Skip to main content
SpringerLink
Log in

Biochemical effects of acetaminophen in aquatic species: edible clams Venerupis decussata and Venerupis philippinarum

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

Abstract

Acetaminophen (paracetamol) is one of the most used pharmaceutical drugs, due to its antipyretic and analgesic properties that turn it into a primary choice in varied pathologies and conditions. However, and despite its massive use, acetaminophen is not exempt of adverse effects, especially when administered in over dosage, which are related to the formation of toxic metabolites by oxidative pathways. It is thus possible to observe that toxicity caused by acetaminophen is usually mediated by reactive oxygen species and can result in multiple effects, ranging from protein denaturation to lipid peroxidation and DNA damage. The occurrence of acetaminophen has been reported in the aquatic environment, being important to address the potential exertion of toxic effects on nontarget environmentally exposed organisms. The present study intended to characterize the effects of acute acetaminophen exposure on physiological traits (antioxidant defense, oxidative damage) of two species of bivalves, namely, the edible clams Venerupis decussata and Venerupis philippinarum. Results showed a significant increase in all oxidative stress biomarkers, evidencing the bioactivation of acetaminophen into a deleterious prooxidant, triggering the onset of deleterious effects. Furthermore, strong interspecific differences were observed among responses of the two tested species, which was a major issue due to intrinsic ecological implications when one considers that both species share the same habitat.

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

Similar content being viewed by others

References

  • Adamson GM, Harman AW (1989) A role for the glutathione peroxidase/reductase enzyme system in the protection from paracetamol toxicity in isolated mouse hepatocytes. Biochem Pharmacol 38(19):3323–3330

    Article  CAS  Google Scholar 

  • Ahmida MH (2010) Evaluation of in vivo antioxidant and hepatoprotective activity of Portulaca oleracea L. against paracetamol-induced liver toxicity in male rats. Am J Pharmacol Toxicol 5(4):167–176

    CAS  Google Scholar 

  • Bergman K, Müller L, Weberg Teigen S (1996) The genotoxicity and carcinogenicity of paracetamol: a regulatory (re)view. Mutat Res Fundam Mol Mech Mutagen 349(2):263–288

    Article  Google Scholar 

  • Boxall ABA (2004) The environmental side effects of medication. EMBO Rep 5(12):1110–1116

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Brandão FP, Pereira JL, Gonçalves F, Nunes B (2011) The impact of paracetamol on selected biomarkers of the mollusc species Corbicula fluminea. Environ Toxicol. doi:10.1002/tox.20774

    Google Scholar 

  • Brillas E, Sirés I, Aria C, Cabot PL, Centellas F, Rodríguez RM, Garrido JA (2005) Mineralization of paracetamol in aqueous medium by anodic oxidation with a boron-doped diamond electrode. Chemosphere 58:399–406

    Article  CAS  Google Scholar 

  • Brind AM (2007) Drugs that damage the liver. Medicine 35(1):26–30

    Article  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  CAS  Google Scholar 

  • Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    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 

  • Conners DE (2004) Biomarkers of oxidative stress in freshwater clams (Corbicula fluminea) as mechanistic tools to evaluate the impairment of stream ecosystem health by lawn care pesticides. University of Georgia.http://getd.galib.uga.edu/public/conners_deanna_e_200405_phd/conners_deanna_e_200405_phd.pdf. Accessed 18 Mar 2011

  • Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 107:907–938

    Article  CAS  Google Scholar 

  • Delgado M, Pérez-Camacho A (2007) Comparative study of gonadal development of Ruditapes philippinarum (Adams and Reeve) and Ruditapes decussatus (L.) (Mollusca: Bivalvia): influence of temperature. Sci Mar 71:471–484

    Article  Google Scholar 

  • Donaghy L, Lambert C, Choi KS, Soudant P (2009) Hemocytes of the carpet shell clam (Ruditapes decussatus) and the Manila clam (Ruditapes philippinarum): current knowledge and future prospects. Aquaculture 297:10–24

    Article  Google Scholar 

  • EPA (1996a) Ecological effects test guidelines, OPPTS 850.1025 oyster acute toxicity test (shell deposition). EPA, Washington DC, US

    Google Scholar 

  • EPA (1996b) Ecological effects test guidelines, OPPTS 850.1710 oyster BCF. US EPA, Washington, D.C

    Google Scholar 

  • FAO (1996) Fishery statistics capture production. Food and Agriculture Organization of the United Nations. Rome 82:399–400

    Google Scholar 

  • FAO (2005) Cultured aquatic species information programme. R. philippinarum. In: Goulletquer P (ed) Cultured aquatic species information programme. FAO Fisheries and Aquaculture Department, Rome

    Google Scholar 

  • FAO (2009) FishStat Plus—universal software for fishery statistical time series. FAO Fisheries and Aquaculture Department, Rome

    Google Scholar 

  • FAO (2011) Review of the state of world marine fishery resources. FAO Fisheries and Aquaculture Technical Paper No. 569 Rome

  • Figueira E, Cardoso P, Freitas R (2012) Ruditapes decussatus and Ruditapes philippinarum exposed to cadmium: toxicological effects and bioaccumulation patterns. Comp Biochem Physiol C 156:80–86

    CAS  Google Scholar 

  • Flassch JP, Leborgne Y (1992) Introduction in Europe, from 1972 to 1980, of the Japanese Manila clam (Tapes philippinarum) and the effects on aquaculture production and natural settlement. ICES Mar Sci Symp 194:92–96

    Google Scholar 

  • Freitas R, Ramos Pinto L, Sampaio M, Costa A, Silva M, Rodrigues AM, Quintino V, Figueira E (2012) Effects of depuration on the element content in bivalves: comparison between sympatric Ruditapes decussatus and Ruditapes philippinarum. Estuarine Coastal Shelf Sci 110:43–53

    Article  CAS  Google Scholar 

  • Ganiyat AM (2008) The toxicological evaluation of sewage effluents and pharmaceuticals with the use of zebrafish as a model organism. Master of Science Programme in Veterinary Medicine for International Students. Faculty of Veterinary Medicine and Animal Science. Swedish University of Agricultural Sciences 7:1403–2201

  • Gosling E (2002) Bivalve molluscs: biology, ecology and culture. Fishing News Books, Oxford

    Google Scholar 

  • Gros M, Rodríguez-Mozaz S, Barceló D (2012) Fast and comprehensive multi-residue analysis of a broad range of human and veterinary pharmaceuticals and some of their metabolites in surface and treated waters by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry. J Chromatogr A 1248:104–121

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-S-transferases—the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  Google Scholar 

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

    Article  Google Scholar 

  • Hamid ZA, Budin SB, Jie NW, Hamid A, Husain K, Mohamed J (2012) Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract against paracetamol-induced nephrotoxicity and oxidative stress in rats. J Zhejiang Univ Sci B 13(3):176–185

    Article  Google Scholar 

  • Hamza-Chaffai A, Amiard JC, Cosson RP (1999) Relationship between metallothioneins and metals in a natural population of the clam Ruditapes decussatus from Sfax coast: a non-linear model using Box-Cox transformation. Comp Biochem Physiol C 123:153–163

    CAS  Google Scholar 

  • Hinson JA, Reid AB, McCullough SS, James LP (2004) Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab 36(3–4):805–822, Abstract

    CAS  Google Scholar 

  • INE (2007) Estatística da pesca 2006. Instituto Nacional de Estatística, Lisboa, 97 pp

    Google Scholar 

  • Jaeschke H, Bajt ML (2006) Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 89(1):31–41

    Article  CAS  Google Scholar 

  • Jaeschke H, Knight TR, Bajt ML (2003) The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity. Toxicol Lett 144:279–288

    Article  CAS  Google Scholar 

  • Jensen AC, Humphreys J, Caldow RWG, Grisley C, Dyrynda PEJ (2004) Naturalization of the Manila clam (Ruditapes philippinarum), an alien species, and establishment of a clam fishery within Poole Harbour, Dorset. J Mar Biol Assoc U K 84:1069–1073

    Article  Google Scholar 

  • Jones OAH, Voulvoulis N, Lester JN (2002) Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Res 36:5013–5022

    Article  CAS  Google Scholar 

  • 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):698–706

    Article  CAS  Google Scholar 

  • Kim WS, Huh HT, Huh S-H, Lee TW (2001) Effects of salinity on endogenous rhythm of the manila clam, Ruditapes philippinarum (Bivalvia: Veneridae). Mar Biol 138:157–162

    Article  CAS  Google Scholar 

  • Kim Y, Choi K, Jung J, Park S, Kim P-G, Park J (2007) Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six major sulfonamides, and their potential ecological risks in Korea. Environ Int 33:370–375

    Article  CAS  Google Scholar 

  • Klaassen CD (2001) Casarett & Doull’s toxicology: the basic science of poisons, 6th edn. McGraw-Hill, New York

    Google Scholar 

  • Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36(6):1202–1211

    Article  CAS  Google Scholar 

  • Kozer E, Evans S, Barr J, Greenberg R, Soriano I, Bulkowstein M, Petrov I, Chen-Levi Z, Barzilay B, Berkovitch M (2003) Glutathione, glutathione-dependent enzymes and antioxidant status in erythrocytes from children treated with high-dose paracetamol. Br J Clin Pharmacol 55(3):234–240

    Article  CAS  Google Scholar 

  • Livingstone DR (2001) Contaminant-stimulated reactive oxygen species production and oxidative damage in aquatic organisms. Mar Pollut Bull 42(8):656–666

    Article  CAS  Google Scholar 

  • Lourenção BC, Medeiros RA, Filho RCR, Mazo LH, Filho OF (2009) Simultaneous voltammetric determinate on of paracetamol and caffeine in pharmaceutical formulations using a boron-doped diamond electrode. Talanta 78:748–752

    Article  Google Scholar 

  • Miao XS, Koenig BG, Metcalfe CD (2002) Analysis of acidic drugs in the effluents of sewage treatment plants using liquid chromatography-electrospray ionisation tandem mass spectrometry. J Chromatogr A 952:139–147

    Article  CAS  Google Scholar 

  • Murray KE, Thomas SM, Bodour AA (2010) Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment. Environ Pollut 158:3462–3471

    Article  CAS  Google Scholar 

  • Niki E (2012) Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products? FEBS Lett 586(21):3767–3770

    Article  CAS  Google Scholar 

  • 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 62:581–594

    Article  CAS  Google Scholar 

  • 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 71:341–354

    Article  CAS  Google Scholar 

  • Olaleye MT, Rocha J (2008) Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. Exp Toxicol Pathol 59(5):319–327

    Article  CAS  Google Scholar 

  • Orhan H, Sahin G (2001) In vitro effects of NSAIDS and paracetamol on oxidative stress-related parameters of human erythrocytes. Exp Toxicol Pathol 53(2–3):133–140

    Article  CAS  Google Scholar 

  • Parolini M, Binelli A, Cogni D, Provini A (2010) Multi-biomarker approach for the evaluation of the cyto-genotoxicity of paracetamol on the zebra mussel (Dreissena polymorpha). Chemosphere 79(5):489–498

    Article  CAS  Google Scholar 

  • Patel M, Tang BK, Kalow W (1992) Variability of acetaminophen metabolism in Caucasians and Orientals. Pharmacogenetics 2(1):38–45

    Article  CAS  Google Scholar 

  • Petrovic M, Lopez de Alda MJ, Diaz-Cruz S, Postigo C, Radjenovic J, Gros M, Barcelò D (2009) Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration. Phil Trans R Soc A 367:3979–4003

    Article  CAS  Google Scholar 

  • Pravoni F, Franceschini G, Casale M, Zucchetta M, Torricelli P, Giovanardi O (2006) An ecological imbalance induced by a non-native species: the Manila clam in the Venice Lagoon. Biol Inv 8:595–609

    Article  Google Scholar 

  • Prescott LF (1980) Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 10:291S–298S

    Article  Google Scholar 

  • Ramos AS, Gonçalves F, Antunes SC, Nunes B (2012) Cholinesterase characterization in Corbicula fluminea and effects of relevant environmental contaminants: a pesticide (chlorfenvinphos) and a detergent (SDS). J Environ Sci Health B47(6):512–519

    Article  CAS  Google Scholar 

  • 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(1–3):143–153

    Article  CAS  Google Scholar 

  • Sebastine IM, Wakeman RJ (2003) Consumption and environmental hazards of pharmaceutical substances in the UK. Process Saf Environ Prot 81(B4):229–235

    Article  CAS  Google Scholar 

  • Silva DGH, Junior EB, Torres LS, Júnior OR, Lobo CC, Bonini-Domingos CR, Almeida EA (2011) Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia. Blood Cells Mol Dis 47(1):23–28

    Article  CAS  Google Scholar 

  • Singh S, Singh S, Kumar M, Chandra K, Singh R (2011) Ameliorative potential of quercetin against paracetamol-induced oxidative stress in mice blood. Toxicol Int 18(2):140–145

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Solidoro C, Pastres R, Melaku Canu D, Pellizzato M, Rossi R (2000) Modelling the growth of Tapes philippinarum in the lagoon of Venice. Mar Ecol Prog Ser 199:137–148

    Article  Google Scholar 

  • Tanguy A, Bierne N, Saavedra C, Pina B, Bachère E, Kube M, Bazin E, Bonhomme F, Boudry P, Boulo V, Boutet I, Cancela L, Dossat C, Favrel P, Huvet A, Jarque S, Jollivet D, Klages S, Lapègue S, Leite R, Moal J, Moraga D, Reinhardt R, Samain JF, Zouros E, Canario A (2008) Increasing genomic information in bivalves through new EST collections in four species, development of new genetic markers for environmental studies and genome evolution. Gene 408:27–36

    Article  CAS  Google Scholar 

  • Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32(11):3245–3260

    Article  CAS  Google Scholar 

  • Thomas KV, Dye C, Schlabach M, Langford KH (2007) Source to sink tracking of selected human pharmaceuticals from two Oslo city hospitals and a wastewater treatment works. J Environ Monit 9:1410–1418

    Article  CAS  Google Scholar 

  • Usero J, González-Regalado E, Garcia I (1997) Trace metals in the bivalve molluscs Ruditapes decussatus and Ruditapes philippinarum from the Atlantic coast of Southern Spain. Environ Int 23:291–298

    Article  CAS  Google Scholar 

  • Vidal ML, Bassères A, Narbonne JF (2001) Potential biomarkers of trichloroethylene and toluene exposure in Corbicula fluminea. Environ Toxicol Pharmacol 9:87–97

    Article  CAS  Google Scholar 

  • Winker M, Faika D, Gulyas H, Otterpohl R (2008) A comparison of human pharmaceutical concentrations in raw municipal wastewater and yellowwater. Sci Total Environ 399:96–104

    Article  CAS  Google Scholar 

  • Xu JJ, Hendriks BS, Zhao J, Graaf D (2008) Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology. FEBS Lett 582:1276–1282

    Article  CAS  Google Scholar 

  • Yang L, Yu LE, Ray MB (2008) Degradation of paracetamol in aqueous solutions by TiO2 photocatalysis. Water Res 42:3480–3488

    Article  CAS  Google Scholar 

  • Yousef MI, Omar SAM, El-Guendia MI, Laila A, Abdelmegid LA (2010) Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 48(11):3246–3261

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Biologia da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre s/n, 4169-007, Porto, Portugal

    S. C. Antunes

  2. Departamento de Biologia, Universidade de Aveiro, 3810-193, Aveiro, Portugal

    Rosa Freitas, E. Figueira, Fernando Gonçalves & Bruno Nunes

  3. Centro de Estudos do Ambiente e do Mar (CESAM), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    S. C. Antunes, Rosa Freitas, E. Figueira, Fernando Gonçalves & Bruno Nunes

Authors
  1. S. C. Antunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosa Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Figueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernando Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bruno Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruno Nunes.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antunes, S.C., Freitas, R., Figueira, E. et al. Biochemical effects of acetaminophen in aquatic species: edible clams Venerupis decussata and Venerupis philippinarum . Environ Sci Pollut Res 20, 6658–6666 (2013). https://doi.org/10.1007/s11356-013-1784-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-013-1784-9

Keywords

Search

Navigation