Skip to main content

Advertisement

Log in

In vivo exposure of marine mussels to venlafaxine: bioconcentration and metabolization

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Pharmaceuticals are present in natural waters, thus contributing to the general exposure of aquatic organisms, but few data are available on the accumulation of these substances in marine organisms. The present study evaluated the in vivo bioconcentration of an antidepressant—venlafaxine (VLF)—in marine mussels (Mytilus galloprovincialis) during 7 days of exposure at nominal 10 μg/L concentration, followed by a 7-day depuration period. The bioconcentration factor (BCF) was 265 mL/g dry weight (dw). VLF accumulation reached an average tissue concentration of 2146 ± 156 ng/g dw within 7 days, showing a first-order kinetics process. N-desmethylvenlafaxine (N-VLF) and O-desmethylvenlafaxine (O-VLF) metabolites were quantified in mussel tissues, whereas N,N-didesmethylvenlafaxine (NN-VLF) was only recorded as being detected. These three metabolites were also quantified in water, indicating an active metabolism and VLF excretion in Mediterranean mussels. Complementary experiments conducted at nominal concentrations of 1, 10, and 100 μg/L for 7 days confirmed the VLF bioconcentration and metabolism and allowed us to quantify a supplementary metabolite, i.e., N,O-didesmethylvenlafaxine (NO-VLF), in mussel tissues. These results encourage further research on a more complete characterization of metabolism and on any disturbances linked to bioconcentration of VLF on bivalves.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

References

  • Alygizakis NA, Gago-Ferrero P, Borova V, Pavlidou A, Hatzianestis I, Thomaidis N (2016) Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater. Sci Total Environ 541:1097–1105

    Article  CAS  Google Scholar 

  • Álvarez-Muñoz D, Rodríguez-Mozaz S, Maulvault AL, Tediosi A, Barceló D (2015) Occurrence of pharmaceuticals and endocrine disrupting compounds in macroalgaes, bivalves, and fish from coastal areas in Europe. Environ Res 143:56–64

    Article  Google Scholar 

  • Ariza-Castro N, Courant F, Dumas T, Marion B, Fenet H, Gomez E (2021) Elucidating venlafaxine metabolism in the Mediterranean Mussel (Mytilus galloprovincialis) through combined targeted and non-targeted approaches. Sci Total Environ 779:146387

    Article  CAS  Google Scholar 

  • Arnnok P, Singh RR, Burakham R, Perez-Fuentetaja A, Aga DS (2017) Selective uptake and bioaccumulation of antidepressants in fish from effluent-impacted Niagara River. Environ Sci Technol 51(18):10652–10662

    Article  CAS  Google Scholar 

  • Arpin-Pont L, Bueno MJ, Gomez E, Fenet H (2016) Occurrence of PPCPs in the marine environment: a review. Environ Sci Pollut Res 23(6):4978–4991

    Article  Google Scholar 

  • Aminot A, Rey F (2002) Chlorophyll a: determination by spectroscopic methods. ICES Techn Mar Environ Sci 30:1–18

    Google Scholar 

  • Boillot C, Martinez Bueno MJ, Munaron D, LeDreau M, Mathieu O, David A, Fenet H, Casellas C, Gomez E (2015) In vivo exposure of marine mussels to carbamazepine and10-hydroxy-10,11-dihydro-carbamazepine: bioconcentration and metabolization. Sci Total Environ 532:564–570

    Article  CAS  Google Scholar 

  • Chaty S, Rodius F, Vasseur P (2004) Comparative study of the expression of CYP1A and CYP4 genes in aquatic invertebrate (freshwater mussel, Unio tumidus) and vertebrate (rainbow trout, Oncorhynchus mykiss). Aquat Toxicol 69:81–93

    Article  CAS  Google Scholar 

  • Cerveny D, Brodin T, Fick J (2019) Bioconcentration and behavioral effects of four benzodiazepines and their environmentally relevant mixture in wild fish. Sci Total Environ 702(134780)

  • David A, Fenet H, Escande A, Munaron D, Maillot-Maréchal E, Aït-Aïssa S, Casellas C, Gomez E (2010) In Vitro biomonitoring of contamination by estrogenic compounds in coastal environments: comments on the use of M. galloprovincialis. Environ. Toxicol. 27(3):74–82

    Google Scholar 

  • Dehm J, Singh S, Fick J (2021) Screening of pharmaceuticals in coastal waters of the southern coast of Viti Levu in Fiji, South Pacific. Chemosphere. 276:130161

    Article  CAS  Google Scholar 

  • De Solla SR, Gilroy EAM, Klincka S, King LE, McInnisb R, Backus SM, Gillis PL (2016) Bioaccumulation of pharmaceuticals and personal care products in the unionid mussel Lasmigona costata in a river receiving wastewater effluent. Chemosphere 146:486–496

    Article  Google Scholar 

  • Dodder NG, Maruya KA, Ferguson PL, Klosterhaus S, La Guardia MJ, Lauensten GG, Ramirez J (2014) Occurrence of contaminants of emerging concern in mussels (Mytilus spp.) along the California coast and the influence of land use, storm water discharge, and treated wastewater effluent. Mar. Poll. Bull. 81(2):340–346

    CAS  Google Scholar 

  • Dumas T, Bonnefille B, Gomez E, Boccard J, Ariza CN, Fenet H, Courant F (2020) Metabolomics approach reveals disruption of metabolic pathways in the marine bivalve Mytilus galloprovincialis exposed to a WWTP effluent extract. Sci Total Environ 712:136551

    Article  CAS  Google Scholar 

  • EU (2008) Directive 2008/ 56/EC of the European Parliament and the Council of 17 June 2008 establishing a framework for community action in the field of marine environmental policy (Marine Strategy Framework Directive). Off J Eur Union L, 164 (19)

  • EU (2011) Commission Regulation (EU) No 253/2011 of 15 March 2011 amending Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards Annex XIII. European Commission, Brussels

    Google Scholar 

  • EU (2017). Commission Decision (EU) 2017/848 of 17 May 2017 laying down criteria and methodological standards on good environmental status of marine waters and specifications and standardised methods for monitoring and assessment, and repealing Decision 2010/477/EU. Off J Eur Union L, 125 (43)

  • EU (2020). Commission Implementing Decision (EU) 2020/1161 of 4 August 2020 establishing a watch list of substances for union-wide monitoring in the field of water policy pursuant to Directive 2008/105/EC of the European Parliament and of the Council. Off J Eur Union L, 257/32

  • Fernández-Rubio J, Rodríguez-Gil J, Postigo C, Mastroianni N, Lopez de Alda M, Barcelo D, Valcárcel Y (2019) Psychoactive pharmaceuticals and illicit drugs in coastal waters of North-Western Spain: environmental exposure and risk assessment. Chemosphere 224:379–389

    Article  Google Scholar 

  • Fong P, Ford A (2014) The biological effects of antidepressants on the molluscs and crustaceans: a review. Aquat Toxicol 151:4–13

    Article  CAS  Google Scholar 

  • Gomez E, Bachelot M, Boillot C, Munaron D, Chiron S, Casellas C, Fenet H (2012) Bioconcentration of two pharmaceuticals (benzodiazepines) and two personal care products (UV filters) in marine mussels (M. galloprovincialis) under controlled laboratory conditions. Environ Sci Pollut Res 19:2561–2569

    Article  CAS  Google Scholar 

  • Klosterhaus SL, Grace R, Hamilton MC, Yee D (2013) Method validation and reconnaissance of pharmaceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary. Environ Int 54(0):92–99

    Article  CAS  Google Scholar 

  • Kosma CI, Nannou CI, Boti VI, Albanis TA (2019) Psychiatrics and selected metabolites in hospital and urban wastewaters: occurrence, removal, mass loading, seasonal influence and risk assessment. Sci Total Environ 659:1473–1483

    Article  CAS  Google Scholar 

  • Lacaze E, Pédelucq J, Fortier M, Brousseau P, Auffret M, Budzinski H, Fournier M (2015) Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes. Environ Pollut 202:177–186

    Article  CAS  Google Scholar 

  • Lapworth DJ, Baran N, Stuart ME, Ward RS (2012) Emerging organic contaminants in groundwater: A review of sources, fate and occurrence. Environ Pollut 163:287–303

    Article  CAS  Google Scholar 

  • Martinez Bueno MJ, Boillot C, Fenet H, Chiron S, Casellas C, Gomez E (2013) Fast and easy extraction combined with high resolution-mass spectrometry for residue analysis of two anticonvulsants and their metabolites in marine mussels. J Chromatogr A 1305:27–34

    Article  CAS  Google Scholar 

  • McEneff G, Barron L, Kelleher B, Paull B, Quinn B (2014) A year-long study of the spatial occurrence and relative distribution of pharmaceutical residues in sewage effluent, receiving marine waters and marine bivalves. Sci Total Environ 476-477:317–326

    Article  CAS  Google Scholar 

  • Mzukisi ML, Ncube S, Tutu H, Richards H, Newman B, Ndungu K, Chimuka L (2020) Pharmaceuticals and their metabolites in the marine environment: sources, analytical methods and occurrence. Trends Environ Anal Chem 28:e00104

    Article  Google Scholar 

  • OECD Health Statistics 2019.

    Google Scholar 

  • EPA. US-EPA (2012) TSCA Work plan chemicals: methods document. U.S.Environmental Protection Agency. Office of PollutionPrevention and Toxics Report No, Washington, p 39

    Google Scholar 

  • Osores S, Lagos N, San MV, Manríquez P, Vargas C, Torres R, Navarro J, Poupin M, Saldías G, Lardies M (2017) Plasticity and inter-population variability in physiological and life-history traits of the mussel Mytilus chilensis: a reciprocal transplant experiment. J Exp Mar Biol Ecol 490:1–12

    Article  Google Scholar 

  • Pal A, Kyh G, Ayc L, Reinhard M (2010) (2010). Impacts of emerging organic contaminants on freshwater resources: review of recent occurrences, sources, fate and effects. Sci. Total Environ 408:6062–6069

    Article  CAS  Google Scholar 

  • Ricciardi A, Bourget E (1998) Weight -to-weight conversion factors for marine benthic macroinvertebrates. Mar Ecol Prog Ser 163:245–251

    Article  Google Scholar 

  • Rodrigues M, Rosa A, Fortunato AB (2021) Effects of climate change and anthropogenic pressures in the water quality of a coastal lagoon (Ria Formosa, Portugal). Sci Total Environ 780:146311

    Article  CAS  Google Scholar 

  • Rudorfer MV, Porter WZ (1997) The role of metabolites of antidepressants in the treatment of depression. CNS Drugs 7(4):273–312

    Article  CAS  Google Scholar 

  • Sangkuhl K, Stingl J, Turpeinen M, Altman R, Stein T (2014) PharmGKB summary: venlafaxine pathway. Pharmacogenet Genomics 24(1):62–72

    Article  CAS  Google Scholar 

  • Santos L, Maulvault AL, Jaen-Gil A, Marques A, Barcelo D, Rodríguez-Mozaz S (2020) Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach. Sci Total Environ 737:140226

    Article  CAS  Google Scholar 

  • Sehonova P, Svobodova Z, Dolezelova P, Vosmerova P, Faggio C (2018) Effects of waterborne antidepressants on non-target animals living in the aquatic environment: a review. Sci Total Environ 631-632:789–794

    Article  CAS  Google Scholar 

  • Serra-Compte A, Maulvault AL, Camacho C, Álvarez-Muñoz D, Barcelo D, Rodríguez-Mozaz S, Marques A (2018) Effects of water warming and acidification on bioconcentration, metabolization and depuration of pharmaceuticals and endocrine disrupting compounds in marine mussels (Mytilus galloprovincialis). Environ Pollut 236:824–834

    Article  CAS  Google Scholar 

  • Snyder MJ (1998) Cytochrome P450 enzymes belonging to the CYP4 family from marine invertebrates. Biochem Biophys Res Commun 249:187–190

    Article  CAS  Google Scholar 

  • Świacka K, Maculewicz J, Smolarz K, Szaniawska A, Caban M (2019) Mytilidae as model organisms in the marine ecotoxicology of pharmaceuticals - a review. Environ Pollut 254:113082

    Article  Google Scholar 

  • Verlicchi P, Al Aukidy M, Zambello E (2012) Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment-A review. Sci Total Environ 429:123–155

    Article  CAS  Google Scholar 

  • Zanette J, Jenny MJ, Goldstone JV, Parente T, Woodin BR, Bainy AC, Stegeman JJ (2013) Identification and expression of multiple CYP1-like and CYP3-like genes in the bivalve mollusk Mytilus edulis. Aquat Toxicol 128-129:101–112

    Article  CAS  Google Scholar 

  • Zenker A, Cicero MR, Prestinaci F, Bottoni P, Carere M (2014) Bioaccumulation and biomagnification potential of pharmaceuticals with a focus to the aquatic environment. J Environ Manag 133:378–387

    Article  CAS  Google Scholar 

  • Ziegler M, Banet M, Bauer R, Köhler HR, Stepinski S, Tisler S, Huhn C, Zwiener C, Triebskorn R (2021) Behavioral and developmental changes in brown trout after exposure to the antidepressant venlafaxine. Front Environ Sci 8:586584

    Article  Google Scholar 

Download references

Acknowledgements

The analyses were performed at the Platform on non-target environmental analysis (PONTEM), member of the MAMMA facility, Biocampus, Montpellier.

Funding

Funding support was obtained from the Agence Nationale de la Recherche (ANR), France, and the PEPSEA Project is acknowledged. Funding support was obtained from Sanofi Winthrop Industry. This research benefited from the support of the Chair Veolia Environment—HydroSciences: Risk analysis relating to emerging contaminants in water bodies.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the experiment, wrote, read, and approved the final manuscript.

Elena Gomez has coordinated the experimental procedures and the contribution of each of the authors.

Clothilde Boillot has mainly managed the experimental procedures.

Maria Jesus Martinez Bueno has validated the chemicals analyses procedures.

Dominique Munaron has managed the experimental mussel exposures.

Mathieu Olivier has contributed mainly to the discussion on pharmaceuticals metabolism.

Frédérique Courant has mainly contributed to the final discussion.

Hélène Fenet has coordinated the scientific project.

Corresponding author

Correspondence to Elena Gomez.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Responsible Editor: Cinta Porte

The analyses were performed at the Platform on non-target environmental analysis (PONTEM), member of the MAMMA facility, Biocampus, Montpellier.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 76 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gomez, E., Boillot, C., Martinez Bueno, M.J. et al. In vivo exposure of marine mussels to venlafaxine: bioconcentration and metabolization. Environ Sci Pollut Res 28, 68862–68870 (2021). https://doi.org/10.1007/s11356-021-14893-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-14893-4

Keywords

Navigation