Benoxaprofen suppression of polychlorinated biphenyl toxicity without alteration of mixed function oxidase function.
Polyhalogenated hydrocarbons are widely distributed environmental pollutants. Several members of the class, including certain polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans and dibenzodioxins, produce a characteristic toxicity syndrome, manifestations of which are increased mortality, oedema, hyperkeratosis, thymic involution and hepatotoxicity. The toxic hydrocarbons are also inducers of cytochrome P448-mediated mixed function oxidases. The toxicity and induction responses both involve initial binding of the hydrocarbon to the same cytosolic receptor, but the subsequent events are not understood. It is not known, for example, whether the toxicity and induction are causally related, or whether they are coordinated but independent aspects of a pleiotropic response. Here we report that benoxaprofen, a nonsteroidal antiinflammatory agent, decreases the toxicity of a PCB isomer, 3,4,3',4' tetrachlorobiphenyl (TCB), in the chick embryo and that it does so without altering the degree of mixed function oxidase induction. The independent alteration of PCB toxicity and induction suggests that the two phenomena are not causally related. The decrease in toxicity by benoxaprofen suggests further that products of arachidonic acid metabolism or other mediators of inflammation may have a causal role in halogenated hydrocarbon toxicity.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002642:Chick Embryo / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1; D004336:Drug Antagonism; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011422:Propionates / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D011422:Propionates; C011677:benoxaprofen; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D007213:Indomethacin