Skip to main content
SpringerLink
Log in

Bioconcentration, behavioral, and biochemical effects of the non-steroidal anti-inflammatory drug diclofenac in Daphnia magna

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

Abstract

The non-steroidal anti-inflammatory drug (NSAID) diclofenac is one of the most frequently studied as well as controversially discussed pharmaceutically active drug on the subject of its relevance to the environment. This study was conducted to assess the bioconcentration potential of diclofenac and its behavioral and biochemical effects in Daphnia magna. The bioconcentration factors of diclofenac determined after 48 h of aqueous exposure in Daphnia magna were 70.94 and 8.02 for the nominal exposure concentrations of 5 and 100 μg/L, respectively. Diclofenac exposure obviously decreased the filtration and ingestion rates of the daphnids. A significant increase of the acetylcholinesterase activity that was observed in this study indicates that diclofenac might not have neurobehavioral toxicity in Daphnia magna. Significant induction of malondialdehyde content is an indication of overproduction of reactive oxygen species leading to oxidative damage in daphnids after diclofenac exposure. Moreover, significant inhibition of the superoxide dismutase, catalase, and glutathione reductase activities implies that the antioxidant defense system of Daphnia magna was overwhelmed. Also, significant inhibition of glutathione s-transferase activity might point to the fact that the enzyme was not capable to detoxify diclofenac in Daphnia magna. These findings indicate that diclofenac can accumulate and consequently stimulate behavioral and biochemical disturbances in Daphnia magna.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adam L, Katherine L, Erik TK (2011) Bioconcentration of the intense sweetener sucralose in a multitrophic battery of aquatic organisms. Environ Toxicol Chem 30:673–681

    Article  CAS  Google Scholar 

  • Arnot JA, Gobas FAPC (2006) A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ Rev 14:257–297

    Article  CAS  Google Scholar 

  • Barata C, Varo I, Navarro JC, Arun S, Porte C (2005) Antioxidant enzyme activities and lipid peroxidation in the freshwater cladoceran Daphnia magna exposed to redox cycling compounds. Comp Biochem Physiol C Toxicol Pharmacol 140:175–186

    Article  CAS  Google Scholar 

  • Barnes KK, Kolpin DW, Furlong ET, Zaugg SD, Meyer MT, Barber LB (2008) A national reconnaissance of pharmaceuticals and other organic wastewater contaminants in the United States — I) groundwater. Sci Total Environ 402:192–200

  • Bickley LK, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (2017) Bioavailability and kidney responses to diclofenac in the fathead minnow (Pimephales promelas). Environ Sci Technol 51:1764–1774

    Article  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Brown JN, Paxéus N, Förlin L, Larsson DJ (2007) Variations in bioconcentration of human pharmaceuticals from sewage effluents into fish blood plasma. Environ Toxicol Pharmacol 24:267–274

    Article  CAS  Google Scholar 

  • Buser H-R, Poiger T, Müller MD (1998) Occurrence and fate of the pharmaceutical drug diclofenac in surface waters: rapid photodegradation in a Lake. Environ Sci Technol 32:3449–3456

    Article  CAS  Google Scholar 

  • Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142:185–194

    Article  CAS  Google Scholar 

  • Contardo-Jara V, Lorenz C, Pflugmacher S, Nützmann G, Kloas W, Wiegand C (2011) Exposure to human pharmaceuticals carbamazepine, ibuprofen and Bezafibrate causes molecular effects in Dreissena polymorpha. Aquat Toxicol 105:428–437

    Article  CAS  Google Scholar 

  • Cunningham VL (2004) Special characteristics of pharmaceuticals related to environmental fate. In: Kümmerer K (ed) Pharmaceuticals in the environment: sources, fate, effects and risks. Springer Berlin Heidelberg, Berlin, pp 13–24

    Chapter  Google Scholar 

  • Ding J, Lu G, Liu J, Yang H, Li Y (2016) Uptake, depuration, and bioconcentration of two pharmaceuticals, roxithromycin and propranolol, in Daphnia magna. Ecotoxicol Environ Saf 126:85–93

    Article  CAS  Google Scholar 

  • Ding J, Zou H, Liu Q, Zhang S, Mamitiana Razanajatovo R (2017) Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna. Ecotoxicol Environ Saf 142:102–109

    Article  CAS  Google Scholar 

  • EU (2013) Directive 2013/39/EU of the European Parliament and of the council of 12 August 2013 amending directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy European Union off. J Eur Union L226

  • Ferrari B, Paxéus N, Giudice RL, Pollio A, Garric J (2003) Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 55:359–370

    Article  CAS  Google Scholar 

  • Ferrari B, Mons R, Vollat B, Fraysse B, Paxēaus N, Giudice RL, Pollio A, Garric J (2004) Environmental risk assessment of six human pharmaceuticals: are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ Toxicol Chem 23:1344–1354

    Article  CAS  Google Scholar 

  • Filip C, Erik K, Jerker F, Noomi A, Lars F, Joakim LDG (2011) Diclofenac in fish: blood plasma levels similar to human therapeutic levels affect global hepatic gene expression. Environ Toxicol Chem 30:2126–2134

    Article  CAS  Google Scholar 

  • Gan TJ (2010) Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin 26:1715–1731

    Article  CAS  Google Scholar 

  • Gauld DT (1951) The grazing rate of planktonic copepods. J Mar Biol Assoc U K 29:695–706

    Article  Google Scholar 

  • Gonzalez-Rey M, Bebianno MJ (2012) Does non-steroidal anti-inflammatory (NSAID) ibuprofen induce antioxidant stress and endocrine disruption in mussel Mytilus galloprovincialis? Environ Toxicol Pharmacol 33:361–371

    Article  CAS  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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  • Heberer T, Mechlinski A, Fanck B, Knappe A, Massmann G, Pekdeger A, Fritz B (2004) Field studies on the fate and transport of pharmaceutical residues in bank filtration. Ground Water Monit Remed 24:70–77

    Article  CAS  Google Scholar 

  • Holland (2018) EGU2018: New global models predict increasing pollution of rivers. https://www.dutchwatersector.com/news-events/news/30914-egu2018-new-global-models-predict-increasing-pollution-of-rivers.html. Accessed 21/10/2018

  • Islas-Flores H, Gómez-Oliván LM, Galar-Martínez M, Colín-Cruz A, Neri-Cruz N, García-Medina S (2013) Diclofenac-induced oxidative stress in brain, liver, gill and blood of common carp (Cyprinus carpio). Ecotoxicol Environ Saf 92:32–38

    Article  CAS  Google Scholar 

  • Jeong TY, Kim TH, Kim SD (2016) Bioaccumulation and biotransformation of the beta-blocker propranolol in multigenerational exposure to Daphnia magna. Environ Pollut 216:811–818

    Article  CAS  Google Scholar 

  • Jux U, Baginski RM, Arnold H-G, Krönke M, Seng PN (2002) Detection of pharmaceutical contaminations of river, pond, and tap water from Cologne (Germany) and surroundings. Int J Hyg Environ Health 205:393–398

    Article  CAS  Google Scholar 

  • Kallio J-M, Lahti M, Oikari A, Kronberg L (2010) Metabolites of the aquatic pollutant diclofenac in fish bile. Environ Sci Technol 44:7213–7219

    Article  CAS  Google Scholar 

  • Kappus H (1985) Lipid peroxidation: mechanisms, analysis, enzymology and biological relevance. In: Sies H (ed) Oxidative stress. Academic, New York, pp 273–310

    Chapter  Google Scholar 

  • Kim HY, Jeon J, Hollender J, Yu S, Kim SD (2014) Aqueous and dietary bioaccumulation of antibiotic tetracycline in D. magna and its multigenerational transfer. J Hazard Mater 279:428–435

    Article  CAS  Google Scholar 

  • Li Z-H, Velisek J, Zlabek V, Grabic R, Machova J, Kolarova J, Randak T (2010) Hepatic antioxidant status and hematological parameters in rainbow trout, Oncorhynchus mykiss, after chronic exposure to carbamazepine. Chem Biol Interact 183:98–104

    Article  CAS  Google Scholar 

  • Liang R, He J, Shi Y, Li Z, Sarvajayakesavalu S, Baninla Y, Guo F, Chen J, Xu X, Lu Y (2017) Effects of perfluorooctane sulfonate on immobilization, heartbeat, reproductive and biochemical performance of Daphnia magna. Chemosphere 168:1613–1618

    Article  CAS  Google Scholar 

  • Liu J, Lu G, Ding J, Zhang Z, Wang Y (2014a) Tissue distribution, bioconcentration, metabolism, and effects of erythromycin in crucian carp (Carassius auratus). Sci Total Environ 490:914–920

    Article  CAS  Google Scholar 

  • Liu J, Lu G, Wang Y, Yan Z, Yang X, Ding J, Jiang Z (2014b) Bioconcentration, metabolism, and biomarker responses in freshwater fish Carassius auratus exposed to roxithromycin. Chemosphere 99:102–108

    Article  CAS  Google Scholar 

  • Liu J, Lu G, Yang H, Yan Z, Wang Y, Wang P (2016) Bioconcentration and metabolism of ketoconazole and effects on multi-biomarkers in crucian carp (Carassius auratus). Chemosphere 150:145–151

    Article  CAS  Google Scholar 

  • Liu J, Lu G, Cai Y, Wu D, Yan Z, Wang Y (2017) Modulation of erythromycin-induced biochemical responses in crucian carp by ketoconazole. Environ Sci Pollut Res 24:5285–5292

    Article  CAS  Google Scholar 

  • Liu Y, Guo R, Tang S, Zhu F, Zhang S, Yan Z, Chen J (2018) Single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 on the feeding activity of Daphnia magna: from behavior assessment to neurotoxicity. Chemosphere 195:542–550

    Article  CAS  Google Scholar 

  • Lonappan L, Brar SK, Das RK, Verma M, Surampalli RY (2016) Diclofenac and its transformation products: environmental occurrence and toxicity - a review. Environ Int 96:127–138

    Article  CAS  Google Scholar 

  • Loos R, Gawlik BM, Locoro G, Rimaviciute E, Contini S, Bidoglio G (2009) EU-wide survey of polar organic persistent pollutants in European river waters. Environ Pollut 157:561–568

    Article  CAS  Google Scholar 

  • Ma J, Liu Y, Niu D, Li X (2015) Effects of chlorpyrifos on the transcription of CYP3A cDNA, activity of acetylcholinesterase, and oxidative stress response of goldfish (Carassius auratus). Environ Toxicol 30:422–429

    Article  CAS  Google Scholar 

  • Memmert U, Peither A, Burri R, Weber K, Schmidt T, Sumpter JP, Hartmann A (2013) Diclofenac: new data on chronic toxicity and bioconcentration in fish. Environ Toxicol Chem 32:442–452

    Article  CAS  Google Scholar 

  • Meredith-Williams M, Carter LJ, Fussell R, Raffaelli D, Ashauer R, Boxall ABA (2012) Uptake and depuration of pharmaceuticals in aquatic invertebrates. Environ Pollut 165:250–258

    Article  CAS  Google Scholar 

  • Milan M, Pauletto M, Patarnello T, Bargelloni L, Marin MG, Matozzo V (2013) Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen. Aquat Toxicol 126:17–29

    Article  CAS  Google Scholar 

  • Mwaanga P, Carraway ER, van den Hurk P (2014) The induction of biochemical changes in Daphnia magna by CuO and ZnO nanoparticles. Aquat Toxicol 150:201–209

    Article  CAS  Google Scholar 

  • Oliveira LL, Antunes SC, Gonçalves F, Rocha O, Nunes B (2015) Evaluation of ecotoxicological effects of drugs on Daphnia magna using different enzymatic biomarkers. Ecotoxicol Environ Saf 119:123–131

    Article  CAS  Google Scholar 

  • Organization for Economic Cooperation and Development (OECD) (2004) Guidelines for testing of chemicals no. 202: Daphnia magna acute immobilization test. Paris

  • Pirow R, Wollinger F, Paul RJ (1999) The sites of respiratory gas exchange in the planktonic crustacean Daphnia magna: an in vivo study employing blood haemoglobin as an internal oxygen probe. J Exp Biol 202:3089–3099

    Google Scholar 

  • Pohanka M (2011) Cholinesterases, a target of pharmacology and toxicology. Biomed Pap Med Fac Palacky Olomouc Czech Repub 155:219–229

    Article  CAS  Google Scholar 

  • Pohanka M (2012) Acetylcholinesterase inhibitors: a patent review (2008–present). Expert Opin Ther Pat 22:871–886

    Article  CAS  Google Scholar 

  • Porter K, Orcutt J Jr, Gerritsen J (1983) Functional response and fitness in a generalist filter feeder, Daphnia magna (Cladocera: Crustacea). Ecology 64:735–742

    Article  Google Scholar 

  • Saravanan M, Karthika S, Malarvizhi A, Ramesh M (2011) Ecotoxicological impacts of clofibric acid and diclofenac in common carp (Cyprinus carpio) fingerlings: hematological, biochemical, ionoregulatory and enzymological responses. J Hazard Mater 195:188–194

    Article  CAS  Google Scholar 

  • Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Toxic effects of the non-steroidal anti-inflammatory drug diclofenac: part I: histopathological alterations and bioaccumulation in rainbow trout. Aquat Toxicol 68:141–150

    Article  CAS  Google Scholar 

  • Teijon G, Candela L, Tamoh K, Molina-Díaz A, Fernández-Alba A (2010) Occurrence of emerging contaminants, priority substances (2008/105/CE) and heavy metals in treated wastewater and groundwater at Depurbaix facility (Barcelona, Spain). Sci Total Environ 408:3584–3595

    Article  CAS  Google Scholar 

  • Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260

    Article  CAS  Google Scholar 

  • Triebskorn R, Schwarz S, Köhler H, Berg K, Jungmann D, Frey M, Oehlmann J, Oetken M (2014) From theory to reality - evaluation of suitable organisms and test systems for the biomonitoring of pharmaceuticals - part I: literature review. UBA Texte, Umweltbundesamt, Dessau-Rosslau

    Google Scholar 

  • USEPA (2007) Method 1694: pharmaceuticals and personal care products in water, soil, sediment, and biosolids by HPLC/MS/MS Washington, DC EPA-821-R-08-002:1-77

  • Van der Oost R, Beyer J, Vermeulen NP (2003) Fish bioaccumulation and biomarkers in environmental risk assessment: a review. Environ Toxicolo Pharmacol 13:57–149

    Article  Google Scholar 

  • Yonar ME, Yonar SM, Ural MŞ, Silici S, Düşükcan M (2012) Protective role of propolis in chlorpyrifos-induced changes in the haematological parameters and the oxidative/antioxidative status of Cyprinus carpio carpio. Food Chem Toxicol 50:2703–2708

    Article  CAS  Google Scholar 

  • Zaltauskaite J, Miskelyte D (2018) Biochemical and life cycle effects of triclosan chronic toxicity to earthworm Eisenia fetida. Environ Sci Pollut Res:1–9

  • Zhang X, Yang L, Zhao Q, Caen J, He H, Jin Q, Guo L, Alemany M, Zhang L, Shi Y (2002) Induction of acetylcholinesterase expression during apoptosis in various cell types. Cell Death Differ 9:790–800

    Article  CAS  Google Scholar 

  • Zhao H, Liu S, Chen J, Jiang J, Xie Q, Quan X (2015) Biological uptake and depuration of sulfadiazine and sulfamethoxazole in common carp (Cyprinus carpio). Chemosphere 120:592–597

    Article  CAS  Google Scholar 

  • Zhao J-L, Furlong ET, Schoenfuss HL, Kolpin DW, Bird KL, Feifarek DJ, Schwab EA, Ying G-G (2017) Uptake and disposition of select pharmaceuticals by bluegill exposed at constant concentrations in a flow-through aquatic exposure system. Environ Sci Technol 51:4434–4444

    Article  CAS  Google Scholar 

  • Zhu X, Chang Y, Chen Y (2010) Toxicity and bioaccumulation of TiO2 nanoparticle aggregates in Daphnia magna. Chemosphere 78:209–215

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (Grant 51769034, 51609066), the Fundamental Research Funds for the Central Universities (Grant 2018B43614), the Program for Scientific Research Innovation Team in Colleges and Universities of Tibet Autonomous Region, and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Author information

Authors and Affiliations

  1. Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing, 210098, China

    Matthew Nkoom, Guanghua Lu, Jianchao Liu, Huike Dong & Haohan Yang

  2. Water Conservancy Project & Civil Engineering College, Tibet Agriculture & Animal Husbandry University, Linzhi, 860000, China

    Guanghua Lu

Authors
  1. Matthew Nkoom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guanghua Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianchao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huike Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haohan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guanghua Lu.

Additional information

Responsible editor: Cinta Porte

Publisher’s Note

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

Electronic supplementary material

ESM 1

(DOCX 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nkoom, M., Lu, G., Liu, J. et al. Bioconcentration, behavioral, and biochemical effects of the non-steroidal anti-inflammatory drug diclofenac in Daphnia magna. Environ Sci Pollut Res 26, 5704–5712 (2019). https://doi.org/10.1007/s11356-018-04072-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-018-04072-3

Keywords

Search

Navigation