Induction of xenobiotic-metabolizing enzymes and peroxisome proliferation in rat liver caused by dietary exposure to di(2-ethylhexyl)phosphate.
Exposure of rats to 1% or 3% (w/w) di(2-ethylhexyl)phosphate in the diet for five days results in two- to three-fold inductions of liver cytosolic epoxide hydrolase activity and microsomal cytochrome P-450 content. Cytochromes P-450b + e were induced 20- to 35-fold, but no increase was observed in cytochrome P-450c. Considerably smaller effects were obtained on NADPH-cytochrome c reductase, microsomal epoxide hydrolase and microsomal cytochrome b5 content, and there was no effect on cytosolic glutathione transferase activity, under the same conditions. A dramatic increase in cyanide-insensitive palmitoyl-CoA oxidation and total mitochondrial protein, together with smaller increases in total catalase and cytochrome oxidase activities, were observed after treatment with di(2-ethylhexyl)phosphate, indicating that this compound causes proliferation of both peroxisomes and mitochondria. It is suggested that the induction of cytosolic epoxide hydrolase and the proliferation of peroxisomes may be related processes.
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004032:Diet; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis; D010755:Organophosphates / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010755:Organophosphates; D009943:Organophosphorus Compounds; D010171:Palmitoyl Coenzyme A; C007377:di-2-(ethylhexyl)phosphoric acid; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase