Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethylene.

Abstract

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.

• Authors: K J Freundt, J Macholz
• Journal: Toxicology (Toxicology) Vol. 10 Issue 2 Pg. 131-9 (Jun 1978) ISSN: 0300-483X [Print] Ireland
• PMID: 684758 (Publication Type: Journal Article)

Chemical References

• Dichloroethylenes
• Hydrocarbons, Chlorinated
• Zoxazolamine
• Hexobarbital
• Mixed Function Oxygenases
• Oxidoreductases

Topics

• Animals
• Dichloroethylenes (pharmacology)
• Female
• Hexobarbital (pharmacology)
• Hydrocarbons, Chlorinated (pharmacology)
• In Vitro Techniques
• Kinetics
• Liver (enzymology)
• Microsomes, Liver (enzymology)
• Mixed Function Oxygenases (antagonists & inhibitors)
• Oxidoreductases (antagonists & inhibitors)
• Paralysis (chemically induced)
• Rats
• Sleep (drug effects)
• Stereoisomerism
• Time Factors
• Zoxazolamine (pharmacology)