Pharmaceuticals and microplastics constitute potential hazards in aquatic systems, but their combined effects and underlying toxicity mechanisms remain largely unknown. In this study, a simultaneous characterization of bioaccumulation, associated metabolomic alterations and potential recovery mechanisms was performed. Specifically, a bioassay on Mediterranean mussels (Mytilus galloprovincialis) was carried out with polyethylene microplastics (PE-MPLs, 1 mg/L) and citalopram or bezafibrate (500 ng/L). Single and co-exposure scenarios lasted 21 days, followed by a 7-day depuration period to assess their potential recovery. PE-MPLs delayed the bioaccumulation of citalopram (lower mean at 10 d: 447 compared to 770 ng/g dw under single exposure), although reaching similar tissue concentrations after 21 d. A more limited accumulation of bezafibrate was observed overall, regardless of PE-MPLs co-exposure (<MQL-3.2 ng/g dw). Metabolic profiles showed a strong effect of pharmaceuticals, generally independent of PE-MPLs co-exposure. Alterations of the citrate cycle (bezafibrate exposure) and steroid and prostaglandin metabolism (citalopram and bezafibrate exposures) were highlighted. PE-MPLs alone also impacted metabolic pathways, such as neurotransmitters or purine metabolism. After depuration, relevant latent or long-lasting effects were demonstrated as, for instance, the effect of citalopram on neurotransmitters metabolism. Altogether, the observed molecular-level responses to pharmaceuticals and/or PE-MPLs may lead to a dysregulation of mussels' reproduction, energy metabolism, and/or immunity.
Keywords: Antidepressant; Depuration; LC-HRMS; Lipid regulator; Mixture.
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