Biphasic responses in synergistic interactions.
Synergistic reactions, as exemplified by the methylenedioxyphenyl (benzodioxole) insecticide synergists, are one of the more studied interactions between toxicants. This group of chemicals includes, in addition to synergists such as piperonyl butoxide, carcinogens such as safrole and isosafrole and many compounds occurring naturally in foods, such as myristicin and piperine. These compounds may function as cytochrome P450 substrates, inhibitors and/or inducers. The biphasic curve in cytochrome P450 activities following a single dose is the result of an initial inhibitory phase followed by a phase of induction, with an eventual return to baseline levels. Both inhibition and induction may be isozyme-specific and different isozymes may be involved in the two activities of the same chemical. Details of these activities are presented and their significance is discussed.
Hodgson
E
E
Department of Toxicology, North Carolina State University, Raleigh 27695-7633, USA.
Ryu
D Y
DY
Adams
N
N
Levi
P E
PE
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction; D007306:Insecticides / Q000494:pharmacology; D051379:Mice; D008861:Microsomes; D008862:Microsomes, Liver / Q000378:metabolism; D010574:Pesticide Synergists / Q000494:pharmacology*; D010702:Phorate / Q000494:pharmacology; D015262:Xenobiotics / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004149:Dioxoles; D007306:Insecticides; D010574:Pesticide Synergists; D015262:Xenobiotics; D010702:Phorate; D003577:Cytochrome P-450 Enzyme System