Cocktail effects on fish biomarkers

• Chemicals with different modes-of-action can share common routes for their metabolism and excretion. A chemical’s toxicity and biological half-life can be altered in mixtures as a result of toxicokinetic interactions and these interactions can also interfere with biomarker responses. Two common biomarkers; induction of CYP1A, via AhR activation, and induction of vitellogenin, via ER activation, can be affected by exposures to mixtures. There are different types of cocktail effects that can affect these biomarker responses and hence can result in either overestimation or underestimation of the exposure. For example, exposure to chemicals that can act as inhibitors of catabolic CYP enzymes (CYP1-4) and efflux pumps (ABC-transporters) can result in decreased elimination of other chemicals. Reduced elimination of AhR agonists results in increased induction of CYP1A and leads to overestimation of the exposure to AhR agonists. Inhibition receptor cross-talk can also interfere with biomarker responses. For example, exposure to AhR agonists that activate AhR signaling can result in decreased ER signaling. This results in decreased induction of vitellogenin and leads to underestimation of the actual exposure. To address the possible involvement of toxicokinetic interactions and receptor cross-talks, we need to combine analyses on receptor signaling with studies on functions of key detoxification mechanisms.

Ämnesord

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

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

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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

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

Nyckelord

mixture toxicity

pharmaceuticals

biotransformation

efflux

nuclera receptors

cytochrome P450

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