Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethylene.
A single 8-h exposure to trans-1,2-dichloroethylene (t-DCE) or cis-1,2-dichloroethylene (c-DCE) at 200 ppm (hygienic standard in workplaces) resulted in a significant increase in the hexobarbital sleeping time, the zoxazolamine paralysis time, and the metabolic formation of 4-aminoantipyrine from aminopyrine in adult female Wistar rats. Higher DCE concentrations caused a dose-dependent and substantial enhancement of these effects, the effects of c-DCE being stronger than that of t-DCE. In the course of enzyme-kinetic measurements in isolated rat liver microsomes, t-DCE proved to be a competitive inhibitor of the oxidative N-demethylation of aminopyrine and of the O-demethylation of p-nitroanisole. It is concluded from the results that the inhibition of hepatic drug metabolism is caused by a competitive and reversible interaction of the 2 DCE isomers with the mixed-function oxidase system, the interaction possibly operating at the type I binding site.
D000818:Animals; D004000:Dichloroethylenes / Q000494:pharmacology*; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010243:Paralysis / Q000139:chemically induced; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013237:Stereoisomerism; D013997:Time Factors; D015049:Zoxazolamine / Q000494:pharmacology
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D015049:Zoxazolamine; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases