Abstract
Hospital wastewater (HWW) contains different hazardous substances resulting from a combination of medical and non-medical activities of hospitals, including pharmaceutical residues. These substances may represent a threat to the aquatic environment if they do not follow specific treatment processes. Therefore, we aimed to investigate the effects of the untreated effluent collected from a general hospital in Mahdia City (Tunisia) on neonatal stages of the freshwater crustacean Daphnia magna. Test organisms were exposed to three proportions (3.12%, 6.25%, and 12.5% v/v) of HWW. After 48 h of exposure, a battery of biomarkers was measured, including the quantification of antioxidant enzymes [catalase (CAT) and total and selenium-dependent glutathione peroxidase (total GPx; Se-GPx)], phase II biotransformation isoenzymes glutathione-S-transferases (GSTs), cyclooxygenases (COX) involved in the regulation of the inflammatory process, and total cholinesterases (ChEs) activities. Lipid peroxidation (LPO) was measured to estimate oxidative damage. The here-obtained results showed significant decreases of CAT and GSTs activities and also on LPO content in daphnids, whereas Se-GPx activity was significantly increased in a dose-dependent manner. Impairment of cholinesterasic and COX activities were also observed, with a significant decrease of ChEs and an increase of COX enzymatic activities. Considering these findings, HWW was capable of inducing an imbalance of the antioxidant defense system, but without resulting in oxidative damage in test organisms, suggesting that peroxidases and alternative detoxifying pathways were able to prevent the oxidant potential of several drugs, which were found in the tested effluents. In general, this study demonstrated the toxicity of hospital effluents, measured in terms of the potential impairment of key pathways, namely neurotransmission, antioxidant defense, and inflammatory homeostasis of crustaceans.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and materials
Data and materials are available.
References
Abe T, Saito H, Niikura Y, Shigeoka T, Nakano Y (2001) Embryonic development assay with Daphnia magna: application to toxicity of aniline derivatives. Chemosphere 45(4–5):487–495. https://doi.org/10.1016/S0045-6535(01)00049-2
Aebi H (1984) Catalase in vitro. Methods Enzymol 6:105–121
Afsa S, Hamden K, Martin PAL, Mansour HB (2020) Occurrence of 40 pharmaceutically active compounds in hospital and urban wastewaters and their contribution to Mahdia coastal seawater contamination. Environ Sci Pollut Res 27(2):1941–1955. https://doi.org/10.1007/s11356-019-06866-5
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. https://doi.org/10.1016/j.ecoenv.2015.09.031
Aguirre-Martínez GV, André C, Gagné F, Martín-Díaz LM (2018) The effects of human drugs in Corbicula fluminea. Assessment of neurotoxicity, inflammation, gametogenic activity, and energy status. Ecotoxicol Environ Saf 148:652–663. https://doi.org/10.1016/j.ecoenv.2017.09.042
Ahmad S (1995) Oxidative stress from environmental pollutants. Arch Insect Biochem Physiol 29(2):135–157. https://doi.org/10.1002/arch.940290205
Alkimin GD, Soares AMVM, Barata C, Nunes B (2020) Evaluation of ketoprofen toxicity in two freshwater species: effects on biochemical, physiological and population endpoints. Environ Pollut 265:114993. https://doi.org/10.1016/j.envpol.2020.114993
Alygizakis NA, Gago-Ferrero P, Borova VL, Pavlidou A, Hatzianestis I, Thomaidis NS (2016) Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater. Sci Total Environ 541:1097–1105. https://doi.org/10.1016/j.scitotenv.2015.09.145
American Society for Testing and Materials, ASTM (1980) Standard practice for conducting acute toxicity tests with fishes, macroinvertebrates and amphibians, Report E-729-80. ASTM, Philadelphia
Artabe AE, Cunha-Silva H, Barranco A (2020) Enzymatic assays for the assessment of toxic effects of halogenated organic contaminants in water and food. A review. Food Chem Toxicol 145:111677. https://doi.org/10.1016/j.fct.2020.111677
American Society for Testing and Materials, ASTM, 1990. Standard Guide for Conducting Daphnia magna Life-Cycle Toxicity Tests. Active Standard ASTM E1193.
Baena-Nogueras RM, Pintado-Herrera MG, González-Mazo E, Lara-Martín PA (2016) Determination of pharmaceuticals in coastal systems using solid phase extraction (SPE) followed by ultra performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS). Curr Anal Chem 12(3):183–201. https://doi.org/10.2174/1573411012666151009193254
Baird DJ, Barber I, Bradley M, Soares AM, Calow P (1991) A comparative study of genotype sensitivity to acute toxic stress using clones of Daphnia magna Straus. Ecotoxicol Environ Saf 21(3):257–265. https://doi.org/10.1016/0147-6513(91)90064-V
Baird DJ, Soares AM, Girling A, Barber I, Bradley MC, Calow P, (1989) The long-term maintenance of Daphnia magna straus. For use in ecotoxicity test problems and prospects. In: Lokke H, Tyle H, Bro-Rasmussen F (Eds.) Proceedings of the First European Conference on Ecotoxicology, pp 144–148
Baldwin WS, LeBlanc GA (1994) In vivo biotransformation of testosterone by phase I and II detoxication enzymes and their modulation by 20-hydroxyecdysone in Daphnia magna. Aquat Toxicol 29(1–2):103–117. https://doi.org/10.1016/0166-445X(94)90051-5
Bamgbose IA, Anderson TA (2018) Assessment of three plant-based biodiesels using a Daphnia magna bioassay. Environ Sci Pollut Res 25(5):4506–4515. https://doi.org/10.1007/s11356-017-0678-7
Barbosa I, Pizarro I, Freitas R, Nunes B (2020) Antioxidative and neurotoxicity effects of acute and chronic exposure of the estuarine polychaete Hediste diversicolor to paracetamol. Environ Toxicol Pharmacol 77:103377. https://doi.org/10.1016/j.etap.2020.103377
Barceló D, Petrovic M (2007) Pharmaceuticals and personal care products (PPCPs) in the environment. Anal Bioanal Chem 387:1141–1142. https://doi.org/10.1007/s00216-006-1012-2
Bebianno MJ, Sroda S, Gomes T, Chan P, Bonnafé E, Budzinski H, Geret F (2016) Proteomic changes in Corbicula fluminea exposed to wastewater from a psychiatric hospital. Environ Sci Pollut Res 23(6):5046–5055. https://doi.org/10.1007/s11356-015-5395-5
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. https://doi.org/10.1016/j.scitotenv.2017.08.279
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5(1):9–19. https://doi.org/10.1097/WOX.0b013e3182439613
Boillot C, Bazin C, Tissot-Guerraz F, Droguet J, Perraud M, Cetre JC, Trepo D, Perrodin Y (2008) Daily physicochemical, microbiological and ecotoxicological fluctuations of a hospital effluent according to technical and care activities. Sci Total Environ 403(1–3):113–129. https://doi.org/10.1016/j.scitotenv.2008.04.037
Bonnafé E, Sroda S, Budzinski H, Valière A, Pedelluc J, Marty P, Geret F (2015) Responses of cytochrome P450, GST, and MXR in the mollusk Corbicula fluminea to the exposure to hospital wastewater effluents. Environ Sci Pollut Res 22(14):11033–11046. https://doi.org/10.1007/s11356-015-4309-x
Bownik A, Pawlik-Skowrońska B (2019) Early indicators of behavioral and physiological disturbances in Daphnia magna (Cladocera) induced by cyanobacterial neurotoxin anatoxin-a. Sci Total Environ 695:133913. https://doi.org/10.1016/j.scitotenv.2019.133913
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(1–2):248–254
Brooks PM, Day RO (1991) Nonsteroidal anti-inflammatory drugs—differences and similarities. N Engl J Med 324(24):1716–1725
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. https://doi.org/10.1016/S0076-6879(78)52032-6
Capolupo M, Valbonesi P, Kiwan A, Buratti S, Franzellitti S, Fabbri E (2016) Use of an integrated biomarker-based strategy to evaluate physiological stress responses induced by environmental concentrations of caffeine in the Mediterranean mussel Mytilus galloprovincialis. Sci Total Environ 563:538–548. https://doi.org/10.1016/j.scitotenv.2016.04.125
Carraro E, Bonetta S, Bertino C, Lorenzi E, Bonetta S, Gilli G (2016) Hospital effluents management: chemical, physical, microbiological risks and legislation in different countries. J Environ Manage 168:185–199. https://doi.org/10.1016/j.jenvman.2015.11.021
Carraro E, Bonetta S, Bonetta S (2017) Hospital wastewater: existing regulations and current trends in management. In: Verlicchi P (ed) Hospital Wastewaters. The Handbook of Environmental Chemistry, vol 60. pp 1–16. https://doi.org/10.1007/698_2017_10
Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605. https://doi.org/10.1152/physrev.1979.59.3.527
Chen KF, Huang SY, Chung YT, Wang KS, Wang CK, Chang SH (2018) Detoxification of nicotine solution using Fe0-based processes: toxicity evaluation by Daphnia magna neonate and embryo assays. Chem Eng J 331:636–643. https://doi.org/10.1016/j.cej.2017.09.029
Cheng L, Chen Y, Zheng YY, Zhan Y, Zhao H, Zhou JL (2017) Bioaccumulation of sulfadiazine and subsequent enzymatic activities in Chinese mitten crab (Eriocheir sinensis). Mar Pollut Bull 121(1–2):176–182. https://doi.org/10.1016/j.marpolbul.2017.06.006
Costantini D (2008) Oxidative stress in ecology and evolution: lessons from avian studies. Ecol Lett 11(11):1238–1251. https://doi.org/10.1111/j.1461-0248.2008.01246.x
Daniel D, Dionísio R, de Alkimin GD, Nunes B (2019) Acute and chronic effects of paracetamol exposure on Daphnia magna: how oxidative effects may modulate responses at distinct levels of organization in a model species. Environ Sci Pollut Res 26(4):3320–3329. https://doi.org/10.1007/s11356-018-3788-y
Davies KJ (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61:1–31. https://doi.org/10.1042/bss0610001
Diamantino TC, Almeida E, Soares AMVM, Guilhermino L (2003) Characterization of cholinesterases from Daphnia magna Straus and their inhibition by zinc. Bull Environ Contam Toxicol 71(2):219–225. https://doi.org/10.1007/s00128-003-0153-7
Ding J, Zou H, Liu Q, Zhang S, Razanajatovo RM (2017) Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna. Ecotoxicol Environ Saf 142:102–109. https://doi.org/10.1016/j.ecoenv.2017.03.042
Dos Santos PRDO, Costa MJ, Dos Santos ACA, Silva-Zacarín EC, Nunes B (2020) Neurotoxic and respiratory effects of human use drugs on a Neotropical fish species, Phalloceros harpagos. Comp Biochem Physiol C: Toxicol Pharmacol 230:108683. https://doi.org/10.1016/j.cbpc.2019.108683
Duarte IA, Reis-Santos P, Novais SC, Rato LD, Lemos MF, Freitas A, Pouca ASV, Barbosa J, Cabral HN, Fonseca VF (2020) Depressed, hypertense and sore: long-term effects of fluoxetine, propranolol and diclofenac exposure in a top predator fish. Sci Total Environ 712:136564. https://doi.org/10.1016/j.scitotenv.2020.136564
Ebele AJ, Abdallah MAE, Harrad S (2017) Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment. Emerging Contaminants 3(1):1–16. https://doi.org/10.1016/j.emcon.2016.12.004
Ek C, Garbaras A, Yu Z, Oskarsson H, Wiklund AKE, Kumblad L, Gorokhova E (2019) Increase in stable isotope ratios driven by metabolic alterations in amphipods exposed to the beta-blocker propranolol. PLoS ONE 14(5):e0211304. https://doi.org/10.1371/journal.pone.0211304
Elia AC, Anastasi V, Dörr AJM (2006) Hepatic antioxidant enzymes and total glutathione of Cyprinus carpio exposed to three disinfectants, chlorine dioxide, sodium hypochlorite and peracetic acid, for superficial water potabilization. Chemosphere 64(10):1633–1641. https://doi.org/10.1016/j.chemosphere.2006.01.035
Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Emmanuel E, Keck G, Blanchard JM, Vermande P, Perrodin Y (2004) Toxicological effects of disinfections using sodium hypochlorite on aquatic organisms and its contribution to AOX formation in hospital wastewater. Environ Int 30(7):891–900. https://doi.org/10.1016/j.envint.2004.02.004
Emmanuel E, Perrodin Y, Keck G, Blanchard JM, Vermande P (2005) Ecotoxicological risk assessment of hospital wastewater: a proposed framework for raw effluents discharging into urban sewer network. J Hazard Mater 117(1):1–11. https://doi.org/10.1016/j.jhazmat.2004.08.032
Environment Canada (1990) Report EPS 1/RM/11. Biological test method: acute lethality test using daphnia species. Environmental Protection Series. Method Development and Applications Section. Environmental Technology Centre
Escudero-Oñate C, Ferrando-Climent L, Rodríguez-Mozaz S, Santos LH (2017) Occurrence and risks of contrast agents, cytostatics, and antibiotics in hospital effluents. In: Verlicchi P (ed) Hospital Wastewaters. The Handbook of Environmental Chemistry, vol 60. Springer, Cham, pp 71–100. https://doi.org/10.1007/698_2017_12
Fekadu S, Alemayehu E, Dewil R, Van der Bruggen B (2019) Pharmaceuticals in freshwater aquatic environments: a comparison of the African and European challenge. Sci Total Environ 654:324–337. https://doi.org/10.1016/j.scitotenv.2018.11.072
Fent K, Weston AA, Caminada D (2006) Ecotoxicology of human pharmaceuticals. Aquatic Toxicology 76(2):122–159. https://doi.org/10.1016/j.aquatox.2005.09.009
Fink RC, Scandalios JG (2002) Molecular evolution and structure–function relationships of the superoxide dismutase gene families in angiosperms and their relationship to other eukaryotic and prokaryotic superoxide dismutases. Arch Biochem Biophys 399(1):19–36. https://doi.org/10.1006/abbi.2001.2739
Flohé L, Günzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–120. https://doi.org/10.1016/S0076-6879(84)05015-1
Freitas R, Silvestro S, Coppola F, Meucci V, Battaglia F, Intorre L, Soares AM, Pretti C, Faggio C (2019) Biochemical and physiological responses induced in Mytilus galloprovincialis after a chronic exposure to salicylic acid. Aquat Toxicol 214:105258. https://doi.org/10.1016/j.aquatox.2019.105258
Gagné F, Blaise C, André C, Gagnon C, Salazar M (2007) Neuroendocrine disruption and health effects in Elliptio complanata mussels exposed to aeration lagoons for wastewater treatment. Chemosphere 68(4):731–743. https://doi.org/10.1016/j.chemosphere.2006.12.101
Gagnon C, Lajeunesse A (2008) Persistence and fate of highly soluble pharmaceutical products in various types of municipal wastewater treatment plants. WIT Trans Ecol Environ 109:799–807. https://doi.org/10.2495/WM080811
Gašo-Sokač D, Habuda-Stanić M, Bušić V, Zobundžija D (2017) Occurrence of pharmaceuticals in surface water. Croatian J Food Sci Technol 9(2):204–210. https://doi.org/10.17508/CJFST.2017.9.2.18
Geissen V, Mol H, Klumpp E, Umlauf G, Nadal M, van der Ploeg M, van de Zee SEATM, Ritsema CJ (2015) Emerging pollutants in the environment: a challenge for water resource management. Int Soil Water Conserv Res 3(1):57–65. https://doi.org/10.1016/j.iswcr.2015.03.002
Gheorghe S, Mitroi DN, Stan MS, Staicu CA, Cicirma M, Lucaciu IE, Nita-Lazar M, Dinischiotu A (2020) Evaluation of sub-lethal toxicity of benzethonium chloride in Cyprinus carpio liver. Appl Sci 10(23):8485. https://doi.org/10.3390/app10238485
Giraudo M, Colson TL, Pilote M, Gagnon C, Gagnon P, Houde M (2019) A major release of urban untreated wastewaters in the St. Lawrence River (Quebec, Canada) altered growth, reproduction, and redox status in experimentally exposed Daphnia magna. Ecotoxicology 28(7):843–851. https://doi.org/10.1007/s10646-019-02084-4
Gómez MJ, Petrović M, Fernández-Alba AR, Barceló D (2006) Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography–tandem mass spectrometry analysis in hospital effluent wastewaters. J Chromatogr A 1114(2):224–233. https://doi.org/10.1016/j.chroma.2006.02.038
Gómez-Oliván LM, Galar-Martínez M, Islas-Flores H, García-Medina S, SanJuan-Reyes N (2014) DNA damage and oxidative stress induced by acetylsalicylic acid in Daphnia magna. Comp Biochem Physiol C: Toxicol Pharmacol 164:21–26. https://doi.org/10.1016/j.cbpc.2014.04.004
Green J (1957) Carotenoids in Daphnia. Proceedings of the Royal Society of London. Series B-Biol Sci 147(928):392–401. https://doi.org/10.1098/rspb.1957.0058
Gust M, Fortier M, Garric J, Fournier M, Gagné F (2013) Effects of short-term exposure to environmentally relevant concentrations of different pharmaceutical mixtures on the immune response of the pond snail Lymnaea stagnalis. Sci Total Environ 445:210–218. https://doi.org/10.1016/j.scitotenv.2012.12.057
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139. https://doi.org/10.1016/S0021-9258(19)42083-8
Heckmann LH, Sibly RM, Timmermans MJ, Callaghan A (2008) Outlining eicosanoid biosynthesis in the crustacean Daphnia. Front Zool 5(1):1–9. https://doi.org/10.1186/1742-9994-5-11
Hindák F (1990) International Symposium “Biology and Taxonomy of Green Algae”, Smolenice, Czecho-slovakia, June. pp. 25–29 report. https://doi.org/10.1016/S0003-9365(11)80002-3
Ikenaka Y, Eun H, Ishizaka M, Miyabara Y (2006) Metabolism of pyrene by aquatic crustacean, Daphnia magna. Aquatic Toxicol 80(2):158–165. https://doi.org/10.1016/j.aquatox.2006.08.005
JORT (Journal Officiel de la République Tunisienne), no 26, page 822. Ministère des affaires locales et de l’environnement et de l’industrie et des petites et moyennes entreprises, Arrêté du 26 mars 2018 fixant les valeurs limites des rejets d’effluents dans le milieu récepteur.
Kavitha P, Ramesh R, Bupesh G, Stalin A, Subramanian P (2011) Hepatoprotective activity of Tribulus terrestris extract against acetaminophen-induced toxicity in a freshwater fish (Oreochromis mossambicus). In Vitro Cell Dev Biol Animal 47(10):698–706. https://doi.org/10.1007/s11626-011-9457-9
Koivisto S (1995) Is Daphnia magna an ecologically representative zooplankton species in toxicity tests? Environ Pollut 90(2):263–267. https://doi.org/10.1016/0269-7491(95)00029-Q
Kukkonen J, Oikari A (1988) Sulphate conjugation is the main route of pentachlorophenol metabolism in Daphnia magna. Comp Biochem Physiol Part C: Comp Pharmacol 91(2):465–468. https://doi.org/10.1016/0742-8413(88)90060-6
Kümmerer K (2004) Pharmaceuticals in the environment — scope of the book and introduction. In: Kümmerer K (ed) Pharmaceuticals in the Environment Sources, Fate, Effects and Risks. Springer, Berlin, pp 3–11. https://doi.org/10.1007/978-3-662-09259-0_1
Leprat P (1998) Les rejets liquides hospitaliers, quels agents et quelles solutions techniques. Revue Techniques Hospitalieres 632:49–52
Li MH (2008) Effects of nonionic and ionic surfactants on survival, oxidative stress, and cholinesterase activity of planarian. Chemosphere 70(10):1796–1803. https://doi.org/10.1016/j.chemosphere.2007.08.032
Li Z, Lu G, Yang X, Wang C (2012) Single and combined effects of selected pharmaceuticals at sublethal concentrations on multiple biomarkers in Carassius auratus. Ecotoxicology 21(2):353–361. https://doi.org/10.1007/s10646-011-0796-9
Lin T, Yu S, Chen Y, Chen W (2014) Integrated biomarker responses in zebrafish exposed to sulfonamides. Environ Toxicol Pharmacol 38(2):444–452. https://doi.org/10.1016/j.etap.2014.07.020
Liu J, Wei T, Wu X, Zhong H, Qiu W, Zheng Y (2020) Early exposure to environmental levels of sulfamethoxazole triggers immune and inflammatory response of healthy zebrafish larvae. Sci Total Environ 703:134724. https://doi.org/10.1016/j.scitotenv.2019.134724
Maranho LA, Baena-Nogueras RM, Lara-Martín PA, DelValls TA, Martín-Díaz ML (2014) Bioavailability, oxidative stress, neurotoxicity and genotoxicity of pharmaceuticals bound to marine sediments. The use of the polychaete Hediste diversicolor as bioindicator species. Environ Res 134:353–365. https://doi.org/10.1016/j.envres.2014.08.014
Martínez G, Rivera A (1994) Role of monoamines in the reproductive process of Argopecten pupuratus. Invertebr Reprod Dev 25(2):167–174. https://doi.org/10.1080/07924259.1994.9672381
Mendoza A, Aceña J, Pérez S, De Alda ML, Barceló D, Gil A, Valcárcel Y (2015) Pharmaceuticals and iodinated contrast media in a hospital wastewater: a case study to analyse their presence and characterise their environmental risk and hazard. Environ Res 140:225–241. https://doi.org/10.1016/j.envres.2015.04.003
Mennillo E, Krøkje Å, Pretti C, Meucci V, Arukwe A (2018) Biotransformation and oxidative stress responses in rat hepatic cell-line (H4IIE) exposed to racemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S (+)-KP). Environ Toxicol Pharmacol 59:199–207. https://doi.org/10.1016/j.etap.2018.03.018
Miner BE, De Meester L, Pfrender ME, Lampert W, Hairston NG Jr (2012) Linking genes to communities and ecosystems: Daphnia as an ecogenomic model. Proc Royal Soc B: Biol Sci 279(1735):1873–1882. https://doi.org/10.1098/rspb.2011.2404
Moller AP, Biard C, Blount JD, Houston DC, Ninni P, Saino N, Surai PF (2000) Carotenoid-dependent signals: indicators of foraging efficiency, immunocompetence or detoxification ability? Poultry Avian Biol Rev 11(3):137–160
Neri-Cruz N, Gómez-Oliván LM, Galar-Martínez M, del Socorro Romero-Figueroa M, Islas-Flores H, García-Medina S, Jiménez-Vargas JM, SanJuan-Reyes N (2015) Oxidative stress in Cyprinus carpio induced by hospital wastewater in Mexico. Ecotoxicology 24(1):181–193. https://doi.org/10.1007/s10646-014-1371-y
Nikolaou A, Meric S, Fatta D (2007) Occurrence patterns of pharmaceuticals in water and wastewater environments. Anal Bioanal Chem 387(4):1225–1234. https://doi.org/10.1007/s00216-006-1035-8
Nkoom M, Lu G, Liu J, Yang H, Dong H (2019) Bioconcentration of the antiepileptic drug carbamazepine and its physiological and biochemical effects on Daphnia magna. Ecotoxicol Environ Saf 172:11–18. https://doi.org/10.1016/j.ecoenv.2019.01.061
Nogueira AF, Nunes B (2021) Effects of paracetamol on the polychaete Hediste diversicolor: occurrence of oxidative stress, cyclooxygenase inhibition and behavioural alterations. Environ Sci Pollut Res 28:1–12. https://doi.org/10.1007/s11356-020-12046-7
Nunes B (2011) The use of cholinesterases in ecotoxicology. Rev Environ Contam Toxicol 212:29–59. https://doi.org/10.1007/978-1-4419-8453-1_2
Nunes B (2019) Acute ecotoxicological effects of salicylic acid on the Polychaeta species Hediste diversicolor: evidences of low to moderate pro-oxidative effects. Environ Sci Pollut Res 26(8):7873–7882. https://doi.org/10.1007/s11356-018-04085-y
Nunes B, Carvalho F, Guilhermino L (2006) Effects of widely used pharmaceuticals and a detergent on oxidative stress biomarkers of the crustacean Artemia parthenogenetica. Chemosphere 62(4):581–594. https://doi.org/10.1016/j.chemosphere.2005.06.013
Nunes B, Gaio AR, Carvalho F, Guilhermino L (2008) Behaviour and biomarkers of oxidative stress in Gambusia holbrooki after acute exposure to widely used pharmaceuticals and a detergent. Ecotoxicol Environ Saf 71(2):341–354. https://doi.org/10.1016/j.ecoenv.2007.12.006
Nunes B, Antunes SC, Santos J, Martins L, Castro BB (2014) Toxic potential of paracetamol to freshwater organisms: a headache to environmental regulators? Ecotoxicol Environ Saf 107:178–185. https://doi.org/10.1016/j.ecoenv.2014.05.027
Nunes B, Campos JC, Gomes R, Braga MR, Ramos AS, Antunes SC, Correia AT (2015a) Ecotoxicological effects of salicylic acid in the freshwater fish Salmo trutta fario: antioxidant mechanisms and histological alterations. Environ Sci Pollut Res 22(1):667–678. https://doi.org/10.1007/s11356-014-3337-2
Nunes B, Verde MF, Soares AM (2015b) Biochemical effects of the pharmaceutical drug paracetamol on Anguilla anguilla. Environ Sci Pollut Res 22(15):11574–11584. https://doi.org/10.1007/s11356-015-4329-6
Nunes B, Daniel D, Canelas GG, Barros J, Correia AT (2020) Toxic effects of environmentally realistic concentrations of diclofenac in organisms from two distinct trophic levels, Hediste diversicolor and Solea senegalensis. Comp Biochem Physiol C: Toxicol Pharmacol 231:108722. https://doi.org/10.1016/j.cbpc.2020.108722
Oboh G, Ogunsuyi OB, Olonisola OE (2017) Does caffeine influence the anticholinesterase and antioxidant properties of donepezil? Evidence from in vitro and in vivo studies. Metab Brain Dis 32(2):629–639. https://doi.org/10.1007/s11011-017-9951-1
Oliveira TS, Murphy M, Mendola N, Wong V, Carlson D, Waring L (2015a) Characterization of pharmaceuticals and personal care products in hospital effluent and waste water influent/effluent by direct-injection LC-MS-MS. Sci Total Environ 518:459–478. https://doi.org/10.1016/j.scitotenv.2015.02.104
Oliveira LL, Antunes SC, Gonçalves F, Rocha O, Nunes B (2015b) Evaluation of ecotoxicological effects of drugs on Daphnia magna using different enzymatic biomarkers. Ecotoxicol Environ Saf 119:123–131. https://doi.org/10.1016/j.ecoenv.2015.04.028
Olvera-Néstor CG, Morales-Avila E, Gómez-Olivan LM, Galár-Martínez M, García-Medina S, Neri-Cruz N (2016) Biomarkers of cytotoxic, genotoxic and apoptotic effects in Cyprinus carpio exposed to complex mixture of contaminants from hospital effluents. Bull Environ Contam Toxicol 96(3):326–332. https://doi.org/10.1007/s00128-015-1721-3
Organisation for economic co-operation and development, OECD (2004) OECD Guideline for Testing of Chemicals 202. Daphnia sp., Acute Immobilization Test
Oropesa AL, Novais SC, Lemos MF, Espejo A, Gravato C, Beltrán F (2017) Oxidative stress responses of Daphnia magna exposed to effluents spiked with emerging contaminants under ozonation and advanced oxidation processes. Environ Sci Pollut Res 24(2):1735–1747. https://doi.org/10.1007/s11356-016-7881-9
Pereira BV, Matus GN, Costa MJ, Dos Santos ACA, Silva-Zacarin EC, do Carmo, J.B. and Nunes, B. (2018) Assessment of biochemical alterations in the neotropical fish species Phalloceros harpagos after acute and chronic exposure to the drugs paracetamol and propranolol. Environ Sci Pollut Res 25(15):14899–14910. https://doi.org/10.1007/s11356-018-1699-6
Pérez-Alvarez I, Islas-Flores H, Gómez-Oliván LM, Barceló D, De Alda ML, Solsona SP, Sánchez-Aceves L, SanJuan-Reyes N, Galar-Martínez M (2018) Determination of metals and pharmaceutical compounds released in hospital wastewater from Toluca, Mexico, and evaluation of their toxic impact. Environ Pollut 240:330–341. https://doi.org/10.1016/j.envpol.2018.04.116
Petrovic N, Murray M (2010) Using N, N, N’, N’-tetramethyl-p-phenylenediamine (TMPD) to assay cyclooxygenase activity in vitro. In: Armstrong D (ed) Advanced Protocols in Oxidative Stress II. Methods in Molecular Biology (Methods and Protocols), vol 594. Humana Press, Totowa. https://doi.org/10.1007/978-1-60761-411-1_9
Picado A, Chankova S, Fernandes A, Simões F, Leverett D, Johnson I, Hernan R, Pires AM, Matos J (2007) Genetic variability in Daphnia magna and ecotoxicological evaluation. Ecotoxicol Environ Saf 67(3):406–410. https://doi.org/10.1016/j.ecoenv.2006.10.004
Pires A, Almeida Â, Calisto V, Schneider RJ, Esteves VI, Wrona FJ, Soares AM, Figueira E, Freitas R (2016) Long-term exposure of polychaetes to caffeine: biochemical alterations induced in Diopatra neapolitana and Arenicola marina. Environ Pollut 214:456–463. https://doi.org/10.1016/j.envpol.2016.04.031
Pohanka M, Dobes P (2013) Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase. Int J Mol Sci 14(5):9873–9882. https://doi.org/10.3390/2Fijms14059873
Pôrto WG (2001) Free radicals and neurodegeneration. Physiological understanding: basis for new therapy? Rev Neurosci 9(2):70–76
Rhee JS, Kim BM, Jeong CB, Park HG, Leung KMY, Lee YM, Lee JS (2013) Effect of pharmaceuticals exposure on acetylcholinesterase (AchE) activity and on the expression of AchE gene in the monogonont rotifer, Brachionus koreanus. Comp Biochem Physiol C: Toxicol Pharmacol 158(4):216–224. https://doi.org/10.1016/j.cbpc.2013.08.005
Rocha R, Gonçalves F, Marques C, Nunes B (2014) Environmental effects of anticholinesterasic therapeutic drugs on a crustacean species, Daphnia magna. Environ Sci Pollut Res 21(6):4418–4429. https://doi.org/10.1007/s11356-013-2339-9
Ruotsalainen AM, Akkanen J, Kukkonen JV (2010) Dissolved organic matter modulating the uptake, biotransformation, and elimination rates of pyrene in Daphnia magna. Environ Toxicol Chem 29(12):2783–2791. https://doi.org/10.1002/etc.335
Sahu VK, Karmakar S, Kumar S, Shukla SP, Kumar K (2018) Triclosan toxicity alters behavioral and hematological parameters and vital antioxidant and neurological enzymes in Pangasianodon hypophthalmus (Sauvage, 1878). Aquat Toxicol 202:145–152. https://doi.org/10.1016/j.aquatox.2018.07.009
Santos LH, Gros M, Rodriguez-Mozaz S, Delerue-Matos C, Pena A, Barceló D, Montenegro MCB (2013) Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals. Sci Total Environ 461:302–316. https://doi.org/10.1016/j.scitotenv.2013.04.077
Santos-Silva TG, Montagner CC, Martinez CB (2018) Evaluation of caffeine effects on biochemical and genotoxic biomarkers in the neotropical freshwater teleost Prochilodus lineatus. Environ Toxicol Pharmacol 58:237–242. https://doi.org/10.1016/j.etap.2018.02.002
Smirnov NN (2017) Physiology of the Cladocera, 2nd edn. Elsevier, Amsterdam, p 806
Smith LS (2006) Factors influencing glutathione S-transferases in Daphnia magna (Doctoral dissertation, University of Maryland, College Park).
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(2):649–656. https://doi.org/10.1007/s00216-009-3182-1
Sörengård M, Campos-Pereira H, Ullberg M, Lai FY, Golovko O, Ahrens L (2019) Mass loads, source apportionment, and risk estimation of organic micropollutants from hospital and municipal wastewater in recipient catchments. Chemosphere 234:931–941. https://doi.org/10.1016/j.chemosphere.2019.06.041
Stein JR (1973) Handbook of phycological methods: culture methods and growth measurements. Cambridge University Press, London, pp 7–24
Tahrani L, Van Loco J, Anthonissen R, Verschaeve L, Ben Mansour H, Reyns T (2017) Identification and risk assessment of human and veterinary antibiotics in the wastewater treatment plants and the adjacent sea in Tunisia. Water Sci Technol 76(11):3000–3021. https://doi.org/10.2166/wst.2017.465
Tan K, Zhang H, Lim LS, Ma H, Li S, Zheng H (2020) Roles of carotenoids in invertebrate immunology. Front Immunol 10:3041. https://doi.org/10.3389/fimmu.2019.03041
Tian X, Song E, Pi R, Zhu X, Liu L, Ma X, Dong H, Liu J, Song Y (2012) Polychlorinated biphenyls and their different level metabolites as inhibitors of glutathione S-transferase isoenzymes. Chem Biol Interact 198(1–3):1–8. https://doi.org/10.1016/j.cbi.2012.04.002
Tkachenko H, Kurhaluk N, Grudniewska J (2015) Biomarkers of oxidative stress and antioxidant defences as indicators of different disinfectants exposure in the heart of rainbow trout (Oncorhynchus mykiss Walbaum). Aquac Res 46(3):679–689. https://doi.org/10.1111/are.12214
Tkaczyk A, Bownik A, Dudka J, Kowal K, Ślaska B (2020) Daphnia magna model in the toxicity assessment of pharmaceuticals: a review. Sci Total Environ 763:143038. https://doi.org/10.1016/j.scitotenv.2020.143038
Ton SS, Chang SH, Hsu LY, Wang MH, Wang KS (2012) Evaluation of acute toxicity and teratogenic effects of disinfectants by Daphnia magna embryo assay. Environ Pollut 168:54–61. https://doi.org/10.1016/j.envpol.2012.04.008
Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552(2):335–344. https://doi.org/10.1111/j.1469-7793.2003.00335.x
US EPA (1996) Ecological Effects Test Guidelines OPPTS 850.1300. Daphnid Chronic Toxicity Test. United States Environmental Protection Agency Prevention, Pesticides and Toxic Substances (7101), EPA 712–C–96–120.
US EPA (1998) US Environmental Protection Agency. SCE policy issues related to the food quality protection act. Office of pesticide programs science policy on the use of cholinesterase inhibition for risk assessment of organophosphate and carbamate pesticides. OOP Docket # 00560. Federal register, 63, p. 214
Van Ommen B, Ploemen JHTM, Bogaards JJP, Monks TJ, Gau SS, Van Bladeren PJ (1991) Irreversible inhibition of rat glutathione S-transferase 1–1 by quinones and their glutathione conjugates. Struct Activ Relat Mechan Biochem J 276(3):661–666
Vasseur P, Leguille C (2004) Defense systems of benthic invertebrates in response to environmental stressors. Environ Toxicol 19(4):433–436. https://doi.org/10.1002/tox.20024
Verlicchi P, Galletti A, Petrovic M, Barceló D (2010) Hospital effluents as a source of emerging pollutants: an overview of micropollutants and sustainable treatment options. J Hydrol 389(3–4):416–428. https://doi.org/10.1016/j.jhydrol.2010.06.005
Verlicchi P, Al Aukidy M, Galletti A, Petrovic M, Barceló D (2012) Hospital effluent: investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment. Sci Total Environ 430:109–118. https://doi.org/10.1016/j.scitotenv.2012.04.055
Wang KS, Lu CY, Chang SH (2011) Evaluation of acute toxicity and teratogenic effects of plant growth regulators by Daphnia magna embryo assay. J Hazard Mater 190(1–3):520–528. https://doi.org/10.1016/j.jhazmat.2011.03.068
Yang HB, Zhao YZ, Tang Y, Gong HQ, Guo F, Sun WH, Liu SS, Tan H, Chen F (2019) Antioxidant defence system is responsible for the toxicological interactions of mixtures: a case study on PFOS and PFOA in Daphnia magna. Sci Total Environ 667:435–443. https://doi.org/10.1016/j.scitotenv.2019.02.418
Zivna D, Sehonova P, Plhalova L, Marsalek P, Blahova J, Prokes M, Divisova L, Stancova V, Dobsikova R, Tichy F, Siroka Z (2015) Effect of salicylic acid on early life stages of common carp (Cyprinus carpio). Environ Toxicol Pharmacol 40(1):319–325. https://doi.org/10.1016/j.etap.2015.06.018
Zivna D, Blahova J, Siroka Z, Plhalova L, Marsalek P, Doubkova V, Zelinska G, Vecerek V, Tichy F, Sehonova P, Svobodova Z (2016) The effects of salicylic acid on juvenile zebrafish Danio rerio under flow-through conditions. Bull Environ Contam Toxicol 97(3):323–330. https://doi.org/10.1007/s00128-016-1877-5
Funding
This research was funded by Fundação para a Ciência e a Tecnologia, FCT (project ECO-R-pharmplast – Ecotoxicity of realistic combinations of pharmaceutical drugs and microplastics in marine ecosystems, reference POCI-01–0145-FEDER-029203). FCT also funded the research center CESAM, in which the research was conducted (UIDB/50017/2020 + UIDP/50017/2020); CESAM was also co-funded by ERDF, within the PT2020 Partnership Agreement and Compete 2020. This research was also funded by the Ministry of Higher Education and Scientific Research in Tunisia. None of these sources of funding had any role in the design of the study and collection, analysis, and interpretation of data and in the writing of the manuscript.
Author information
Authors and Affiliations
Contributions
All authors contributed to this work.
Sabrine Afsa: conceptualization, visualization, methodology, formal analysis, data curation, writing – original draft.
Madalena Vieira: methodology; formal analysis; software; data curation.
Ana Filipa Nogueira: methodology, formal analysis.
Hedi ben Mansour: supervision, review and editing.
Bruno Nunes: supervision, validation, writing – review and editing.
Corresponding author
Ethics declarations
Ethics approval
Authors commit to upholding the integrity of the scientific according to the COPE guidelines. Authors declare refrain from misrepresenting research results, which could damage the trust in the journal.
Consent to participate
This work was carried out in collaboration between all authors. All authors read and approved the final manuscript.
Consent for publication
The authors declare that there is no conflict of interest regarding the publication of this paper.
Conflict of interest
The authors declare no competing interests.
Additional information
Responsible Editor: Philippe Garrigues
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Afsa, S., Vieira, M., Nogueira, A. et al. A multi-biomarker approach for the early assessment of the toxicity of hospital wastewater using the freshwater organism Daphnia magna. Environ Sci Pollut Res 29, 19132–19147 (2022). https://doi.org/10.1007/s11356-021-16977-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-021-16977-7