Interaction of styrene and acetone with drug biotransformation enzymes in rat liver.
In the presence of hepatic microsomes, styrene produced a type I difference spectrum, which demonstrates that styrene binds to the catalytic site of ferricytochrome P-450. A comparison of the binding parameters for the interaction of styrene with noninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes indicated that styrene is predominantly bound by cytochrome P-450 and not by cytochrome P-448. Inhalation exposure to a mixture of acetone (1,000 ppm, 6 h/d) and styrene (300 ppm, 6 h/d) for 5 d caused a distinct decrease in hepatic free nonprotein sulfhydryl groups. This decrease could be observed both with and without phenobarbital treatment. Acetone inhalation alone also enhanced ethoxycoumarin O-deethylase activity in rats without pretreatments. Acetone inhalation also increased the cytochrome P-450 content of liver microsomes, but it had no effect on NADPH cytochrome c reductase or epoxide hydratase activity. Combined exposure to styrene and acetone enhanced NADPH cytochrome c reductase activity in nonphenobarbital-treated rats, but no effect was seen in the phenobarbital-treated animals. Phenobarbital treatment of animals can greatly modify the biotransformation and toxicity of styrene, phenobarbital inducible P-450 hemoprotein playing a predominant role in its metabolism. Simultaneous inhalation exposure to acetone also interacts with the metabolism of styrene.
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013343:Styrenes / Q000008:administration & dosage / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013343:Styrenes; D013438:Sulfhydryl Compounds; D000096:Acetone; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D010634:Phenobarbital