Integrative oxidative stress biomarkers in gills and digestive gland of the combined exposure to citalopram and bezafibrate with polyethylene microplastics on mussels Mytilus galloprovincialis☆

Pharmaceutical active compounds (PhACs) and microplastics (MPs) have been detected in different marine compartments from coastal areas, raising concerns due to their simultaneous discharge through wastewater treatment plants (WWTPs) and the role of MPs as vectors of pollutants for marine organisms. This study investigates the biochemical effects of citalopram (CIT) and bezafibrate (BEZ) on the mussel Mytilus galloprovincialis, at environmentally relevant concentrations, and their co- exposure with high-density polyethylene (HDPE) MPs. MPs accumulated in gills and digestive glands during exposure, but they were rapidly eliminated after depuration, except for a small fraction of the smallest MPs in gills. This study evaluated the biological effects in gills and digestive gland, and confirmed CIT induced oxidative stress in both tissues, exacerbated by the presence of MPs. BEZ, despite not being detected at high concentrations in the mussel tissues, activated an antioxidant response in gills and increasing the transcription of the genes Se-gpx and gst-pi in digestive gland. Both PhACs impaired the cholinergic pathway longterm, even after the depuration period, as indicated by decreased AChE levels in the gills, suggesting potential neurotoxic effects after prolonged exposure. Consequently, adverse effects were provoked by both PhACs with (CIT) and without (BEZ) significant bioaccumulation capacity.