Effects of norfluoxetine on mRNA expression levels, cellular defense mechanisms and histopathological alterations in the bivalve Mytilus trossulus (Mytilidae)

Norfluoxetine (NFLU) belongs to the most commonly found antidepressants in the aquatic environments worldwide. The aim of this study was to assess the multi-level biological response in the gills and digestive system of Mytilus trossulus exposed to 500 ng/L NFLU over six days. In mussels exposed to NFLU, catalase activity was significantly lower (3.87 ± 0.6 versus 6.86 ± 0.29 U/mg protein), while glutathione S-transferase activity significantly higher (173.01 ± 11.26 versus 152.12 ± 13.82 nmol/min/mg protein) as compared to control mussels. Aromatization efficiency, which is related to steroid metabolism, was higher in NFLU exposed mussels as compared to the control (12.88 ± 0.99 and 7.98 ± 0.92 pmol/h/mg protein, respectively). In the haemolymph of exposed mussels serotonin level decreased from 3.1 ± 1.5 ng/L (control) to 1.7 ± 0.6 ng/L. The expression of genes encoding proteins involved in the detoxification and inflammatory processes also differed. In the digestive system of exposed bivalves, CYP1L1 and CYP3AL1 genes were upregulated while PGY1 gene was downregulated. In the gills of NFLU-treated mussels the expression of CYP3AL1, CYP1L1, GSTϛ3, ATPase, MVP and 5-HTR genes were downregulated while PGY1 gene was upregulated. On the tissue level, the presence of progressive (inflammations, necrosis) and regressive (oedema, atrophy, degenerations) changes were found in gills and digestive system of exposed mussels. ATPase-driven imbalance in the osmotic regulation in the gills after exposure to NFLU may stimulate arise of gill lesions. Our results provide evidence for NFLU neuroendocrine modulating capacity as indicated by increased aromatization activity and changes in the serotonin signaling pathway.