Effects of medetomidine on hepatic EROD activity in three species of fish

Medetomidine, an antifouling candidate, was investigated for its effects on cytochrome P4501A (CYP1A) activity in fish. Rainbow trout (Oncorhynchus mykiss), turbot (Psetta maxima), and Atlantic cod (Gadus morhua) were exposed to medetomidine either via i.p. injection (<5 μmol (1 mg)/kg) or via water (<50 nM). Enzyme activity was measured as ethoxyresorufin-O-deethylase (EROD) activity in liver microsomes. There was a small (2–7-fold) increase in EROD activity in rainbow trout. In turbot, EROD activity increased (4-fold) after injection, while a non-significant (50%) decrease was observed after water exposure. No effects on EROD activities were observed in Atlantic cod. In vitro inhibition studies of EROD activities in liver microsomes from all three species showed that medetomidine was a very potent CYP1A inhibitor. Thus, median inhibition values (IC50) were 35±10 nM for rainbow trout, 47±17 nM for turbot, and 111±70 nM for Atlantic cod. These observed effects suggest that medetomidine interferes with CYP1A-dependent metabolism of xenobiotics in these fish species.