Environmental Science and Pollution Research

, Volume 25, Issue 28, pp 28601–28618 | Cite as

Behavior and histopathology as biomarkers for evaluation of the effects of paracetamol and propranolol in the neotropical fish species Phalloceros harpagos

  • Gregorio Nolazco Matus
  • Beatriz V. R. Pereira
  • Elaine C. M. Silva-Zacarin
  • Monica Jones Costa
  • André Cordeiro Alves dos Santos
  • Bruno NunesEmail author
Research Article


Pharmaceutical drugs in the aquatic environment can induce adverse effects on nontarget organisms. This study aimed to assess the short-term effects of sublethal concentrations of both paracetamol and propranolol on the fish Phalloceros harpagos, specifically light/dark preference, swimming patterns, skin pigmentation, histopathology, and liver glycogen levels. Fish were acutely exposed to sublethal concentrations of both paracetamol (0.008, 0.08, 0.8, 8, 80 mg L−1) and propranolol (0.0001, 0.001, 0.01, 0.1, 1 mg L−1) under controlled conditions. For scototaxis, a significant preference for the dark compartment was observed for the group exposed to the highest concentration of paracetamol (80 mg L−1). Propranolol exposure significantly altered the swimming pattern, especially in fish exposed to the 0.001 mg L−1 concentration. Pigmentation was reduced in propranolol-exposed fish (0.1, 1 mg L−1). The lowest concentration of propranolol (0.0001 mg L−1) induced a decrease of histochemical reaction for hepatic glycogen. These data demonstrate that pharmaceuticals can induce sublethal effects in nontarget organisms, even at low concentrations, compromising specific functions of the individual with ecological relevance, such as energy balance and behavior.


Guaru Pharmaceuticals Tropical areas Freshwater Liver histopathology Hepatic glycogen Acute toxicity 



We thank the LAMA from the Department of Biology in UFSCar for the infrastructural support for bioassays and Osmar Malaspina from UNESP/Rio Claro for infrastructural support in relation to microtomy of fish livers for histological analysis.

Funding information

Bruno Nunes was hired under the program Investigador FCT, co-funded by the Human Potential Operational Program (National Strategic Reference Framework 2007–2013) and European Social Fund (EU). Thanks are due to the program Pesquisador Visitante Especial, financed by Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, with the project entitled “Avaliação dos efeitos ecotoxicológicos de drogas terapêuticas com relevância ambiental em espécies de peixes autóctones brasileiros: uso de biomarcadores de stress oxidativo” (2014–2017).

Supplementary material

11356_2018_2839_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)
11356_2018_2839_MOESM2_ESM.docx (37 kb)
ESM 2 (DOCX 36 kb)
11356_2018_2839_MOESM3_ESM.docx (14 kb)
ESM 3 (DOCX 13 kb)


  1. Agbohessi PT, Toko II, Ouédraogo A, Jauniaux T, Mandiki SNM, Kestemont P (2015) Assessment of the health status of wild fish inhabiting a cotton basin heavily impacted by pesticides in Benin (West Africa). Sci Total Environ 506:567–584CrossRefGoogle Scholar
  2. Ahles A, Engelhardt S (2014) Polymorphic variants of adrenoceptors: pharmacology, physiology, and role in disease. Pharmacol Rev 66(3):598–637CrossRefGoogle Scholar
  3. Ahmed MB, Zhou JL, Ngo HH, Guo W, Thomaidis NS, Xu J (2017) Progress in the biological and chemical treatment technologies for emerging contaminant removal from wastewater: a critical review. J Hazard Mater 323:274–298CrossRefGoogle Scholar
  4. Akiyoshi H, Inoue A (2004) Comparative histological study of teleost livers in relation to phylogeny. Zoological science 21(8):841–850CrossRefGoogle Scholar
  5. Akiyoshi H, Inoue A, Hamana A (2001) Comparative histochemical study of the livers of marine fishes in relation to their behavior. Bulletin of the Faculty of Life and Environmental Science-Shimane University (Japan)Google Scholar
  6. Alamgeer ZN, Muhammad NQ, Ambreen MU, Haseeb A, Kifayat UK, Ikram UK, Muhamamd S, Khadija HA, Amber S, Waqas Y, Huma N (2017) Evaluation of hepatoprotective activity of Melilotus officianalis L. against paracetamol and carbon tetrachloride induced hepatic injury in mice. Acta Pol Pharm Drug Res 74(3):903–909Google Scholar
  7. Alexander BS, Wood MD (1987) Stereoselective blockade of central [3H] 5-hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B, and 5-HT1C) by mianserin and propranolol. J Pharm Pharmacol 39:664–666CrossRefGoogle Scholar
  8. Al-Majed AA, Bakheit AH, Aziz HAA, Alajmi FM, AlRabiah H (2017) Propranolol. In Profiles of Drug Substances, Excipients and Related Methodology 42:287–338Google Scholar
  9. Altimiras J, Aissaoui A, Torte L (1995) Is the short-term modulation of heart rate in teleost fish physiologically significant? Assessment by spectral analysis techniques. Braz J Med Biol Res 28(11–12):1197–1206Google Scholar
  10. Andreozzi R, Raffaele M, Nicklas P (2003) Pharmaceuticals in STP effluents and their solar photodegradation in aquatic environment. Chemosphere 50(10):1319–1330CrossRefGoogle Scholar
  11. Aranha JMR, Caramaschi EP (1999) Estrutura populacional, aspectos da reprodução e alimentação dos Cyprinodontiformes (Osteichthyes) de um riacho do sudeste do Brasil. Revista - Sociedade Brasilieira de Zootecnia 16:637–651 CrossRefGoogle Scholar
  12. Ashton D, Hilton M, Thomas KV (2004) Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom. Sci Total Environ 333:167–184CrossRefGoogle Scholar
  13. Backström T, Brännäs E, Nilsson J, Magnhagen C (2014) Behaviour, physiology and carotenoid pigmentation in Arctic charr Salvelinus alpinus. J Fish Biol 84(1):1–9CrossRefGoogle Scholar
  14. Bain PA, Kumar A (2014) Cytotoxicity of binary mixtures of human pharmaceuticals in a fish cell line: approaches for non-monotonic concentration–response relationships. Chemosphere 108:334–342CrossRefGoogle Scholar
  15. Bernet D, Schmidt H, Meier W, Burkhardt-holm P, Wahli T (1999) Histopathology in fish: proposal for a protocol to assess aquatic pollution. J Fish Dis 22:25–34CrossRefGoogle Scholar
  16. Birch GF, Drage DS, Thompson K, Eaglesham G, Mueller JF (2015) Emerging contaminants (pharmaceuticals, personal care products, a food additive and pesticides) in waters of Sydney estuary, Australia. Mar Pollut Bull 97(1–2):56–66CrossRefGoogle Scholar
  17. Brandão FP, Rodrigues S, Castro BB, Goncalves F, Antunes SC, Nunes B (2013) Short-term effects of neuroactive pharmaceutical drugs on a fish species: biochemical and behavioural effects. Aquat Toxicol 144:218–229CrossRefGoogle Scholar
  18. Burton D (2002) The physiology of flatfish chromatophores. Microsc Res Tech 58(6):481–487CrossRefGoogle Scholar
  19. Calabrese EJ (2008) Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 27(7):1451–1474CrossRefGoogle Scholar
  20. Campanha MC, Awan AT, De Sousa DN, Grosseli GM, Mozeto AA, Fadini PS (2015) A 3-year study on occurrence of emerging contaminants in an urban stream of São Paulo State of southeast Brazil. Environ Sci Pollut Res 22(10):7936–7947CrossRefGoogle Scholar
  21. Chaouchi S, Hamdaoui O (2014) Acetaminophen extraction by emulsion liquid membrane using Aliquat 336 as extractant. Sep Purif Technol 129:32–40CrossRefGoogle Scholar
  22. Chaouloff F (1993) Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev 18:1–32CrossRefGoogle Scholar
  23. Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142:185–194CrossRefGoogle Scholar
  24. Cleuvers M (2005) Initial risk assessment for three β-blockers found in the aquatic environment. Chemosphere 59(2):199–205CrossRefGoogle Scholar
  25. Coetsier CM, Spinelli S, Lin L, Roig B, Touraud E (2009) Discharge of pharmaceutical products (PPs) through a conventional biological sewage treatment plant: MECs vs PECs? Environ Int 35:787–792CrossRefGoogle Scholar
  26. Crespel A, Dupont-prinet A, Bernatchez L, Claireaux G, Tremblay R, Audet C (2017) Divergence in physiological factors affecting swimming performance between anadromous and resident populations of brook charr Salvelinus fontinalis. J Fish Biol 90(5):2170–2193CrossRefGoogle Scholar
  27. Cruz C, Fujimoto RY, Luz RK, Portella MC, Laterça M (2005) Toxicidade aguda e histopatologia do fígado de larvas de trairão (Hoplias lacerdae) expostas à solução aquosa de formaldeído a 10%. Pesticidas: Revista de ecotoxicologia e meio ambiente 15:21–28Google Scholar
  28. Danulat E, Mommsen TP (1990) Norepinephrine: a potent activator of glycogenolysis and gluconeogenesis in rockfish hepatocytes. Gen Comp Endocrinol 78(1):12–22CrossRefGoogle Scholar
  29. Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 107:907–938CrossRefGoogle Scholar
  30. David A, Pancharatna K (2009) Effects of acetaminophen (paracetamol) in the embryonic development of zebrafish, Danio rerio. J Appl Toxicol 29(7):597–602CrossRefGoogle Scholar
  31. de Voogt P, Janex-habibi ML, Sacher F, Puijker L, Mons M (2009) Development of a common priority list of pharmaceuticals relevant for the water cycle. Water Sci Technol 59:39–46CrossRefGoogle Scholar
  32. Ducrest AL, Keller L, Roulin A (2008) Pleiotropy in the melanocortin system, coloration and behavioural syndromes. Trends Ecol Evol 23:502–510CrossRefGoogle Scholar
  33. Exton JH (1985) Mechanisms involved in alpha-adrenergic phenomena. Am J Physiol Endocrinol Metab 248(6):E633–E647CrossRefGoogle Scholar
  34. Fabbri E (2015) Pharmaceuticals in the environment: expected and unexpected effects on aquatic fauna. Ann N Y Acad Sci 1340:20–28CrossRefGoogle Scholar
  35. Fabbri E, Franzellitti S (2016) Human pharmaceuticals in the marine environment: focus on exposure and biological effects in animal species. Environ Toxicol Chem 35:799–812CrossRefGoogle Scholar
  36. Fabbri E, Moon TW (2016) Adrenergic signaling in teleost fish liver, a challenging path. Comp Biochem Physiol B: Biochem Mol Biol 199:74–86CrossRefGoogle Scholar
  37. Fabbri E, Brighenti L, Ottolenghi C, Puviani AC, Capuzzo A (1992) β-Adrenergic receptors in catfish liver membranes: characterization and coupling to adenylate cyclase. Gen Comp Endocrinol 85(2):254–260CrossRefGoogle Scholar
  38. Fabbri E, Capuzzo A, Gambarotta A, Moon TW (1995) Characterization of adrenergic receptors and related transduction pathways in the liver of the rainbow trout. Comp Biochem Physiol B: Biochem Mol Biol 112(4):643–651CrossRefGoogle Scholar
  39. Fent K, Weston AA, Caminada D (2006) Ecotoxicology of human pharmaceuticals. Aquat Toxicol 76:122–159CrossRefGoogle Scholar
  40. Franzellitti S, Buratti S, Valbonesi P, Capuzzo A, Fabbria E (2011) The β-blocker propranolol affects cAMP-dependent signaling and induces the stress response in Mediterranean mussels, Mytilus galloprovincialis. Aquat Toxicol 101(2):299–308CrossRefGoogle Scholar
  41. French VA, Codi King S, Kumar A, Northcott G, Mcguinness K, Parry D (2015) Characterisation of microcontaminants in Darwin Harbour, a tropical estuary of northern Australia undergoing rapid development. Sci Total Environ 536:639–647CrossRefGoogle Scholar
  42. Fujii R (1961) Demonstration of the adrenergic nature of transmission at the junction between melanophore-concentrating nerve and melanophore in bony fish. J Facul Sci Univ Tokyo Sect IV9 171–196Google Scholar
  43. Fujii R, Novales RR (1972) Nervous control of melanosome movements in vertebrate melanophores. In: Riley V (ed) Pigmentation: its genesis and biologic control. Appleton-Century-Crofts, New York, pp 315–326Google Scholar
  44. Fukushima A, Sekiguchi W, Mamada K, Tohma Y, Ono H (2017) Serotonergic system does not contribute to the hypothermic action of acetaminophen. Biol Pharm Bull 40(2):227–233CrossRefGoogle Scholar
  45. Gether U (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21(1):90–113CrossRefGoogle Scholar
  46. Godoy AA, Kummrow F, Pamplin PA (2015) Occurrence, ecotoxicological effects and risk assessment of antihypertensive pharmaceutical residues in the aquatic environment—a review. Chemosphere 138:281–291CrossRefGoogle Scholar
  47. Grujić S, Vasiljević T, Lausević M (2009) Determination of multiple pharmaceutical classes in surface and ground waters by liquid chromatography-ion trap-tandem mass spectrometry. J Chromatogr A 1216(25):4989–5000CrossRefGoogle Scholar
  48. Halling-Sorensen B, Nors-Nielsen S, Lanzky PF, Ingerslev F, Holten-Lützhoft HC, Jorgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment—a review. Chemosphere 36(2):357–393CrossRefGoogle Scholar
  49. Healey EG, Ross OM (1966) The effects of drugs on the background response of the minnow Phoxinus phoxinus L. Comp Biochem Physiol 19:545–580CrossRefGoogle Scholar
  50. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol Lett 131:5–17CrossRefGoogle Scholar
  51. Hirsimäki P (1983) Vinblastine-induced autophagocytosis: effects on liver glycogen. FEBS Lett 151(1):89–93CrossRefGoogle Scholar
  52. Hoelz LV, De Freitas GB, Torres PHM, Fernandes TVA, Albuquerque MG, Da Silva JFM, De Alencastro RB (2013) Receptores Acoplados à Proteína G. Revista Virtual de Química 5(5):981–1000CrossRefGoogle Scholar
  53. Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D (2002) Toxicity of select beta adrenergic receptor-blocking pharmaceuticals (β-blockers) on aquatic organisms. Arch Environ Contam Toxicol 43:229–235CrossRefGoogle Scholar
  54. Janssens PA, Grigg JA (1988) Binding of adrenergic ligands to liver plasma membrane preparations from the axolotl, Ambystoma mexicanum; the toad, Xenopus laevis; and the Australian lungfish, Neoceratodus forsteri. Gen Comp Endocrinol 71(3):524–530CrossRefGoogle Scholar
  55. Janssens PA, Lowrey P (1987) Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio. Am J Phys Regul Integr Comp Phys 252(4):R653–R660Google Scholar
  56. Jozwiak-Bebenista M, Nowak JZ (2014) Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm Drug Res 71(1):11–23Google Scholar
  57. Junqueira LCU, Junqueira LMMS (1983) Técnicas básicas de citologia e histologia. Santos, São PauloGoogle Scholar
  58. 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 Anim 47(10):698–706CrossRefGoogle Scholar
  59. Kawashima T, Zwart MF, Yang CT, Mensh BD, Ahrens MB (2016) The serotonergic system tracks the outcomes of actions to mediate short-term motor learning. Cell 167(4):933–946CrossRefGoogle Scholar
  60. Kim JW, Jang HS, Kim JG, Ishibashi H, Hirano M, Nasu K, Ichikawa N, Takao Y, Shinohara R, Arizono K (2009) Occurrence of pharmaceutical and personal care products (PPCPs) in surface water from Mankyung River, South Korea. J Health Sci 55(2):249–258CrossRefGoogle Scholar
  61. Kotoulas OB, Kalamidas SA, Kondomerkos DJ (2006) Glycogen autophagy in glucose homeostasis. Pathol Res Pract 202(9):631–638CrossRefGoogle Scholar
  62. Lemes AS, Braccini MC (2004) Descrição e análise histológica das glândulas anexas do trato digestório de Hoplias malabaricus (Bloch, 1794), (Teleostei, Erythrinidae). Biodiversidade Pampeana 2(1):33–41Google Scholar
  63. Li G, Chen JB, Wang C, Xu Z, Nie H, Qin XY, Gong Q (2013) Curcumin protects against acetaminophen-induced apoptosis in hepatic injury. World J Gastroenterol: WJG 19(42):7440–7446CrossRefGoogle Scholar
  64. Lin AY, Tsai Y (2009) Occurrence of pharmaceuticals in Taiwan’s surface waters: impact of waste streams from hospitals and pharmaceutical production facilities. Sci Total Environ 407(12):3793–3802CrossRefGoogle Scholar
  65. Loffler D, Römbke J, Meller M, Ternes TA (2005) Environmental fate of pharmaceuticals in water/sediment systems. Environ Sci Technol 39:5209–5218CrossRefGoogle Scholar
  66. Lucinda PHF (2008) Systematics and biogeography of the poecilid fishes genus Phalloceros with the descriptions of twenty-one new species. Neotrop Ichthyol 6(2):113–158CrossRefGoogle Scholar
  67. Magno LDP, Fontes A, Gonçalves BMN, Gouveia A (2015) Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): waterborne administration. Pharmacol Biochem Behav 135:169–176CrossRefGoogle Scholar
  68. Marcon L, Bazzoli N, Honor MA, Anjos-benjamin LD (2015) Histological and Histometric evaluation of the liver in Astyanax Bimaculatus (Teleostei: Characidae), exposed to different concentrations of an organochlorine insecticide. Anat Rec 298(10):1754–1764CrossRefGoogle Scholar
  69. Maximino C, Marques de Brito T, CAG D, Gouveia A Jr, Morato S (2010) Scototaxis as anxiety-like behavior in fish. Nat Protoc 5(2):209–216CrossRefGoogle Scholar
  70. Mcdonald DG, Tang Y, Boutiller W (1989) The role of β-adrenoreceptors in the recovery from exhaustive exercise of freshwater-adapted trout. J Exp Biol 147:471–449Google Scholar
  71. Mcmanus JFA (1946) Histological demonstration of mucin after periodic acid. Nature 158:202CrossRefGoogle Scholar
  72. Menezes NA, Weitzman SH, Oyakawa OT, De Lima FCT, Castro RMC, Weitzman MJ (2007) Peixes de água doce da Mata Atlântica: lista preliminar das espécies e comentários sobre conservação de peixes de água doce neotropicais. Museu de Zoologia da Universidade de São PauloGoogle Scholar
  73. Menezes-Faria JCND (2009) Histopathological, histochemical and morphometric evaluation of the effects of the acute toxicity of the roundup® herbicide on the gills and liver of the fish Poecilia vivipara (Text in portuguese)Google Scholar
  74. Merrick BA, Bruno ME, Madenspacher JH, Wetmore BA, Foley J, Pieper R, Taylor J (2006) Alterations in the rat serum proteome during liver injury from acetaminophen exposure. J Pharmacol Exp Ther 318(2):792–802CrossRefGoogle Scholar
  75. Miao XS, Koenig BG, Metcalfe CD (2002) Analysis of acidic drugs in the effluents of sewage treatment plants using liquid chromatography–electrospray ionization tandem mass spectrometry. J Chromatogr 952:139–147CrossRefGoogle Scholar
  76. Mitchell KM, Moon TW (2016) Behavioral and biochemical adjustments of the zebrafish Danio rerio exposed to the β-blocker propranolol. Comp Biochem Physiol B Biochem Mol Biol 199:105–114CrossRefGoogle Scholar
  77. Miyashita Y, Fujii R (1975) Receptor mechanisms in fish chromatophores—II. Evidence for beta adrenoceptors mediating melanosome dispersion in Guppy melanophores. Comp Biochem Physiol C Comp Pharmacol 51(2):179–187CrossRefGoogle Scholar
  78. Moiseenko TI (2008) Aquatic ecotoxicology: theoretical principles and practical application. Water Resour 35(5):530–541CrossRefGoogle Scholar
  79. North TE, Babu IR, Vedder LM, Lord AM, Wishnok JS, Tannenbaum SR, Goessling W (2010) PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc Natl Acad Sci 107(40):17315–17320CrossRefGoogle Scholar
  80. Nunes B (2011) The use of cholinesterases in ecotoxicology. Rev Environ Contam Toxicol 212:29–59Google Scholar
  81. Nunes B, Carvalho F, Guilhermino L (2005) Acute toxicity of widely used pharmaceuticals in aquatic species: Gambusia holbrooki, Artemia parthenogenetica and Tetraselmis chuii. Ecotoxicol Environ Saf 61:413–419CrossRefGoogle Scholar
  82. 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 71:341–354CrossRefGoogle Scholar
  83. 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 107:178–185CrossRefGoogle Scholar
  84. Nunes B, Verde MF, Soares AM (2015) Biochemical effects of the pharmaceutical drug paracetamol on Anguilla anguilla. Environ Sci Pollut Res 22(15):11574–11584CrossRefGoogle Scholar
  85. OECD Organization for the Economic Cooperation and Development (2009) Draft Guidance Document The Threshold Approach for Acute Fish Toxicity Testing. Organization for Economic Cooperation and Development, Paris, France.Google Scholar
  86. OECD Organization for the Economic Cooperation and Development (1992a) OECD Guidelines for testing chemicals 203: fish, acute toxicity test 1–9Google Scholar
  87. OECD Organization for the Economic Cooperation and Development (1992b) OECD Guidelines for testing chemicals 203: fish, acute toxicity test 1–18Google Scholar
  88. OECD Organization for the Economic Cooperation and Development (1998) OECD Guidelines for testing chemicals 215: Fish, Short-term Toxicity Test on Embryo and Sac-fry Stages 1–20Google Scholar
  89. OECD Organization for the Economic Cooperation and Development (2000) OECD Guidelines for testing chemicals 215: fish, Juvenile Growth Test 1–16Google Scholar
  90. Owen SF, Giltrow E, Huggett DB, Hutchinson TH, Saye J, Winter MJ, Sumpter JP (2007) Comparative physiology, pharmacology and toxicology of β-blockers: mammals versus fish. Aquat Toxicol 82(3):145–162CrossRefGoogle Scholar
  91. Padilla S (1995) Regulatory and research issues related to cholinesterase inhibition. Toxicology 102(1):215–220CrossRefGoogle Scholar
  92. Papackova Z, Heczkova M, Dankova H, Sticova E, Lodererova A, Bartonova L, Cahova M (2018) Silymarin prevents acetaminophen-induced hepatotoxicity in mice. PLoS One 13(1):e0191353CrossRefGoogle Scholar
  93. Pearse AGE (1960) Histochemistry theoretical and applied. J. & A. Churchill, LondonGoogle Scholar
  94. Pereira VM, Bortolotto JW, Kist LW, De Azevedo MB, Fritsch RS, Da Luz Oliveira R, Bogo MR (2012) Endosulfan exposure inhibits brain AChE activity and impairs swimming performance in adult zebrafish (Danio rerio). Neurotoxicology 33(3):469–475CrossRefGoogle Scholar
  95. Pereira BV, Matus GN, Costa MJ, Dos Santos ACA, Silva-Zacarin EC, do Carmo JB, 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):14899–14910CrossRefGoogle Scholar
  96. Petcoff GM, Díaz AO, Escalante AH, Goldemberg AL (2006) Histology of the liver of Oligosarcus jenynsii (Ostariophysi, Characidae) from Los Padres Lake, Argentina. Iheringia Série Zoologia 96(2):205–208CrossRefGoogle Scholar
  97. Petrović M, Gonzalez S, Barceló D (2003) Analysis and removal of emerging contaminants in wastewater and drinking water. Trends Anal Chem 22:685–696CrossRefGoogle Scholar
  98. Pini LA, Sandrini M, Vitale G (1996) The antinociceptive action of paracetamol is associated with changes in the serotonergic system in the rat brain. Eur J Pharm Sci 308(1):31–40CrossRefGoogle Scholar
  99. Ramos AS, Correia AT, Antunes SC, Gonçalves F, Nunes B (2014) Effect of acetaminophen exposure in Oncorhynchus mykiss gills and liver: detoxification mechanisms, oxidative defence system and peroxidative damage. Environ Toxicol Pharmacol 37:1221–1228CrossRefGoogle Scholar
  100. Roberts PH, Thomas KV (2006) The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment. Sci Total Environ 356:143–153CrossRefGoogle Scholar
  101. Rodrigues S, Antunes SC, Brandão FP, Castro BB, Goncalves F, Nunes B (2012) Effects of anticholinesterase drugs on biomarkers and behavior of pumpkin-seed, Lepomis gibbosus (Linnaeus, 1758). J Environ Monit 14:1638–1644CrossRefGoogle Scholar
  102. Rodrigues S, Correia AT, Antunes SC, Nunes B (2014) Alterations in gills of Lepomis gibbosus, after acute exposure to several xenobiotics (pesticide, detergent and pharmaceuticals): morphometric and biochemical evaluation. Drug Chem Toxicol 38:1–7Google Scholar
  103. Scheline RR (1963) Adrenergic mechanisms in fish: chromatophore pigment concentration in cuckoo wrasse, Labrus ossifagus L. Comp Biochem Physiol 9:215–227CrossRefGoogle Scholar
  104. Schrap SM, RijS GB, Beek MA, Maaskant JF, Staeb J, Stroomberg G, Tiesnitsch J (2003) Humane en veterinaire geneesmiddelen in Nederlands oppervlaktewater en afvalwater. Ministerie van Verkeer en Waterstaat, Directoraat-Generaal Rijkswaterstaat, RIZA Rijksinstituut voor Integraal Zoetwaterbeheer en Afvalwaterbehandeling: RIZA report, p 86Google Scholar
  105. Scott GT (1965) Physiology and pharmacology of color change in the sand flounder Scopthalamus aquosus. Limnol Oceanogr 10:230–246CrossRefGoogle Scholar
  106. Shivashri C, Rajarajeshwari T, Rajasekar P (2013) Hepatoprotective action of celery (Apium graveolens) leaves in acetaminophen-fed freshwater fish (Pangasius sutchi). Fish Physiol Biochem 39(5):1057–1069CrossRefGoogle Scholar
  107. Silva-Zacarin ECM, Chauzat MP, Zeggane S, Drajnudel P, Schurr F, Faucon JP, Engler JA (2012) Protocol for optimization of histological, histochemical and immunohistochemical analyses of larval tissues: application in histopathology of honey bee, Current microscopy contributions to advances in science and technology. Formatex Research Center, Badajoz, pp 696–703Google Scholar
  108. Sköld HN, Aspengren S, Cheney KL, Wallin M (2016) Chapter four—fish chromatophores—from molecular motors to animal behavior. Int Rev Cell Mol Biol 321:171–219CrossRefGoogle Scholar
  109. Sodré FF, Montagner CC, Locatelli MAF, Jardim WF (2007) Ocorrência de Interferentes Endócrinos e Produtos Farmacêuticos em Águas Superficiais da Região de Campinas (SP, Brasil). J Braz Soc Ecotoxicol 2:187–196CrossRefGoogle Scholar
  110. Sodré FF, Locatelli FMA, Jardim FW (2010) Occurrence of emerging contaminants in Brazilian drinking waters: a sewage-to-tap issue. Water Air Soil Pollut 206:57–67CrossRefGoogle Scholar
  111. 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):649–656CrossRefGoogle Scholar
  112. Stanley JK, Ramirez AJ, Mottaleb M, Chambliss CK, Brooks BW (2006) Enantiospecific toxicity of the β-blocker propranolol to Daphnia magna and Pimephales promelas. Environ Toxicol Chem 25(7):1780–1786CrossRefGoogle Scholar
  113. Sugimoto M (2002) Morphological color changes in fish: regulation of pigment cell density and morphology. Microsc Res Tech 58(6):496–503CrossRefGoogle Scholar
  114. Summers CH, Winberg S (2006) Interactions between the neural regulation of stress and aggression. J Exp Biol 209(23):4581–4589CrossRefGoogle Scholar
  115. Ternes AT (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260CrossRefGoogle Scholar
  116. van der Oost R, Beyer J, NPE V (2003) Fish bioaccumulation and biomarkers in environmental risk assessment: a review. Environ Toxicol Pharmacol 13:57–149CrossRefGoogle Scholar
  117. Van der Salm AL, Pavlidis M, Flik G, Wendelaar Bonga SE (2006) The acute stress response of red porgy, Pagrus pagrus, kept on a red or white background. Gen Comp Endocrinol 145(3):247–253CrossRefGoogle Scholar
  118. Van Donk E, Peacor S, Grosser K, LNDS D, Lürling M (2016) Pharmaceuticals may disrupt natural chemical information flows and species interactions in aquatic systems: ideas and perspectives on a hidden global change. Rev Environ Contam Toxicol 238:91–105Google Scholar
  119. Van Heeswijk JC, Vianen GJ, Van den Thillart GE (2006) The adrenergic control of hepatic glucose and FFA metabolism in rainbow trout (Oncorhynchus mykiss): increased sensitivity to adrenergic stimulation with fasting. Gen Comp Endocrinol 145(1):51–61CrossRefGoogle Scholar
  120. Vicentini CA, Franceschini-Vicentini IB, Bombonato MTS, Bertolucci B, Lima SG, Santos AS (2005) Morphological study of the liver in the teleost Oreochromis niloticus. Int J Morphol 23(3):211–216CrossRefGoogle Scholar
  121. Vidal BC (1970) Dichroism on collagen bundles stained with Xylidine ponceau 2R. Ann Histochim 15:289–296Google Scholar
  122. Wallace JL (2004) Acetaminophen hepatotoxicity: NO to the rescue. Br J Pharmacol 143(1):1–2CrossRefGoogle Scholar
  123. Welsch UN, Storch VN (1973) Enzyme histochemical and ultrastructural observations on the liver of teleost fishes. Arch Histol Jap 36(1):21–37CrossRefGoogle Scholar
  124. Wilson JM, Bunte RM, Carty AJ (2009) Evaluation of rapid cooling and tricaine methanesulfonate (MS222) as methods of euthanasia in zebrafish (Danio rerio). J Am Assoc Lab Anim Sci 48(6):785–789Google Scholar
  125. Winberg S, Nilsson GE (1993) Roles of brain monoamine neurotransmitters in agonistic behaviour and stress reactions, with particular reference to fish. Comp Biochem Physiol C Comp Pharmacol Toxicol 106(3):597–614Google Scholar
  126. Wolff LL, Donatti L (2016) Estudo do comportamento do peixe de água doce Phalloceros harpagos (Cyprinodontiformes: Poeciliidae) submetido à alteração artificial do pH. Lumin. União da Vitó-ria 18(1):10–21Google Scholar
  127. Wolf JC, Wolfe MJ (2005) A brief overview of nonneoplastic hepatic toxicity in fish. Toxicol Pathol 33(1):75–85CrossRefGoogle Scholar
  128. Xia L, Zheng L, Zhou JL (2017) Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in developing zebrafish (Danio rerio). Chemosphere 182:416–425CrossRefGoogle Scholar
  129. Xu JJ, Hendriks BS, Zhao J, de Graaf D (2008) Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology. FEBS Lett 582(8):1276–1282CrossRefGoogle Scholar
  130. Yamamoto H, Nakamura Y, Nakamura Y, Kitani C, Imari T, Sekizawa J, Takao Y, Yamashita N, Hirai N, Oda S, Tatarazako N (2007) Initial ecological risk assessment of eight selected human pharmaceuticals in Japan. Environ Sci 14:177–193Google Scholar
  131. Yin L, Ma R, Wang B, Yuan H, Yu G (2017) The degradation and persistence of five pharmaceuticals in an artificial climate incubator during a one year period. RSC Adv 7:8280–8287CrossRefGoogle Scholar
  132. You L, Nguyen VT, Pal A, Chen H, He Y, Reinhard M, Gin KY (2015) Investigation of pharmaceuticals, personal care products and endocrine disrupting chemicals in a tropical urban catchment and the influence of environmental factors. Sci Total Environ 536:955–963CrossRefGoogle Scholar
  133. Zhou JL, Zhang ZL, Banks E, Grover D, Jiang JQ (2009) Pharmaceutical residues in wastewater treatment works effluents and their impact on receiving river water. J Hazard Mater 166(2–3):655–661CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Gregorio Nolazco Matus
    • 1
  • Beatriz V. R. Pereira
    • 1
  • Elaine C. M. Silva-Zacarin
    • 1
    • 2
  • Monica Jones Costa
    • 1
    • 2
  • André Cordeiro Alves dos Santos
    • 2
  • Bruno Nunes
    • 3
    • 4
    Email author
  1. 1.Pós-Graduação em Biotecnologia e Monitoramento Ambiental (PPGBMA)Universidade Federal de São Carlos (UFSCar)SorocabaBrazil
  2. 2.Departamento de BiologiaUniversidade Federal de São CarlosSorocabaBrazil
  3. 3.Departamento de BiologiaUniversidade de AveiroAveiroPortugal
  4. 4.Centro de Estudos do Ambiente e do Mar (CESAM, Laboratório Associado)Universidade de AveiroAveiroPortugal

Personalised recommendations