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Effects of Carbamazepine in Bivalves: A Review

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Reviews of Environmental Contamination and Toxicology Volume 254

Part of the book series: Reviews of Environmental Contamination and Toxicology ((RECT,volume 254))

Abstract

Carbamazepine (CBZ) is among the ten most frequent pharmaceuticals that occur in the aquatic systems, with known effects on inhabiting organisms, including bivalves. Bivalves are important species in coastal ecosystems, often exhibiting a dominant biomass within invertebrate communities. These organisms play a major role in the functioning of the ecosystem and particularly in food webs (as suspension-feeders) and represent a significant fraction of the fisheries resource. They also have strong interactions with the environment, water and sediment and are considered good bioindicator species. The present paper reviews the known literature on the impacts of CBZ in biological endpoints of marine bivalves exposed to environmentally and non-environmentally relevant concentrations, highlighting differences in terms of biological responses, associated with exposure period, concentrations tested, and species used. Overall, the literature available showed that CBZ induces individual and sub-individual effects in marine bivalves (adults and life stages) and the most common effect reported was the induction of oxidative stress.

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References

  • Abdelhafidh K, Ali M, Hassen K, Badreddine S, Jaume A, Sandra P, Ethel E, Damià B, Hamouda B, Ezzeddine M (2018) Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its effects in biochemical responses. Xenobiotica 48:727–733

    CAS  Google Scholar 

  • Aguirre-Martínez GV, Buratti S, Fabbri E, DelValls AT, Martín-Díaz ML (2013) Using lysosomal membrane stability of haemocytes in Ruditapes philippinarum as a biomarker of cellular stress to assess contamination by caffeine, ibuprofen, carbamazepine and novobiocin. J Environ Sci 25:1408–1418

    Google Scholar 

  • Aguirre-Martínez GV, DelValls TA, Martín-Díaz ML (2016) General stress, detoxification pathways, neurotoxicity and genotoxicity evaluated in Ruditapes philippinarum exposed to human pharmaceuticals. Ecotoxicol Environ Saf 124:18–31

    Google Scholar 

  • Almeida Â, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E, Freitas R (2014) Presence of the pharmaceutical drug carbamazepine in coastal systems: effects on bivalves. Aquat Toxicol 156:74–87

    CAS  Google Scholar 

  • Almeida Â, Freitas R, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E (2015) Chronic toxicity of the antiepileptic carbamazepine on the clam Ruditapes philippinarum. Comp Biochem Physiol C Toxicol Pharmacol 172:26–35

    Google Scholar 

  • Almeida Â, Calisto V, Domingues MRM, Esteves VI, Schneider RJ, Soares AM, Figueira E, Freitas R (2017a) Comparison of the toxicological impacts of carbamazepine and a mixture of its photodegradation products in Scrobicularia plana. J Hazard Mater 323:220–232

    CAS  Google Scholar 

  • Almeida Â, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E, Freitas R (2017b) Ecotoxicity of the antihistaminic drug cetirizine to Ruditapes philippinarum clams. Sci Total Environ 601:793–801

    Google Scholar 

  • Almeida Â, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E, Freitas R (2017c) Toxicity associated to uptake and depuration of carbamazepine in the clam Scrobicularia plana under a chronic exposure. Sci Total Environ 580:1129–1145

    CAS  Google Scholar 

  • Almeida Â, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E, Freitas R (2018a) Effects of single and combined exposure of pharmaceutical drugs (carbamazepine and cetirizine) and a metal (cadmium) on the biochemical responses of R. philippinarum. Aquat Toxicol 198:10–19

    CAS  Google Scholar 

  • Almeida Â, Freitas R, Calisto V, Esteves VI, Schneider RJ, Soares AM, Figueira E, Campos B, Barata C (2018b) Effects of carbamazepine and cetirizine under an ocean acidification scenario on the biochemical and transcriptome responses of the clam Ruditapes philippinarum. Environ Pollut 235:857–868

    CAS  Google Scholar 

  • Ambrósio AF, Soares-da-Silva P, Carvalho CM, Carvalho AP (2002) Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, BIA 2-093, and BIA 2-024. Neurochem Res 27:121–130

    Google Scholar 

  • Anzenbacher P, Anzenbacherova E (2001) Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci 58:737–747

    CAS  Google Scholar 

  • Bayen S, Zhang H, Desai MM, Ooi SK, Kelly BC (2013) Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore’s marine environment: influence of hydrodynamics and physical–chemical properties. Environ Pollut 182:1–8

    CAS  Google Scholar 

  • Bazinet RP, Rao JS, Chang L, Rapoport SI, Lee H-J (2006) Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder. Biol Psychiatry 59:401–407

    CAS  Google Scholar 

  • Beutler AS, Li S, Nicol R, Walsh MJ (2005) Carbamazepine is an inhibitor of histone deacetylases. Life Sci 76:3107–3115

    CAS  Google Scholar 

  • Biel-Maeso M, Baena-Nogueras RM, Corada-Fernández C, Lara-Martín PA (2018) Occurrence, distribution and environmental risk of pharmaceutically active compounds (PhACs) in coastal and ocean waters from the Gulf of Cadiz (SW Spain). Sci Total Environ 612:649–659

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Brandts I, Teles M, Gonçalves AP, Barreto A, Franco-Martinez L, Tvarijonaviciute A, Martins MA, Soares A, Tort L, Oliveira M (2018) Effects of nanoplastics on Mytilus galloprovincialis after individual and combined exposure with carbamazepine. Sci Total Environ 643:775–784

    CAS  Google Scholar 

  • Brausch JM, Connors KA, Brooks BW, Rand GM (2012) Human pharmaceuticals in the aquatic environment: a review of recent toxicological studies and considerations for toxicity testing. In: Whitacre DM (ed) Reviews of environmental contamination and toxicology, Reviews of environmental contamination and toxicology, vol 218. Springer, Boston, pp 1–99

    Google Scholar 

  • Bueno MM, Gomez MJ, Herrera S, Hernando MD, Agüera A, Fernández-Alba AR (2012) Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: two years pilot survey monitoring. Environ Pollut 164:267–273

    CAS  Google Scholar 

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

    Google Scholar 

  • Calisto V, Bahlmann A, Schneider RJ, Esteves VI (2011) Application of an ELISA to the quantification of carbamazepine in ground, surface and wastewaters and validation with LC–MS/MS. Chemosphere 84:1708–1715

    CAS  Google Scholar 

  • Chen G, Pan B, Hawver DB, Wright CB, Potter WZ, Manji HK (1996) Attenuation of cyclic AMP production by carbamazepine. J Neurochem 67:2079–2086

    CAS  Google Scholar 

  • Clara M, Strenn B, Kreuzinger N (2004) Carbamazepine as a possible anthropogenic marker in the aquatic environment: investigations on the behaviour of carbamazepine in wastewater treatment and during groundwater infiltration. Water Res 38:947–954

    CAS  Google Scholar 

  • Di Poi C, Costil K, Bouchart V, Halm-Lemeille M-P (2018) Toxicity assessment of five emerging pollutants, alone and in binary or ternary mixtures, towards three aquatic organisms. Environ Sci Pollut Res 25:6122–6134

    Google Scholar 

  • Ebele AJ, Abdallah MA-E, Harrad S (2017) Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment. Emerg Contam 3:1–16

    Google Scholar 

  • Fabbri E, Capuzzo A (2010) Cyclic AMP signaling in bivalve molluscs: an overview. J Exp Zool A Ecol Genet Physiol 313:179–200

    Google Scholar 

  • Fabbri E, Franzellitti S (2016) Human pharmaceuticals in the marine environment: focus on exposure and biological effects in animal species. Environ Toxicol Chem 35:799–812

    CAS  Google Scholar 

  • Franzellitti S, Striano T, Valbonesi P, Fabbri E (2016) Insights into the regulation of the MXR response in haemocytes of the Mediterranean mussel (Mytilus galloprovincialis). Fish Shellfish Immunol 58:349–358

    CAS  Google Scholar 

  • Franzellitti S, Striano T, Pretolani F, Fabbri E (2017) Investigating appearance and regulation of the MXR phenotype in early embryo stages of the Mediterranean mussel (Mytilus galloprovincialis). Comp Biochem Physiol C Toxicol Pharmacol 199:1–10

    CAS  Google Scholar 

  • Freitas R, Almeida Â, Calisto V, Velez C, Moreira A, Schneider RJ, Esteves VI, Wrona FJ, Soares AM, Figueira E (2015a) How life history influences the responses of the clam Scrobicularia plana to the combined impacts of carbamazepine and pH decrease. Environ Pollut 202:205–214

    CAS  Google Scholar 

  • Freitas R, Almeida Â, Pires A, Velez C, Calisto V, Schneider RJ, Esteves VI, Wrona FJ, Figueira E, Soares AM (2015b) The effects of carbamazepine on macroinvertebrate species: comparing bivalves and polychaetes biochemical responses. Water Res 85:137–147

    CAS  Google Scholar 

  • Freitas R, Almeida Â, Calisto V, Velez C, Moreira A, Schneider RJ, Esteves VI, Wrona FJ, Figueira E, Soares AMVM (2016) The impacts of pharmaceutical drugs under ocean acidification: new data on single and combined long-term effects of carbamazepine on Scrobicularia plana. Sci Total Environ 541:977–985

    CAS  Google Scholar 

  • Gaw S, Thomas KV, Hutchinson TH (2014) Sources, impacts and trends of pharmaceuticals in the marine and coastal environment. Philos Trans R Soc B Biol Sci 369:20130572

    Google Scholar 

  • Gonzalez-Rey M, Bebianno MJ (2014) Effects of non-steroidal anti-inflammatory drug (NSAID) diclofenac exposure in mussel Mytilus galloprovincialis. Aquat Toxicol 148:221–230

    CAS  Google Scholar 

  • Halling-Sørensen B, Nielsen SN, Lanzky PF, Ingerslev F, Lützhøft HH, Jørgensen S (1998) Occurrence, fate and effects of pharmaceutical substances in the environment–a review. Chemosphere 36:357–393

    Google Scholar 

  • Honkoop PJ, Luttikhuizen PC, Piersma T (1999) Experimentally extending the spawning season of a marine bivalve using temperature change and fluoxetine as synergistic triggers. Mar Ecol Prog Ser 180:297–300

    Google Scholar 

  • Houeto P, Carton A, Guerbet M, Mauclaire A-C, Gatignol C, Lechat P, Masset D (2012) Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine. Regul Toxicol Pharmacol 62:41–48

    CAS  Google Scholar 

  • Juhel G, Benotti S, Goh C, Lee WK, Kelly BC (2017) Use of a suite of biomarkers to assess the effects of carbamazepine, bisphenol A, atrazine, and their mixtures on green mussels, Perna viridis. Environ Toxicol Chem 36:429–441

    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 54:92–99

    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

    CAS  Google Scholar 

  • Luis LG, Barreto Â, Trindade T, Soares AM, Oliveira M (2016) Effects of emerging contaminants on neurotransmission and biotransformation in marine organisms—an in vitro approach. Mar Pollut Bull 106:236–244

    CAS  Google Scholar 

  • Magnusson MO, Dahl M-L, Cederberg J, Karlsson MO, Sandström R (2008) Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther 84:52–62

    CAS  Google Scholar 

  • Martin-Diaz L, Franzellitti S, Buratti S, Valbonesi P, Capuzzo A, Fabbri E (2009) Effects of environmental concentrations of the antiepileptic drug carbamazepine on biomarkers and cAMP-mediated cell signaling in the mussel Mytilus galloprovincialis. Aquat Toxicol 94:177–185

    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 476:317–326

    Google Scholar 

  • Monteiro SC, Boxall AB (2010) Occurrence and fate of human pharmaceuticals in the environment. In: Reviews of environmental contamination and toxicology. Springer, Berlin, pp 53–154

    Google Scholar 

  • Moreno-González R, Rodríguez-Mozaz S, Huerta B, Barceló D, León VM (2016) Do pharmaceuticals bioaccumulate in marine molluscs and fish from a coastal lagoon? Environ Res 146:282–298

    Google Scholar 

  • Motohashi N, Ikawa K, Kariya T (1989) GABAB receptors are up-regulated by chronic treatment with lithium or carbamazepine. GABA hypothesis of affective disorders? Eur J Pharmacol 166:95–99

    CAS  Google Scholar 

  • Nödler K, Voutsa D, Licha T (2014) Polar organic micropollutants in the coastal environment of different marine systems. Mar Pollut Bull 85:50–59

    Google Scholar 

  • Oliveira P, Almeida Â, Calisto V, Esteves VI, Schneider RJ, Wrona FJ, Soares AM, Figueira E, Freitas R (2017) Physiological and biochemical alterations induced in the mussel Mytilus galloprovincialis after short and long-term exposure to carbamazepine. Water Res 117:102–114

    CAS  Google Scholar 

  • Powell EN, Cummins H (1985) Are molluscan maximum life spans determined by long-term cycles in benthic communities? Oecologia 67:77–182

    Google Scholar 

  • Prichard E, Granek EF (2016) Effects of pharmaceuticals and personal care products on marine organisms: from single-species studies to an ecosystem-based approach. Environ Sci Pollut Res 23:22365–22384

    Google Scholar 

  • Regoli F, Giuliani ME (2014) Oxidative pathways of chemical toxicity and oxidative stress biomarkers in marine organisms. Mar Environ Res 93:106–117

    Google Scholar 

  • Rodrigues J, Albino S, Silva S, Cravo A, Cardoso VV, Benoliel MJ, Almeida CM (2019) Development of a multiresidue method for the determination of 24 pharmaceuticals in clams by QuEChERS and liquid chromatography-triple quadrupole tandem mass spectrometry. Food Anal Methods 12:838–851

    Google Scholar 

  • Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21:172–188

    Google Scholar 

  • Solé M, Shaw JP, Frickers PE, Readman JW, Hutchinson TH (2010) Effects on feeding rate and biomarker responses of marine mussels experimentally exposed to propranolol and acetaminophen. Anal Bioanal Chem 396:649–656

    Google Scholar 

  • Sousa JCG, Ribeiro AR, Barbosa MO, Pereira MFR, Silva AMT (2018) A review on environmental monitoring of water organic pollutants identified by EU guidelines. J Hazard Mater 344:146–162

    CAS  Google Scholar 

  • Trombini C, Hampel M, Blasco J (2019) Assessing the effect of human pharmaceuticals (carbamazepine, diclofenac and ibuprofen) on the marine clam Ruditapes philippinarum: an integrative and multibiomarker approach. Aquat Toxicol 208:146–156

    CAS  Google Scholar 

  • Tsiaka P, Tsarpali V, Ntaikou I, Kostopoulou MN, Lyberatos G, Dailianis S (2013) Carbamazepine-mediated pro-oxidant effects on the unicellular marine algal species Dunaliella tertiolecta and the hemocytes of mussel Mytilus galloprovincialis. Ecotoxicology 22:1208–1220

    CAS  Google Scholar 

  • Viarengo A, Canesi L (1991) Mussels as biological indicators of pollution. Aquaculture 94:225–243

    Google Scholar 

  • Voultsiadou E, Koutsoubas D, Achparaki M (2010) Bivalve mollusc exploitation in Mediterranean coastal communities: an historical approach. J Biol Res 13:35

    Google Scholar 

  • Wille K, Kiebooms JA, Claessens M, Rappé K, Bussche JV, Noppe H, Van Praet N, De Wulf E, Van Caeter P, Janssen CR (2011) Development of analytical strategies using U-HPLC-MS/MS and LC-ToF-MS for the quantification of micropollutants in marine organisms. Anal Bioanal Chem 400:1459–1472

    CAS  Google Scholar 

  • Zhang Y, Geißen S-U, Gal C (2008) Carbamazepine and diclofenac: removal in wastewater treatment plants and occurrence in water bodies. Chemosphere 73:1151–1161

    CAS  Google Scholar 

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Acknowledgments

Ângela Almeida benefited from PhD grant (SFRH/BD/110218/2015) given by the National Funds through the Portuguese Science Foundation (FCT), supported by FSE and Programa Operacional Capital Humano (POCH) and European Union. Rosa Freitas was funded by national funds (OE), through FCT-Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. This work was also financially supported by the project BISPECIAl: BIvalveS under Polluted Environment and ClImate chAnge PTDC/CTA-AMB/28425/2017 (POCI-01-0145-FEDER-028425) funded by FEDER, through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE), through FCT/MCTES. Thanks are also due to Integrated Programme of SR&TD “Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate” (reference Centro-01-0145-FEDER-000018), co-funded by Centro 2020 program, Portugal 2020, European Union, through the European Regional Development Fund. Thanks are also due for the financial support to CESAM (UIDB/50017/2020 + UIDP/50017/2020). This manuscript was English revised by Gabinete de Tradução, Revisão e Comunicação Técnica, University of Aveiro.

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The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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Authors and Affiliations

  1. Biology Department and CESAM, University of Aveiro, Aveiro, Portugal

    Ângela Almeida, Amadeu M. V. M. Soares & Rosa Freitas

  2. Chemistry Department and CESAM, University of Aveiro, Aveiro, Portugal

    Valdemar I. Esteves

Authors
  1. Ângela Almeida
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  2. Valdemar I. Esteves
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  3. Amadeu M. V. M. Soares
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  4. Rosa Freitas
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Correspondence to Rosa Freitas .

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  1. University of Amsterdam, Amsterdam, The Netherlands

    Pim de Voogt

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Almeida, Â., Esteves, V.I., Soares, A.M.V.M., Freitas, R. (2020). Effects of Carbamazepine in Bivalves: A Review. In: de Voogt, P. (eds) Reviews of Environmental Contamination and Toxicology Volume 254. Reviews of Environmental Contamination and Toxicology, vol 254. Springer, Cham. https://doi.org/10.1007/398_2020_51

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