Resveratrol affects CYP1A expression in rainbow trout hepatocytes

Resveratrol (RVT), a polyphenolic phytoalexin found in a variety of food products, including grapes and peanuts, is a well-characterized aryl hydrocarbon receptor (AhR) antagonist in mammalian cell lines. The lack of a reliable tool to block AhR signaling in rainbow trout (Oncorhynchus mykiss) prompted this study to evaluate the utility of RVT as an AhR antagonist in a piscine system. Trout hepatocytes in primary culture were exposed to varying doses of RVT (10(-5)-10(-12) M) either in the presence or absence of a well-established AhR agonist, beta-naphthoflavone (BNF). Indeed, BNF significantly elevated CYP1A and AhR protein expression in trout hepatocytes, and this response was inhibited at high (10(-5)-10(-7) M), but not low (10(-8)-10(-10) M), RVT doses. However, RVT alone at low doses (10(-8)-10(-10) M) significantly elevated CYP1A protein expression compared to control hepatocytes. This higher protein response with RVT was completely abolished with actinomycin D and cycloheximide suggesting transcriptional and translational regulation of CYP1A induction. Also, RVT at low (10(-9) M), but not high (10(-5) M), dose significantly elevated CYP1A1 mRNA transcript levels in BNF-primed hepatocytes supporting transcriptional modulation. Taken together, RVT is an effective AhR antagonist, but induces CYP1A expression at lower doses (< 10(-8) M) in trout hepatocytes. (c) 2006 Elsevier B.V All rights reserved.