Skip to main content

Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio)

Abstract

In order to assess potential effects of human pharmaceuticals in aquatic wildlife, laboratory experiments were conducted with carbamazepine, clofibric acid, metoprolol, and diclofenac using fish as test organisms. For each substance, at least one environmentally relevant concentration was tested. In liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric acid, and metoprolol, ultrastructural effects were qualitatively described and semi-quantitatively assessed. The obtained assessment values were compared with previously published data for diclofenac-induced effects in rainbow trout tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac-exposed trout corroborated previously published data which indicated that diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet degeneration of proximal kidney tubules. The investigations provided information on the general health status of the pharmaceutical-exposed fish, and allowed a differential diagnosis of harmful effects caused by these human pharmaceuticals in non-target species. For the different cytological effects observed, lowest observed effect concentration (LOECs) for at least three of the test substances (diclofenac, carbamazepine, metoprolol) were in the range of environmentally relevant concentrations (1 μg/L).

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20
Fig. 21
Fig. 22

References

  1. Apel P, Koschorreck J (2005) UBA-Texte 29/05:29–36

    Google Scholar 

  2. EMEA (2006) EMEA/CHMP/SWP/4447/00

  3. Daughton CG, Ternes TA (1999) Environ Health Perspect 107(6):907–938

    Article  CAS  Google Scholar 

  4. Sacher F (2002) Stuttg Ber Siedlungswasserwirtsch 168:59–69

    CAS  Google Scholar 

  5. Hanisch B, Abbas B, Kratz W, Schüürmann G (2004) Z Umweltchem Ökotox 16(4):223–238

    CAS  Google Scholar 

  6. Rohweder U, Friesel P (2005) UBA-Texte 29/05:115–132

    Google Scholar 

  7. Salomon M (2005) Z Umweltchem Ökotox 17(1):50–53

    CAS  Google Scholar 

  8. Heberer T, Ternes T (2006) In: Reemtsma T, Jekel M (eds) Organic pollutants in the water cycle. Wiley VCH, Weinheim

    Google Scholar 

  9. Lehmann M (2000) In: LFU Baden-Württemberg (ed) 25 Jahre LFU. Jahresbericht 1998/99

  10. Ternes T (2001) Wasser Boden 53(4):9–14

    CAS  Google Scholar 

  11. Henschel K-P, Wenzel A, Diedrich M, Fliedner A (1997) Regul Toxicol Pharmacol 25:220–225

    Article  CAS  Google Scholar 

  12. Braunbeck T, Storch V (1989) BIUZ 19(4):127–132

    Article  CAS  Google Scholar 

  13. Myers MS, Fournie JW (2002) In: Adams SM (ed) Biological indicators of aquatic ecosystem stress. Am Fish Soc, Bethesda, Maryland, pp 221–288

  14. Triebskorn R (2005) In: Lehr JH, Keeley J (eds) Water encyclopedia: water quality and resource development. ISBN: 0-471-73686-4. Wiley, NJ

    Google Scholar 

  15. Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Aquat Toxicol 68(2):141–150

    Article  CAS  Google Scholar 

  16. Braunbeck T, Völkl A (1991) Ecotox Env Saf 21:119–127

    Google Scholar 

  17. Braunbeck T, Storch V, Nagel R (1989) Aquat Toxicol 14:185–202

    Article  CAS  Google Scholar 

  18. Gernhöfer M, Müller E, Pawert M, Schramm M, Triebskorn R (2001) J Aquat Ecosyst Stress Recov 8(3/4):241–260

    Article  Google Scholar 

  19. Karnovsky MJ (1971) J Cell Biol 51:284

    Google Scholar 

  20. Reynolds ES (1963) J Cell Biol 17:208–212

    Article  CAS  Google Scholar 

  21. Gori P (1977) J Microsc 110:163–165

    CAS  Google Scholar 

  22. Triebskorn R, Köhler H-R, Honnen W, Schramm M, Adams SM, Müller EF (1997) J Aquat Ecosys Stress Recov 6:57–73

    Article  CAS  Google Scholar 

  23. Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler H-R, Schwaiger J (2004) Aquat Toxicol 68(2):151–166

    Article  CAS  Google Scholar 

  24. Sattelberger R (1999) Reports Umweltbundesamt Wien. 162:121, ISBN:385457-510-6

  25. Cheon Y, Nara TY, Band MR, Beever JE, Wallig MA, Nakamura MT (2005) Am J Physiol Regul Integr Comp Physiol 288:1525–1535

    Google Scholar 

  26. Ibabe A, Grabenbauer M, Baumgart E, Fahimi DH, Cajaraville MP (2002) Histochem Cell Biol 118(3):231–239

    CAS  Google Scholar 

  27. Gamprel A, Wilkinson M, Boutilier R (1994) Gen Comp Endocrinol 95:259–272

    Article  Google Scholar 

  28. Nickerson JG, Dugan SG, Drouin G, Moon TW (2001) Eur J Biochem 268(24):6465–6472

    Article  CAS  Google Scholar 

  29. Bauer LA, Horn JR, Maxon MS, Easterling TR, Shen DD, Strandness DE Jr (2000) J Clin Pharmacol 40:533–543

    Article  CAS  Google Scholar 

  30. Larsson DGJ, Fredriksson S, Sandblom E, Paxeus N, Axelsson M (2006) Environ Toxicol Pharmacol 22(3):338–340

    Article  CAS  Google Scholar 

  31. Fux R, Meisner C, Schwab M, Lorenz G, Mörike K, Gleiter CH (2004) Z ärztl Fortb Qual Gesundheitswesen 98(8):689–694

    Google Scholar 

  32. Laville N, Ait-Aissa S, Gomez E, Casellas C, Porcher JM (2004) Toxicol 196(1–2):41–55

    Article  CAS  Google Scholar 

  33. Vane JR (1971) Nature 231:232–235

    CAS  Google Scholar 

  34. Patrignani P, Panara MR, Santini G (1996) Prostaglandins Leukot Essent Fat Acids 55(1):115

    Article  Google Scholar 

  35. Flower RJ (1999) Rheumatol 38:693–696

    Article  CAS  Google Scholar 

  36. Hoeger B, Köllner B, Dietrich DR, Hitzfeld B (2005) Aquat Toxicol 75:53–64

    Article  CAS  Google Scholar 

  37. Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJI, Arshad M, Mahmood S, Ali A, Khan AA (2004) Nature 427:630–633

    Article  CAS  Google Scholar 

  38. Mallat J (1985) Can J Fish Aquat Sci 42:630–648

    Article  Google Scholar 

  39. Schmidt-Posthaus H, Bernet D, Wahli T, Burkhardt-Holm P (2001) Dis Aquat Org 44:161–170

    CAS  Google Scholar 

  40. Cerqueira CC, Fernandes MN (2002) Ecotoxicol Environ Saf 52(2):83–91

    Article  CAS  Google Scholar 

  41. Leino RL, McCormik JH (1984) Cell Tiss Res 236:121–128

    Article  CAS  Google Scholar 

  42. Gaberoy NB, Quinitio GF (2000) Fish Physiol Biochem 23(1):83–94

    Article  Google Scholar 

  43. Ledy K, Giamberini L, Pihan JC (2003) Dis Aquat Organ 56(3):235–240

    CAS  Google Scholar 

  44. Pawert M, Müller E, Triebskorn R (1998) Tissue Cell 30(6):617–626

    Article  CAS  Google Scholar 

  45. Ferrari B, Paxéus N, Lo Giudice R, Pollio A, Garric J (2003) Ecotoxicol Environ Saf 55:359–370

    Article  CAS  Google Scholar 

  46. Hallare AV, Köhler HR, Triebskorn R (2004) Chemosphere 56:659–666

    Article  CAS  Google Scholar 

  47. Cleuvers M (2005) Chemosphere 59:199–205

    Article  CAS  Google Scholar 

  48. Fent K, Weston AA, Caminada D (2006) Aquat Toxicol 78(2):122–159

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the Bavarian State Ministry of the Environment, Public Health, and Consumer Protection. Additional funding was provided by the Foundation of the Landesbank Baden-Württemberg “Natur und Umwelt”. Thanks are due to Heinz Köhler for critically reviewing this manuscript and for providing laboratory equipment, as well as to Oliver Betz for laboratory equipment, and to Hermann Ferling for performing the exposure experiments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Triebskorn.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Triebskorn, R., Casper, H., Scheil, V. et al. Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio). Anal Bioanal Chem 387, 1405–1416 (2007). https://doi.org/10.1007/s00216-006-1033-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-006-1033-x

Keywords