Skip to main content
Log in

Acute Effects of Tetracycline Exposure in the Freshwater Fish Gambusia holbrooki: Antioxidant Effects, Neurotoxicity and Histological Alterations

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 6:105–121

    Google Scholar 

  • Alazemi BM, Lewis JW, Andrews EB (1996) Gill damage in the fresh water fish Gnathonemus petersii (family: Mormyridae) exposed to selected pollutants: an ultrastructural study. Environ Technol 17(3):225–238

    Article  CAS  Google Scholar 

  • Amacher DE, Martin BA (1997) Tetracycline-induced steatosis in primary canine hepatocyte cultures. Fundam App Toxicol 40(2):256–263

    Article  CAS  Google Scholar 

  • Asha KK, Sankar TV, Nair PGV (2007) Effect of tetracycline on pancreas and liver function of adult male albino rats. J Pharmacy Pharmacol 59:1241–1248

    Article  CAS  Google Scholar 

  • Barceló D (2003) Emerging pollutants in water analysis. Trends Anal Chem 22(10):15–16

    Article  Google Scholar 

  • 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(1):25–34

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Brunelli E, Mauceri A, Maisano M, Bernabo I, Giannetto A, De Domenico E et al (2011) Ultrastructural and immunohistochemical investigation on the gills of the teleost, Thalassoma pavo L., exposed to cadmium. Acta Histochem 113:201–213

    Article  CAS  Google Scholar 

  • Bruno DW (1989) An investigation into oxytetracycline residues in Atlantic salmon, Salmo salar L. J Fish Dis 12(2):77–86

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Cabello FC (2006) Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment. Environ Microbiol 8(7):1137–1144

    Article  CAS  Google Scholar 

  • Cabral A, Marques C (1999) Life history, population dynamics and production of eastern mosquito fish, Gambusia holbrooki (Pisces, Poeciliidae) in rice fields of the lower Mondego River Valley, Western Portugal. Acta Oecol 20(6):607–620

    Article  Google Scholar 

  • Camargo MMP, Martinez CBR (2007) Histopathology of gills, kidney and liver of a neotropical fish caged in an urban stream. Neotrop Ichthyol 5(3):327–336

    Article  Google Scholar 

  • Castiglioni S, Bagnati R, Calamari D, Fanelli R, Zuccato E (2005) A multiresidue analytical method using solid-phase extraction and high-pressure chromatography tandem mass spectrometry to measure pharmaceuticals of different therapeutic classes in urban waste waters. J Chromatogr A 1092(2):206–215

    Article  CAS  Google Scholar 

  • Cengiz E, Unlu E (2006) Sublethal effects of commercial deltamethrin on the structure of the gill, liver and gut tissues of mosquitofish, Gambusia affinis: a microscopic study. Environ Toxicol Pharmacol 21:246–253

    Article  CAS  Google Scholar 

  • Cerqueira MA, Vieira FN, Ferreira RV, Silva JF (2005) The water quality of the Cértima River Basin (Central Portugal). Environ Monit Assess 111:297–306

    Article  CAS  Google Scholar 

  • Chambers HF (2001) Cloramphenicol, tetracyclines, macrolides, clindamycin and streptogramins. In: Katzung BG (ed) Basic and clinical pharmacology, 8th edn. McGraw-Hill, New York, pp 774–783

    Google Scholar 

  • Chen WR, Huang CH (2009) Transformation of tetracyclines mediated by Mn(II) and Cu(II) ions in the presence of oxygen. Environ Sci Technol 43(2):401–407

    Article  CAS  Google Scholar 

  • Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142(3):185–194

    Article  CAS  Google Scholar 

  • Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle changes? Environ Health Perspect 107(6):907–938

    Article  CAS  Google Scholar 

  • De Domenico E, Mauceri A, Giordano G, Maisano M, Gioffrè G, Natalotto A et al (2011) Effects of “in vivo” exposure to toxic sediments on juveniles of sea bass (Dicentrarchus labrax). Aquat Toxicol 105:688–697

    Article  Google Scholar 

  • De Domenico E, Mauceri A, Giordano D, Maisano M, Giannetto A, Parrino V et al (2013) Biological responses of juvenile European sea bass (Dicentrarchus labrax) exposed to contaminated sediments. Ecotoxicol Environ Saf 97:114–123

    Article  Google Scholar 

  • Deblonde T, Cossu-Leguilla C, Hartemann P (2011) Emerging pollutants in wastewater: a review of the literature. Int J Hyg Environ Health 214:442–448

    Article  CAS  Google Scholar 

  • Díaz-Cruz MS, Alda MJL, Barceló D (2003) Environmental behavior and analysis of veterinary and human drugs in soils, sediments and sludge. Trends Anal Chem 22(6):340–351

    Article  Google Scholar 

  • Dong L, Gao J, Xie X, Zhou Q (2012) DNA damage and biochemical toxicity of antibiotics in soil on the earthworm Eisenia fetida. Chemosphere 89(1):44–51

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • Evans DH, Piermarini PM, Choe KP (2005) The multifunctional fish gill: dominant site of gas exchange, osmoregulation, acid-base regulation, and excretion of nitrogenous waste. Physiol Rev 85:97–177

    Article  CAS  Google Scholar 

  • Ezemonye LI, Ikpesu TO (2011) Evaluation of sub-lethal effects of endosulfan on cortisol secretion, glutathione S-transferase and acetylcholinesterase activities in Clarias gariepinus. Food Chem Toxicol 49(9):1898–1903

    Article  CAS  Google Scholar 

  • Fatta-Kassinos D, Meric S, Nikolaou A (2011) Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal Bioanal Chem 399:251–275

    Article  CAS  Google Scholar 

  • Fernandes MN, Mazon AF (2003) Environmental pollution and fish gill morphology. In: Val AL, Kapoor BG (eds) Fish adaptations. Science, Enfield, pp 203–231

    Google Scholar 

  • Fernandes C, Fontaínhas-Fernandes A, Rocha E, Salgado MA (2008) Monitoring pollution in Esmoriz-Paramos lagoon, Portugal: liver histological and biochemical effects in Liza saliens. Environ Monit Assess 145(1–3):315–322

    Article  CAS  Google Scholar 

  • Gravato C, Guimarães L, Santos J, Faria M, Alves A, Guilhermino L (2010) Comparative study about the effects of pollution on glass and yellow ells (Anguilla anguilla) from the estuaries of Minho, Lima and Douro Rivers (NM Portugal). Ecotoxicol Environ Saf 73(4):524–533

    Article  CAS  Google Scholar 

  • Gu C, Karthikeyan KG (2005) Interaction of tetracycline with aluminum and iron hydrous oxides. Environ Sci Technol 39(8):2660–2667

    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(22):7130–7139

    CAS  Google Scholar 

  • Halling-Sorensen B, Nielson BN, Lanzky PF, Ingerslev F, Lutzhoft HCH, Jorgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment—a review. Chemosphere 36(2):357–393

    Article  CAS  Google Scholar 

  • Halling-Sorensen B, Sengelov G, Tjornelund J (2002) Toxicity of teracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria. Arch Environ Contam Toxicol 44:7–16

    Article  Google Scholar 

  • Hawkins WE, Overstreet RM, Provancha MJ (1984) Effects of space shuttle exhaust plumes on gills of some estuarine fishes: a light and electron microscopic study. Gulf Res Rep 7(4):297–309

    Google Scholar 

  • Hirsch R, Ternes R, Haberer K, Kratz KL (1999) Occurrence of antibiotics in the aquatic environment. Sci Total Environ 225(1–2):109–118

    Article  CAS  Google Scholar 

  • Hughes GM, Perry SF (1976) Morphometric study of trout gills: a light-microscope method suitable for the evaluation of pollutant action. J Exp Biol 64:447–460

    Google Scholar 

  • Jia A, Xiao Y, Hu J, Asami M, Kunikane S (2009) Simultaneous determination of tetracyclines and their degradation products in environmental waters by liquid chromatography–electrospray tandem mass spectrometry. J Chromatogr A 1216:4655–4662

    Article  CAS  Google Scholar 

  • Jones OAH, Voulvoulis N, Lester JN (2002) Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Res 36(20):5013–5022

    Article  CAS  Google Scholar 

  • Kang JJ, Fang H (1997) Polycyclic aromatic hydrocarbons inhibit the activity of acetylcholinesterase purified from electric eel. Biochem Biophys Res Commun 238(2):367–369

    Article  CAS  Google Scholar 

  • Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW (2005) Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical scavenging activity. J Neurochem 94(3):818–827

    Article  Google Scholar 

  • Kummerer K (2009) Antibiotics in the aquatic environment—a review—part I. Chemosphere 75:417–434

    Article  Google Scholar 

  • Machado ALS, Brandão AAH, da Silva CMOM, da Rocha RF (2003) Influence of tetracycline in the hepatic and renal development of rat’s offspring. Braz Ach Biol Technol 46(1):47–51

    CAS  Google Scholar 

  • Martinez CBR, Nagae MY, Zaia CTBV, Zaia DAM (2004) Morphological and physiological acute effects of lead in the neotropical fish Prochilodus lineatus. Braz J Biol 64(4):797–807

    Article  CAS  Google Scholar 

  • Michael I, Rizzo L, McArdell CS, Manaia CM, Merlin C, Schwartz T et al (2013) Urban wastewater treatment plants as hotspots for the release of antibiotics in the environment: a review. Water Res 47(3):957–995

    Article  CAS  Google Scholar 

  • Nero V, Farwell A, Lee LEJ, Van Meer T, MacKinnon MD, Dixon DG (2006) The effects of salinity on naphthenic acid toxicity to yellow perch: gill and liver histopathology. Ecotoxicol Environ Saf 65(2):252–264

    Article  CAS  Google Scholar 

  • Nico L, Fuller P (2013) Gambusia holbrooki. USGS Nonindigenous Aquatic Species Database, Gainesville, FL. http://nas.er.usgs.gov/queries/Factsheet.aspx?speciesID=849. Accessed: May 4, 2013

  • Nunes B (2011) The use of cholinesterases in ecotoxicology. Rev Environ Contam Toxicol 212:29–59

    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 72(2):341–354

    Article  Google Scholar 

  • Olsson PE, Larsson A, Haux C (1996) Influence of seasonal changes in water temperature on cadmium inducibility of hepatic and renal metallothionein in rainbow trout. Mar Environ Res 42:41–44

    Article  CAS  Google Scholar 

  • Olurin KB, Olojo EAA, Mbaka GO, Akindele AT (2006) Histopathological responses of the gill and liver tissues of Clarias gariepinus fingerlings to the herbicide, glyphosate. AJB 5:2480–2487

    CAS  Google Scholar 

  • Organisation for Economic Co-operation and Development (1992) OECD guidelines for the testing of chemicals, Section 2-fish, early-life stage toxicity test (guideline no. 210). OECD Publishing. doi:10.1787/9789264070103-en

  • Ozmen M, Ayas Z, Gungurdu A, Ekmekci GF, Yerli S (2008) Ecotoxicological assessment of water pollution in Sariyar Dam Lake, Turkey. Ecotoxicol Environ Safe 70(1):167–173

    Article  Google Scholar 

  • Pari L, Gnanasoundari M (2006) Influence of naringenin on oxytetracyclie mediated oxidative damage in rat liver. Basic Clin Pharmacol Toxicol 98(5):456–461

    Article  CAS  Google Scholar 

  • Péry AR, Gust M, Vollat B, Mons R, Ramil M, Fink G et al (2008) Fluoxetine effects assessment on the life cycle of aquatic invertebrates. Chemosphere 73(3):300–304

    Article  Google Scholar 

  • Poleksic V, Mitrovic-Tutundzic V (1994) Fish gills as a monitor of sublethal and chronic effects of pollution. In: Müller R, Lloyd R (eds) Sublethal and chronic effects of pollutants on freshwater fish. Fishing New Books, Oxford

    Google Scholar 

  • Ramos AS, Antunes SC, Gonçalves F, Nunes B (2014) The gooseneck barnacle (Pollicipes pollicipes) as a candidate sentinel species for coastal contamination. Arch Environ Toxicol 66(317–326):1

    Google Scholar 

  • Ribeiro SHM (2012) Estimativa dos benefícios da melhoria na qualidade da água no Cértima Master thesis [in Portugese]. University of Aveiro, Portugal

  • Said AA, Matsuki N, Kasuya Y (1995) Effects of aminoglycoside antibiotics on cholinergic autonomic nervous transmission. Pharmacol Toxicol 76(2):128–132

    Article  CAS  Google Scholar 

  • Sarmah AK, Meyer MT, Boxall AB (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65(5):725–759

    Article  CAS  Google Scholar 

  • Sayed AEDH, Mekkawy IA, Mahmoud UM (2012) Histopathological alterations in some body organs of adult Clarias gariepinus (Burchell, 1822) exposed to 4-nonylphenol, zoology. In: Garcia MD (ed) zoology. InTech, West Palm Beach, pp 163–184

    Google Scholar 

  • Shabana MB, Ibrahim HM, Khadre SEM, Elemam MG (2012) Influence of rifampicin and tetracycline administration on some biochemical and histological parameters in albino rats. J Basic App Zool 65(5):299–308

    Article  CAS  Google Scholar 

  • Snavely SR, Hodges GR (1984) The neurotoxicity of antibacterial agents. Ann Intern Med 101(1):92–104

    Article  CAS  Google Scholar 

  • Soory M (2008) A role for non-antimicrobial actions of tetracyclines in combating oxidative stress in periodontal and metabolic diseases: a literature review. Open Dent J 2:5–12

    Article  CAS  Google Scholar 

  • Spilovska K, Korabecny J, Kral J, Horova A, Musilek K, Soukup O et al (2013) 7-Methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer’s disease treatment—synthesis, biological evaluation and molecular modeling studies. Molecules 18:2397–2418

    Article  CAS  Google Scholar 

  • Stentiford GD, Longshaw M, Lyons BP, Jones G, Green M, Feist SW (2003) Histopathological biomarkers in estuarine fish species for the assessment of biological effects of contaminants. Mar Environ Res 55(2):137–159

    Article  CAS  Google Scholar 

  • Stevens DE (1992) Gill morphometry of the red drum, Sciaenops ocellatus. Fish Physiol Biochem 10(2):169–176

    Article  Google Scholar 

  • Sturve J, Almroth BC, Forlin L (2008) Oxidative stress in rainbow trout (Oncorhynchus mykiss) exposed to sewage treatment plant effluent. Ecotoxicol Environ Safe 70(3):446–452

    Article  CAS  Google Scholar 

  • Temmink JHM, Bowmieister PJ, Jong P, van der Berg JHJ (1983) An ultra-structural study of chromate-induced hyperplasia in the gill of rainbow trout, Salmo gairdneri. Aquat Toxicol 4(2):165–179

    Article  CAS  Google Scholar 

  • Thomas RJ (1994) Neurotoxicity of antibacterial therapy. South Med J 87(9):869–874

    Article  CAS  Google Scholar 

  • Tu HT, Silvestre F, Scippo M-L, Thome J-P, Phuong NT, Kestemont P (2009) Acetylcholinesterase activity as a biomarker of exposure to antibiotics and pesticides in the black tiger shrimp (Penaeus monodon). Ecotoxicol Environ Saf 72(5):1463–1470

    Article  CAS  Google Scholar 

  • van den Booggard AE, Stobberingh EE (1999) Antibiotic usage in animals: impact on bacterial resistance and public health. Drugs 58(4):589–607

    Article  Google Scholar 

  • Van Dyk JC, Pieterse GM, Van Vuren JHJ (2007) Histological changes in the liver of Oreochromis mossambicus (Cichlidae) after exposure to cadmium and zinc. Ecotoxicol Environ Safe 66:432–440

    Article  Google Scholar 

  • Van Heerden D, Vosloo A, Nikinmaa M (2004) Effects of short-term, copper exposure on gill structure metallothionein and hypoxia-inducible factor-1a (HIF-1a) levels in rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 69:271–280

    Article  Google Scholar 

  • Verlicchi P, Galleti 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

    Article  CAS  Google Scholar 

  • Wang QQ, Yates SR (2008) Laboratory study of oxytetracycline degradation kinetics in animal manure and soil. J Agric Food Chem 56(5):1683–1688

    Article  CAS  Google Scholar 

  • Wilson JM, Bunte RM, Anthony J, 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):785–789

    CAS  Google Scholar 

  • Wood CM, Soivio A (1991) Environmental effects on gill function: an introduction. Physiol Zool 64:1–3

    Google Scholar 

  • Yasser AG, Naser MD (2011) Impact of pollutants on fish collected from different parts of Shatt Al-Arab River: a histopathological study. Environ Monit Assess 181(1–4):175–182

    Article  Google Scholar 

  • Yonar ME (2012) The effect of lycopene on oxytetracycline-induced oxidative stress and immunosuppression in rainbow trout (Oncorhynchus mykiss, W.). Fish Shellfish Immunol 32(6):994–1001

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the European Regional Development Fund through the COMPETE—Operational Competitiveness Program and by national funds through the Foundation for Science and Technology under the projects PEst-C/MAR/LA0015/2013 and PTDC/AMB/70431/2006.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. Nunes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 12 kb)

Supplementary material 2 (PNG 647 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nunes, B., Antunes, S.C., Gomes, R. et al. Acute Effects of Tetracycline Exposure in the Freshwater Fish Gambusia holbrooki: Antioxidant Effects, Neurotoxicity and Histological Alterations. Arch Environ Contam Toxicol 68, 371–381 (2015). https://doi.org/10.1007/s00244-014-0101-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-014-0101-z

Keywords

Navigation