The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal): evaluation of impacts on fish liver, by histopathology, stereology, vitellogenin and CYP1A immunohistochemistry, after sub-acute exposures of the zebrafish model

Environ Toxicol Pharmacol. 2012 Jul;34(1):34-45. doi: 10.1016/j.etap.2012.02.007. Epub 2012 Mar 3.


Qualitative and quantitative approaches were tested to assess zebrafish liver effects after sub-acute exposures of certain pharmaceuticals. Carbamazepine, fenofibric acid, propranolol, sulfamethoxazole and trimethoprim were tested individually and in mixtures, including low environmental levels. Overall, data showed sex specific reactions in liver, with the major alterations being observed in males. Males treated with propranolol, fenofibric acid and with mixtures, showed an increase of vitellogenin immunostaining, compared with the control. Males also evidenced a tendency for an increased hepatic mass, after individual and mixture exposures. The volume-weighted nuclear volume of hepatocytes was high in males after exposures to either mixture, which together with the greater cytoplasmic eosinophilia and changes in cytochrome P450 1A immunoreactivity, point to an increase in metabolic/detoxification activity. These investigations revealed distinct impacts depending on the exposure type, and strengthened the importance of studying non-steroidal compounds in mixtures, including environmental levels and both sexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbamazepine / toxicity
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Fenofibrate / analogs & derivatives
  • Fenofibrate / toxicity
  • Fish Proteins / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Portugal
  • Propranolol / toxicity
  • Rivers
  • Sulfamethoxazole / toxicity
  • Trimethoprim / toxicity
  • Vitellogenins / metabolism
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish


  • Fish Proteins
  • Vitellogenins
  • Water Pollutants, Chemical
  • Carbamazepine
  • Propranolol
  • Trimethoprim
  • fenofibric acid
  • Cytochrome P-450 CYP1A1
  • Sulfamethoxazole
  • Fenofibrate