Journal of Literature Pharmacy Sciences

Antidepresanların Biyoakümülasyonuna Bağlı Ekotoksisite Riski: Sistematik Derleme
Risk of Ecotoxicity Due to Bioaccumulation of Antidepressants: Systematic Review
Hande YÜCEa, Songül ÜNÜVARa
aİnönü Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Malatya, Türkiye
J Lit Pharm Sci. 2022;11(2):152-8
doi: 10.5336/pharmsci.2021-87716
Article Language: TR
Full Text
ÖZET
İlaçlar, önemli çevresel kirleticiler arasında yer almaktadırlar. Antidepresan ilaçlar, hem yer altı hem de yer üstü sularında sıklıkla rastlanan kontaminantlardır. Antidepresan ilaçların su canlılarında tespit edilmesinin 2 nedeni vardır. Birincisi dünya genelinde yaygın kullanımları, ikincisi ise su canlılarının farklı dokularında birikmeleridir. Bazı balıklar ve yumuşakçalar gibi endemik su hayvanları, dokularında biyolojik olarak farklı antidepresanları biriktirmektedirler. Bu nedenle hedef olmayan birçok organizmayı etkileme potansiyeline sahiptirler. Antidepresanlar, dopamin, norepinefrin ve serotonin gibi nörotransmitterlerle etkileşime girerek santral sinir sistemini doğrudan etkileyen ilaçlardır. Su canlılarında, bu etkilerinin dışında da etkileri gözlenmektedir. Bu ilaçların dünya çapında artan kullanımına bağlı olarak, kentsel sularda, yer altı sularında, nehirlerlerde ve okyanuslarda yaygın tespit edilmektedirler. Ayrıca şu anda mevcut olan atık su arıtma tesisleri, ilaç kalıntılarını uzaklaştıracak şekilde dizayn edilmemiştir. Sulardaki ilaç kontaminasyonu, önümüzdeki yıllarda artacak gibi görünmektedir. Çünkü mevcut koronavirüs hastalığı-2019 pandemisi, dünya çapında genel depresyon ve anksiyeteyi tetikleyerek, antidepresan kullanımını ve dolayısıyla çevrede tespit edilen konsantrasyonlarını artırmıştır. Çevresel ilaç kontaminasyonu, bilimsel belirsizliklerin eşlik ettiği yaygın bir sorundur. Olası çözümler arasında, ilaçları akılcı kullanmak, çevre dostu ilaçlar reçete etmek, biyolojik olarak daha kolay parçalanan farmasötikler tasarlamak, çevre ve sağlık bilimleri arasındaki koordinasyonu ve iş birliğini geliştirmek sayılabilir. Bu derlemede, bazı antidepresanların yer altı ve yer üstü sulardaki kontaminasyonuna bağlı su canlıları üzerindeki biyoakümülasyonundan ve ekotoksikolojik etkilerinden bahsedilmektedir.

Anahtar Kelimeler: Antidepresanlar; çevre kirleticileri; ilaç kontaminasyonu; biyoakümülasyon
ABSTRACT
Drugs are among the important environmental pollutants. Antidepressant drugs are frequently found contaminants in both ground and surface waters. There are 2 reasons why antidepressant drugs are detected in aquatic organisms. The first is their widespread use throughout the world, and the second is their accumulation in different tissues of aquatic organisms. Endemic aquatic animals, such as some fish and mollusks, accumulate biologically different antidepressants in their tissues. Therefore, they have the potential to affect many non-target organisms. Antidepressants are drugs that directly affect the central nervous system by interacting with neurotransmitters such as dopamine, norepinephrine, and serotonin. Apart from these effects, effects are also observed in aquatic organisms. Due to the increasing use of these drugs worldwide, they are widely detected in urban waters, groundwater, rivers and oceans. In addition, currently existing wastewater treatment plants are not designed to remove drug residues. Drug contamination in waters is likely to increase in the coming years. Because the current coronavirus disease-2019 pandemic has triggered general depression and anxiety worldwide, increasing the use of antidepressants and thus their concentrations detected in the environment. Environmental drug contamination is a common problem accompanied by scientific uncertainties. Possible solutions include using drugs rationally, prescribing environmentally friendly drugs, designing more biodegradable pharmaceuticals, and improving coordination and collaboration between environmental and health sciences. In this review, the bioaccumulation and ecotoxicological effects of some antidepressants on aquatic organisms due to the contamination of underground and surface waters are mentioned.

Keywords: Antidepressants; environmental pollutants; drug contamination; bioaccumulation
REFERENCES:
  1. Grabicova K, Grabic R, Fedorova G, Fick J, Cerveny D, Kolarova J, et al. Bioaccumulation of psychoactive pharmaceuticals in fish in an effluent dominated stream. Water Res. 2017;124:654-62. [Crossref]  [PubMed] 
  2. Miller TH, Bury NR, Owen SF, MacRae JI, Barron LP. A review of the pharmaceutical exposome in aquatic fauna. Environ Pollut. 2018;239:129-46. [Crossref]  [PubMed]  [PMC] 
  3. Fatta-Kassinos D, Meric S, Nikolaou A. Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal Bioanal Chem. 2011;399(1):251-75. [Crossref]  [PubMed] 
  4. Rossi A, Barraco A, Donda P. Fluoxetine: a review on evidence based medicine. Ann Gen Hosp Psychiatry. 2004;3(1):2. [Crossref]  [PubMed]  [PMC] 
  5. 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. 2020. [Link] 
  6. Silva VH, Dos Santos Batista AP, Silva Costa Teixeira AC, Borrely SI. Degradation and acute toxicity removal of the antidepressant Fluoxetine (Prozac(®)) in aqueous systems by electron beam irradiation. Environ Sci Pollut Res Int. 2016;23(12):11927-36. [Crossref]  [PubMed] 
  7. Lajeunesse A, Smyth SA, Barclay K, Sauvé S, Gagnon C. Distribution of antidepressant residues in wastewater and biosolids following different treatment processes by municipal wastewater treatment plants in Canada. Water Res. 2012;46(17):5600-12. [Crossref]  [PubMed] 
  8. Kostich MS, Batt AL, Lazorchak JM. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation. Environ Pollut. 2014;184:354-9. [Crossref]  [PubMed] 
  9. González Alonso S, Catalá M, Maroto RR, Gil JL, de Miguel AG, Valcárcel Y. Pollution by psychoactive pharmaceuticals in the Rivers of Madrid metropolitan area (Spain). Environ Int. 2010;36(2):195-201. [Crossref]  [PubMed] 
  10. Oakes KD, Coors A, Escher BI, Fenner K, Garric J, Gust M, et al. Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine: Case study using the European risk assessment framework. Integr Environ Assess Manag. 2010;6 Suppl:524-39. [Crossref]  [PubMed] 
  11. Grzesiuk M, Pawelec A. Fluoxetine results in misleading conclusions on fish behavior. Ecol Evol. 2021;11(14):9707-14. [Crossref]  [PubMed]  [PMC] 
  12. Ansai S, Hosokawa H, Maegawa S, Kinoshita M. Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes. Behav Brain Res. 2016;303:126-36. [Crossref]  [PubMed] 
  13. Campos B, Rivetti C, Kress T, Barata C, Dircksen H. Depressing antidepressant: fluoxetine affects serotonin neurons causing adverse reproductive responses in daphnia magna. Environ Sci Technol. 2016;50(11):6000-7. [Crossref]  [PubMed] 
  14. Minguez L, Farcy E, Ballandonne C, Lepailleur A, Serpentini A, Lebel JM, et al. Acute toxicity of 8 antidepressants: what are their modes of action? Chemosphere. 2014;108:314-9. [Crossref]  [PubMed] 
  15. Flaherty CM, Dodson SI. Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere. 2005;61(2):200-7. [Crossref]  [PubMed] 
  16. Ding J, Zou H, Liu Q, Zhang S, Mamitiana Razanajatovo R. Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna. Ecotoxicol Environ Saf. 2017;142:102-9. [Crossref]  [PubMed] 
  17. Meredith-Williams M, Carter LJ, Fussell R, Raffaelli D, Ashauer R, Boxall AB. Uptake and depuration of pharmaceuticals in aquatic invertebrates. Environ Pollut. 2012;165:250-8. [Crossref]  [PubMed] 
  18. Mesquita SR, Guilhermino L, Guimarães L. Biochemical and locomotor responses of Carcinus maenas exposed to the serotonin reup take inhibitor fluoxetine. Chemosphere. 2011;85(6):967-76. [Crossref]  [PubMed] 
  19. Katzman MA, Jacobs L. Venlafaxine in the treatment of panic disorder. Neuropsychiatr Dis Treat. 2007;3(1):59-67. [Crossref]  [PubMed]  [PMC] 
  20. Ziegler M, Eckstein H, Ottmann S, Reinelt L, Stepinski S, Köhler HR. Biochemical and cellular biomarkers in brown trout (Salmo trutta f. fario) in response to the antidepressants citalopram and venlafaxine. Environ Sci Eur. 2020;32(1):1-15. [Crossref] 
  21. Fernández-Rubio J, Rodríguez-Gil JL, Postigo C, Mastroianni N, López de Alda M, Barceló D, et al. Psychoactive pharmaceuticals and illicit drugs in coastal waters of North-Western Spain: Environmental exposure and risk assessment. Chemosphere. 2019;224:379-89. [Crossref]  [PubMed] 
  22. DrugBank [Internet]. [Cited: ]. Venlafaxine. Available from: [Link] 
  23. Lacaze E, Pédelucq J, Fortier M, Brousseau P, Auffret M, Budzinski H, et al. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes. Environ Pollut. 2015;202:177-86. [Crossref]  [PubMed] 
  24. Sharbaf Shoar N, Fariba KA, Padhy RK. Citalopram. 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. [PubMed] 
  25. Schultz MM, Furlong ET, Kolpin DW, Werner SL, Schoenfuss HL, Barber LB, et al. Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: occurrence and fate in water and sediment, and selective uptake in fish neural tissue. Environ Sci Technol. 2010;44(6):1918-25. [Crossref]  [PubMed] 
  26. Silva LJ, Pereira AM, Meisel LM, Lino CM, Pena A. A one-year follow-up analysis of antidepressants in Portuguese wastewaters: occurrence and fate, seasonal influence, and risk assessment. Sci Total Environ. 2014;490:279-87. [Crossref]  [PubMed] 
  27. Fick J, Söderström H, Lindberg RH, Phan C, Tysklind M, Larsson DG. Contamination of surface, ground, and drinking water from pharmaceutical production. Environ Toxicol Chem. 2009;28(12):2522-7. [Crossref]  [PubMed] 
  28. Martin JM, Saaristo M, Bertram MG, Lewis PJ, Coggan TL, Clarke BO, et al. The psychoactive pollutant fluoxetine compromises antipredator behaviour in fish. Environ Pollut. 2017;222:592-9. [Crossref]  [PubMed] 
  29. Kellner M, Porseryd T, Porsch-Hällström I, Borg B, Roufidou C, Olsén KH. Developmental exposure to the SSRI citalopram causes long-lasting behavioural effects in the three-spined stickleback (Gasterosteus aculeatus). Ecotoxicology. 2018;27(1):12-22. [Crossref]  [PubMed]  [PMC] 
  30. Ziegler M, Knoll S, Köhler HR, Tisler S, Huhn C, Zwiener C, et al. Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout. PeerJ. 2020;8:e8765. [Crossref]  [PubMed]  [PMC] 
  31. Ma LD, Li J, Li JJ, Liu M, Yan DZ, Shi WY, et al. Occurrence and source analysis of selected antidepressants and their metabolites in municipal wastewater and receiving surface water. Environ Sci Process Impacts. 2018;20(7):1020-9. [Crossref]  [PubMed] 
  32. Ziarrusta H, Mijangos L, Izagirre U, Plassmann MM, Benskin JP, Anakabe E, et al. Bioconcentration and Biotransformation of Amitriptyline in Gilt-Head Bream. Environ Sci Technol. 2017;51(4):2464-71. [Crossref]  [PubMed] 
  33. Zenker A, Cicero MR, Prestinaci F, Bottoni P, Carere M. Bioaccumulation and biomagnification potential of pharmaceuticals with a focus to the aquatic environment. J Environ Manage. 2014;133:378-87. [Crossref]  [PubMed] 
  34. Lajeunesse A, Gagnon C, Gagné F, Louis S, Cejka P, Sauvé S. Distribution of antidepressants and their metabolites in brook trout exposed to municipal wastewaters before and after ozone treatment--evidence of biological effects. Chemosphere. 2011;83(4):564-71. [Crossref]  [PubMed] 
  35. Uhr M, Grauer MT, Yassouridis A, Ebinger M. Blood-brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls. J Psychiatr Res. 2007;41(1-2):179-88. [Crossref]  [PubMed] 
  36. Guo W, Hossain MS, Kubec J, Grabicová K, Randák T, Buřič M, et al. Psychoactive compounds at environmental concentration alter burrowing behavior in the freshwater crayfish. Sci Total Environ. 2020;711:135138. [Crossref]  [PubMed] 
  37. Chen H, Liang X, Gu X, Zeng Q, Mao Z, Martyniuk CJ. Environmentally relevant concentrations of sertraline disrupts behavior and the brain and liver transcriptome of juvenile yellow catfish (Tachysurus fulvidraco): Implications for the feeding and growth axis. J Hazard Mater. 2021;409:124974. [Crossref]  [PubMed] 
  38. Mole RA, Brooks BW. Global scanning of selective serotonin reuptake inhibitors: occurrence, wastewater treatment and hazards in aquatic systems. Environ Pollut. 2019;250:1019-31. [Crossref]  [PubMed] 
  39. Styrishave B, Halling-Sørensen B, Ingerslev F. Environmental risk assessment of three selective serotonin reuptake inhibitors in the aquatic environment: a case study including a cocktail scenario. Environ Toxicol Chem. 2011;30(1):254-61. [Crossref]  [PubMed] 
  40. Valenti TW, Gould GG, Berninger JP, Connors KA, Keele NB, Prosser KN, et al. Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows. Environ Sci Technol. 2012;46(4):2427-35. [Crossref]  [PubMed]  [PMC] 
  41. Bossus MC, Guler YZ, Short SJ, Morrison ER, Ford AT. Behavioural and transcriptional changes in the amphipod Echinogammarus marinus exposed to two antidepressants, fluoxetine and sertraline. Aquat Toxicol. 2014;151:46-56. [Crossref]  [PubMed] 
  42. Dorelle LS, Da Cu-a RH, Sganga DE, Rey Vázquez G, López Greco L, Lo Nostro FL. Fluoxetine exposure disrupts food intake and energy storage in the cichlid fish Cichlasoma dimerus (Teleostei, Cichliformes). Chemosphere. 2020;238:124609. [Crossref]  [PubMed] 
  43. Miotto K, Cho AK, Khalil MA, Blanco K, Sasaki JD, Rawson R. Trends in tramadol: pharmacology, metabolism, and misuse. Anesth Analg. 2017;124(1):44-51. [Crossref]  [PubMed] 
  44. Bigal LM, Bibeau K, Dunbar S. Tramadol prescription over a 4-year period in the USA. Curr Pain Headache Rep. 2019;23(10):76. [Crossref]  [PubMed] 
  45. Grabicová K, Grabic R, Fedorova G, Vojs Staňová A, Bláha M, Randák T, et al. Water reuse and aquaculture: Pharmaceutical bioaccumulation by fish during tertiary treatment in a wastewater stabilization pond. Environ Pollut. 2020;267:115593. [Crossref]  [PubMed] 
  46. Bláha M, Grabicova K, Shaliutina O, Kubec J, Randák T, Zlabek V, et al. Foraging behaviour of top predators mediated by pollution of psychoactive pharmaceuticals and effects on ecosystem stability. Sci Total Environ. 2019;662:655-61. [Crossref]  [PubMed] 
  47. Douda K, Zhao S, Vodáková B, Horký P, Grabicová K, Božková K, et al. Host-parasite interaction as a toxicity test endpoint using asymmetrical exposures. Aquat Toxicol. 2019;211:173-80. [Crossref]  [PubMed] 
  48. Sehonova P, Plhalova L, Blahova J, Doubkova V, Prokes M, Tichy F, et al. Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages. Chemosphere. 2017;188:414-23. [Crossref]  [PubMed] 
  49. Santos MES, Horký P, Grabicová K, Hubená P, Slavík O, Grabic R, et al. Traces of tramadol in water impact behaviour in a native European fish. Ecotoxicol Environ Saf. 2021;212:111999. [Crossref]  [PubMed] 
  50. Wawryniuk M, Pietrzak A, Nałęcz-Jawecki G. Evaluation of direct and indirect photodegradation of mianserin with high-performance liquid chromatography and short-term bioassays. Ecotoxicol Environ Saf. 2015;115:144-51. [Crossref]  [PubMed] 
  51. Nałęcz-Jawecki G, Wawryniuk M, Giebułtowicz J, Olkowski A, Drobniewska A. Influence of Selected Antidepressants on the Ciliated Protozoan Spirostomum ambiguum: Toxicity, Bioaccumulation, and Biotransformation Products. Molecules. 2020;25(7):1476. [Crossref]  [PubMed]  [PMC] 

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"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com