Investigations on the mechanism of the hypocholesterolemic action of diethylhexyl phthalate in rats.
The plasticizer di(2-ethylhexyl)phthalate (DEHP), used widely in the manufacture of food packages and medical plastic devices, depressed serum cholesterol (40%) and proliferated hepatic mitochondria (100%) when administered in the diet (2%, w/w) to the rat. Microsomes isolated from the livers of animals administered DEHP showed lowered specific activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (50%). The incorporation of acetate but not of mevalonate into hepatic cholesterol was decreased (52%) in these animals. The release of bile acids was greatly enhanced (100%), and the activity of cholesterol 7 alpha-hydroxylase, the regulatory enzyme in the pathway of bile acid formation, was stimulated (70%) on DEHP administration. Even though the capacity of mitochondria to oxidize the side chain of cholesterol was not enhanced in DEHP-fed animals, the larger population of mitochondria would ensure that the amount of cholesterol oxidized per gram of liver was significantly higher.
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010795:Phthalic Acids / Q000494:pharmacology*; D051381:Rats
D000085:Acetates; D000924:Anticholesteremic Agents; D010795:Phthalic Acids; D002784:Cholesterol; D004051:Diethylhexyl Phthalate; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D019342:Acetic Acid; D008798:Mevalonic Acid