Metabolism of the polycyclic musk galaxolide and its interference with endogenous and xenobiotic metabolizing enzymes in the European sea bass (Dicentrarchus labrax)

Environ Pollut. 2013 Mar:174:214-21. doi: 10.1016/j.envpol.2012.11.033. Epub 2012 Dec 27.

Abstract

This study investigates the metabolism and mode of action of galaxolide (HHCB) in the European sea bass -Dicentrarchus labrax- following a single intraperitoneal injection of 50 mg HHCB/kg body weight. In addition, a group of fish was injected with 50 mg/kg of ketoconazole (KCZ), a fungicide that is known to interfere with different Cyp isoenzymes. HHCB was actively metabolised by sea bass and acted as a weak inhibitor of the synthesis of oxyandrogens in gonads of male fish. Both, HHCB and a hydroxylated metabolite were detected in bile. The fungicide ketoconazole was a strong inhibitor of Cyp11β and Cyp3a-catalyzed activities. The work contributes to the better understanding of the impact of synthetic musks on fish and proposes the determination of HHCB and/or its hydroxylated metabolite in bile as a tool to assess environmental exposure in wild fish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone / metabolism
  • Androstenedione / metabolism
  • Animals
  • Bass
  • Benzopyrans / toxicity*
  • Bile / enzymology
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP3A / metabolism
  • Endocrine Disruptors / toxicity*
  • Fatty Acids, Monounsaturated / toxicity*
  • Female
  • Glucuronosyltransferase / metabolism
  • Gonads / enzymology
  • Inactivation, Metabolic / physiology*
  • Ketoconazole / toxicity
  • Liver / enzymology
  • Male
  • Water Pollutants, Chemical / toxicity*

Substances

  • Benzopyrans
  • Endocrine Disruptors
  • Fatty Acids, Monounsaturated
  • Water Pollutants, Chemical
  • musk
  • galaxolide
  • Androstenedione
  • 17-alpha-Hydroxyprogesterone
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP3A
  • Glucuronosyltransferase
  • Ketoconazole