Investigations on the mechanism of the hypocholesterolemic action of diethylhexyl phthalate in rats

Abstract

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.