Sex steroids and metabolic responses in mussels Mytilus galloprovincialis exposed to drospirenone

• Published in: Ecotoxicology and environmental safety 2017-09, Vol.143, p.166-172
• Main Authors: Cappello, Tiziana, Fernandes, Denise, Maisano, Maria, Casano, Andrea, Bonastre, Marta, Bebianno, Maria João, Mauceri, Angela, Fasulo, Salvatore, Porte, Cinta
• Format: Article
• Language: English
• Subjects: Androstenes - toxicity; Animals; Digestive gland; Drospirenone; Female; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - metabolism; Gonads - drug effects; Gonads - metabolism; Male; Metabolomics; Mussels; Mytilus - drug effects; Mytilus - metabolism; NMR-based metabolomics; Progesterone; Progesterone - metabolism; Progestins; Testosterone - metabolism; Water Pollutants, Chemical - toxicity
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2017.05.031

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 (1H NMR)-based metabolomics approach enabled a comprehensive assessment of DRO effects in mussels. Specifically, 1H 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. •Biological effects of different doses of drospirenone were assessed in mussels.•No significant effects were observed on gonad maturation and sex steroid levels.•Disorders in energy, amino acids, and glycerophospholipid metabolism were observed.•Metabolomics is an effective tool in environmental risk assessment of pharmaceuticals.