The natural basil flavonoid nevadensin protects against a methyleugenol-induced marker of hepatocarcinogenicity in male F344 rat

•Co-exposure to nevadensin inhibited formation of methyleugenol DNA adducts in the liver of male F344 rat.•Co-exposure to nevadensin inhibited formation of hepatocellular altered foci (HAF) in the liver of male F344 rat.•The nevadensin-mediated reduction in formation of methyleugenol DNA adducts was comparable to reduction in levels of HAF.•The adverse effects of methyleugenol in rodent bioassays may be lower when testing basil instead of pure methyleugenol. The alkenylbenzene methyleugenol occurs naturally in a variety of spices and herbs, including basil, and their essential oils. At high dose levels methyleugenol induces hepatocarcinogenicity in rodents following bioactivation to 1′-sulfooxymethyleugenol which forms DNA adducts. This study investigated whether the inhibitory effect of the basil flavonoid nevadensin on sulfotransferase (SULT)-mediated bioactivation of methyleugenol observed in vitro would also be reflected in a reduction of DNA adduct formation and a reduction in an early marker for liver carcinogenesis in an 8-week rat study. Co-exposure to methyleugenol and nevadensin orally resulted in a significant inhibition of liver methyleugenol DNA adduct formation and in inhibition of hepatocellular altered foci induction, representing indicators for initiation of neoplasia. These results suggest that tumor formation could be lower in rodent bioassays when methyleugenol would be dosed in a matrix containing SULT inhibitors such as nevadensin compared to experiments using the pure methyleugenol.