (H NMR)-based metabolomics approach enabled a comprehensive assessment of DRO effects in mussels. Specifically, H NMR metabolic fingerprints of digestive glands of DRO treated mussel groups were clearly separated from each other and from controls through a principal component analysis (PCA). Moreover, a number of metabolites involved in different metabolic pathways were found to significantly change in DRO-exposed mussels compared to control, suggesting the occurrence of alterations in energy metabolism, amino acids metabolism, and glycerophospholipid metabolism. Overall, despite no changes in gonad maturation and steroids levels were recorded in mussels after DRO exposure, the metabolomics approach demonstrated its effectiveness and high sensitivity in elucidating DRO-induced metabolic disturbances in marine mussels, and thus its usefulness in the environmental risk assessment of pharmaceuticals.
屈螺酮（DRO）是一种从17α-螺内酯衍生而来的合成孕激素，其药理作用机制与孕酮相似。尽管DRO作为药物被广泛使用并因此持续释放到水生环境中，但对水生生物群的影响却鲜有研究。为了阐明DRO的毒性机制，将加利福尼亚贻贝暴露于不同浓度的DRO中7天，即名义剂量20纳克/升（低；L）、200纳克/升（中；M）、2000纳克/升（高；H）和10微克/升（超高；SH）。暴露后，未观察到处理组和未处理组贻贝性腺成熟有显著影响。测量了外套膜/性腺组织中孕酮（P4）和睾酮（T）的水平，暴露后未检测到显著变化。然而，基于质子核磁共振（H NMR）的代谢组学方法能够全面评估DRO对贻贝的影响。具体而言，通过主成分分析（PCA），DRO处理的贻贝组消化腺的H NMR代谢指纹彼此之间以及与对照组明显分离。此外，与对照组相比，发现DRO暴露的贻贝中有许多参与不同代谢途径的代谢物发生了显著变化，这表明能量代谢、氨基酸代谢和甘油磷脂代谢发生了改变。总体而言，尽管DRO暴露后贻贝的性腺成熟和类固醇水平没有变化，但代谢组学方法在阐明DRO诱导的海洋贻贝代谢紊乱方面显示出其有效性和高灵敏度，因此在药物环境风险评估中具有实用性。
