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 (o5 mmol (1 mg)/kg) or via water (o50 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 35710nM for rainbow trout, 47717nM for turbot, and 111770nM for Atlantic cod. These observed effects suggest that medetomidine interferes with CYP1A-dependent metabolism of xenobiotics in these fish species.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Ekologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Ecology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Zoologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Zoology (hsv//eng)

Nyckelord

Medetomidine; Imidazole; a2-Adrenoceptor agonist; CYP1A; EROD; Antifouling; Fish

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