Effects of marine biotoxins on drug-metabolizing cytochrome P450 enzymes and their regulation in mammalian cells.

ABSTRACT

Marine biotoxins are a heterogenous group of natural toxins, which are able to trigger different types of toxicological responses in animals and humans. Health effects arising from exposure to marine biotoxins are ranging, for example, from gastrointestinal symptoms to neurological effects, depending on the individual toxin(s) ingested. Recent research has shown that the marine biotoxin okadaic acid (OA) can strongly diminish the expression of drug-metabolizing cytochrome P450 (CYP) enzymes in human liver cells by a mechanism involving proinflammatory signaling. By doing so, OA may interfere with the metabolic barrier function of liver and intestine, and thus alter the toxico- or pharmacokinetic properties of other compounds. Such effects of marine biotoxins on drug and xenobiotic metabolism have, however, not been much in the focus of research yet. In this review, we present the current knowledge on the effects of marine biotoxins on CYP enzymes in mammalian cells. In addition, the role of CYP-regulating nuclear receptors as well as inflammatory signaling in the regulation of CYPs by marine biotoxins is discussed. Strong evidence is available for effects of OA on CYP enzymes, along with information about possible molecular mechanisms. For other marine biotoxins, knowledge on effects on drug metabolism, however, is scarce.