Antidepressants and their metabolites primarily affect lysosomal functions in the marine mussel, Mytilus galloprovincialis

Ayesha Rafiq; Marco Capolupo; Giulia Addesse; Paola Valbonesi; Elena Fabbri

doi:10.1016/j.scitotenv.2023.166078

Antidepressants and their metabolites primarily affect lysosomal functions in the marine mussel, Mytilus galloprovincialis

Sci Total Environ. 2023 Dec 10:903:166078. doi: 10.1016/j.scitotenv.2023.166078. Epub 2023 Aug 11.

Authors

Ayesha Rafiq¹, Marco Capolupo², Giulia Addesse¹, Paola Valbonesi¹, Elena Fabbri³

Affiliations

¹ Department of Biological, Geological and Environmental Sciences, University of Bologna Campus of Ravenna, via S. Alberto 163, 48123 Ravenna, Italy.
² Italian Institute for Environmental Protection and Research (ISPRA), Rome, Italy.
³ Department of Biological, Geological and Environmental Sciences, University of Bologna Campus of Ravenna, via S. Alberto 163, 48123 Ravenna, Italy; National Future Biodiversity Center (NFBC), Palermo, Italy. Electronic address: elena.fabbri@unibo.it.

PMID: 37574064
DOI: 10.1016/j.scitotenv.2023.166078

Abstract

Antidepressants widely occur as emerging contaminants in marine coastal waters, with concentrations reported in the low ng/L range. Although at relatively lower levels with respect to other pharmaceuticals, antidepressants - fluoxetine (FLX) in particular - have attracted attention because of their striking effects exerted at low doses on marine invertebrates. In this study, the effects of four antidepressants including FLX, sertraline (SER), and citalopram, as members of the selective serotonin reuptake inhibitor (SSRI) class, and venlafaxine (VEN) as a member of the serotonin and norepinephrine reuptake inhibitor (SNRI) class, were evaluated in the mussel Mytilus galloprovincialis. In addition, the effects of two main metabolites of FLX and VEN, i.e., norfluoxetine (NFL) and O-desmethylvenlafaxine (ODV) respectively, were compared to those of the parent compounds. Eight concentrations of each drug (0.5-500 ng/L range) were tested on the early life stage endpoints of gamete fertilization and larval development at 48 h post fertilization (hpf). Egg fertilization was reduced by all compounds, except for VEN. Larval development at 48 hpf was affected by all SSRIs, but not by SNRIs. The above effects were significant but never exceeded 20 % of control values. Adult mussels were exposed in vivo for 7 days to environmental concentrations of the drugs (0.5, 5, and 10 ng/L) and a battery of eight biomarkers was assessed. Antidepressants primarily targeted lysosomal functions, decreasing haemocyte lysosome membrane stability (up to 70 % reduction) and increasing of the lysosome/cytosol ratio (up to 220 %), neutral lipid (up to 230 %), and lipofuscin (up to 440 %) accumulation in digestive gland. Only SER and NFL significantly affected catalase and glutathione-S-transferase activities in gills and digestive gland. NFL and ODV, were effective and sometimes more active than the parent compounds. All compounds impaired mussel health status, as indicated by the low to high stress levels assigned using the Mussel Expert System.

Keywords: Antidepressant; Biomarker; Early life stages; Emerging contaminants; Mytilus galloprovincialis; Pharmaceutical.