title: Toxicological actions of plant-derived and anthropogenic methylenedioxyphenyl-substituted chemicals in mammals and insects.
abstract: The methylenedioxyphenyl (MDP) substituent is a structural feature present in many plant chemicals that deter foraging by predatory insects and herbivores. With increasing use of herbal extracts in alternative medicine, human exposure to MDP-derived plant chemicals may also be significant. Early studies found that most MDP agents themselves possess relatively low intrinsic toxicity, but strongly influence the actions of other xenobiotics in mammals and insects by modulating cytochrome P-450 (CYP)-dependent biotransformation. Thus, after exposure to MDP chemicals an initial phase of CYP inhibition is followed by a sustained phase of CYP induction. In insects CYP inhibition by MDP agents underlies their use as pesticide synergists, but analogous inhibition of mammalian CYP impairs the clearance of drugs and foreign compounds. Conversely, induction of mammalian CYP by MDP agents increases xenobiotic oxidation capacity. Exposure of insects to MDP-containing synergists in the environment, in the absence of coadministered pesticides, may also enhance xenobiotic detoxication. Finally, although most MDP agents are well tolerated, several, typified by safrole, aristolochic acid, and MDP-kavalactones, are associated with significant toxicities, including the risk of hepatotoxicity or tumorigenesis. Thus, the presence of MDP-substituted chemicals in the environment may produce a range of direct and indirect toxicities in target and nontarget species.
authors.affiliation: Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, New South Wales, 2006, Australia. michael.murray@sydney.edu.au
authors.forename: Michael
authors.initials: M
authors.lastname: Murray
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D052117:Benzodioxoles / Q000633:toxicity; D001593:Benzyl Compounds / Q000633:toxicity; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004148:Dioxolanes / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007313:Insecta / Q000187:drug effects*; D010574:Pesticide Synergists / Q000633:toxicity; D010944:Plants / Q000737:chemistry*; D011748:Pyrogallol / Q000031:analogs & derivatives / Q000633:toxicity; D012451:Safrole / Q000633:toxicity; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D000081248:Allylbenzene Derivatives; D052117:Benzodioxoles; D001593:Benzyl Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D004148:Dioxolanes; D004785:Environmental Pollutants; D010574:Pesticide Synergists; D015262:Xenobiotics; D011748:Pyrogallol; C005246:myristicin; D003577:Cytochrome P-450 Enzyme System; D012451:Safrole