Analytical and Bioanalytical Chemistry

, Volume 387, Issue 4, pp 1405–1416 | Cite as

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

  • R. TriebskornEmail author
  • H. Casper
  • V. Scheil
  • J. Schwaiger
Original Paper


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).


Pharmaceuticals Liver Gills Kidney Trout Carp 



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.


  1. 1.
    Apel P, Koschorreck J (2005) UBA-Texte 29/05:29–36Google Scholar
  2. 2.
    EMEA (2006) EMEA/CHMP/SWP/4447/00Google Scholar
  3. 3.
    Daughton CG, Ternes TA (1999) Environ Health Perspect 107(6):907–938CrossRefGoogle Scholar
  4. 4.
    Sacher F (2002) Stuttg Ber Siedlungswasserwirtsch 168:59–69Google Scholar
  5. 5.
    Hanisch B, Abbas B, Kratz W, Schüürmann G (2004) Z Umweltchem Ökotox 16(4):223–238Google Scholar
  6. 6.
    Rohweder U, Friesel P (2005) UBA-Texte 29/05:115–132Google Scholar
  7. 7.
    Salomon M (2005) Z Umweltchem Ökotox 17(1):50–53Google Scholar
  8. 8.
    Heberer T, Ternes T (2006) In: Reemtsma T, Jekel M (eds) Organic pollutants in the water cycle. Wiley VCH, WeinheimGoogle Scholar
  9. 9.
    Lehmann M (2000) In: LFU Baden-Württemberg (ed) 25 Jahre LFU. Jahresbericht 1998/99Google Scholar
  10. 10.
    Ternes T (2001) Wasser Boden 53(4):9–14Google Scholar
  11. 11.
    Henschel K-P, Wenzel A, Diedrich M, Fliedner A (1997) Regul Toxicol Pharmacol 25:220–225CrossRefGoogle Scholar
  12. 12.
    Braunbeck T, Storch V (1989) BIUZ 19(4):127–132CrossRefGoogle Scholar
  13. 13.
    Myers MS, Fournie JW (2002) In: Adams SM (ed) Biological indicators of aquatic ecosystem stress. Am Fish Soc, Bethesda, Maryland, pp 221–288Google Scholar
  14. 14.
    Triebskorn R (2005) In: Lehr JH, Keeley J (eds) Water encyclopedia: water quality and resource development. ISBN: 0-471-73686-4. Wiley, NJGoogle Scholar
  15. 15.
    Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Aquat Toxicol 68(2):141–150CrossRefGoogle Scholar
  16. 16.
    Braunbeck T, Völkl A (1991) Ecotox Env Saf 21:119–127Google Scholar
  17. 17.
    Braunbeck T, Storch V, Nagel R (1989) Aquat Toxicol 14:185–202CrossRefGoogle Scholar
  18. 18.
    Gernhöfer M, Müller E, Pawert M, Schramm M, Triebskorn R (2001) J Aquat Ecosyst Stress Recov 8(3/4):241–260CrossRefGoogle Scholar
  19. 19.
    Karnovsky MJ (1971) J Cell Biol 51:284Google Scholar
  20. 20.
    Reynolds ES (1963) J Cell Biol 17:208–212CrossRefGoogle Scholar
  21. 21.
    Gori P (1977) J Microsc 110:163–165Google Scholar
  22. 22.
    Triebskorn R, Köhler H-R, Honnen W, Schramm M, Adams SM, Müller EF (1997) J Aquat Ecosys Stress Recov 6:57–73CrossRefGoogle Scholar
  23. 23.
    Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler H-R, Schwaiger J (2004) Aquat Toxicol 68(2):151–166CrossRefGoogle Scholar
  24. 24.
    Sattelberger R (1999) Reports Umweltbundesamt Wien. 162:121, ISBN:385457-510-6Google Scholar
  25. 25.
    Cheon Y, Nara TY, Band MR, Beever JE, Wallig MA, Nakamura MT (2005) Am J Physiol Regul Integr Comp Physiol 288:1525–1535Google Scholar
  26. 26.
    Ibabe A, Grabenbauer M, Baumgart E, Fahimi DH, Cajaraville MP (2002) Histochem Cell Biol 118(3):231–239Google Scholar
  27. 27.
    Gamprel A, Wilkinson M, Boutilier R (1994) Gen Comp Endocrinol 95:259–272CrossRefGoogle Scholar
  28. 28.
    Nickerson JG, Dugan SG, Drouin G, Moon TW (2001) Eur J Biochem 268(24):6465–6472CrossRefGoogle Scholar
  29. 29.
    Bauer LA, Horn JR, Maxon MS, Easterling TR, Shen DD, Strandness DE Jr (2000) J Clin Pharmacol 40:533–543CrossRefGoogle Scholar
  30. 30.
    Larsson DGJ, Fredriksson S, Sandblom E, Paxeus N, Axelsson M (2006) Environ Toxicol Pharmacol 22(3):338–340CrossRefGoogle Scholar
  31. 31.
    Fux R, Meisner C, Schwab M, Lorenz G, Mörike K, Gleiter CH (2004) Z ärztl Fortb Qual Gesundheitswesen 98(8):689–694Google Scholar
  32. 32.
    Laville N, Ait-Aissa S, Gomez E, Casellas C, Porcher JM (2004) Toxicol 196(1–2):41–55CrossRefGoogle Scholar
  33. 33.
    Vane JR (1971) Nature 231:232–235Google Scholar
  34. 34.
    Patrignani P, Panara MR, Santini G (1996) Prostaglandins Leukot Essent Fat Acids 55(1):115CrossRefGoogle Scholar
  35. 35.
    Flower RJ (1999) Rheumatol 38:693–696CrossRefGoogle Scholar
  36. 36.
    Hoeger B, Köllner B, Dietrich DR, Hitzfeld B (2005) Aquat Toxicol 75:53–64CrossRefGoogle Scholar
  37. 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 427:630–633CrossRefGoogle Scholar
  38. 38.
    Mallat J (1985) Can J Fish Aquat Sci 42:630–648CrossRefGoogle Scholar
  39. 39.
    Schmidt-Posthaus H, Bernet D, Wahli T, Burkhardt-Holm P (2001) Dis Aquat Org 44:161–170Google Scholar
  40. 40.
    Cerqueira CC, Fernandes MN (2002) Ecotoxicol Environ Saf 52(2):83–91CrossRefGoogle Scholar
  41. 41.
    Leino RL, McCormik JH (1984) Cell Tiss Res 236:121–128CrossRefGoogle Scholar
  42. 42.
    Gaberoy NB, Quinitio GF (2000) Fish Physiol Biochem 23(1):83–94CrossRefGoogle Scholar
  43. 43.
    Ledy K, Giamberini L, Pihan JC (2003) Dis Aquat Organ 56(3):235–240Google Scholar
  44. 44.
    Pawert M, Müller E, Triebskorn R (1998) Tissue Cell 30(6):617–626CrossRefGoogle Scholar
  45. 45.
    Ferrari B, Paxéus N, Lo Giudice R, Pollio A, Garric J (2003) Ecotoxicol Environ Saf 55:359–370CrossRefGoogle Scholar
  46. 46.
    Hallare AV, Köhler HR, Triebskorn R (2004) Chemosphere 56:659–666CrossRefGoogle Scholar
  47. 47.
    Cleuvers M (2005) Chemosphere 59:199–205CrossRefGoogle Scholar
  48. 48.
    Fent K, Weston AA, Caminada D (2006) Aquat Toxicol 78(2):122–159CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • R. Triebskorn
    • 1
    • 2
    Email author
  • H. Casper
    • 2
  • V. Scheil
    • 1
    • 2
  • J. Schwaiger
    • 3
  1. 1.Steinbeis-Transfer Center for Ecotoxicology and EcophysiologyRottenburgGermany
  2. 2.Animal Physiological EcologyUniversity of TübingenTübingenGermany
  3. 3.Aquatic Toxicology and PathologyBavarian Environmental AgencyWielenbachGermany

Personalised recommendations