Inhibition of hepatic sterol and squalene biosynthesis in rats fed di-i-ethylhexyl phthalate.
Di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer, was found to be an inhibitor of the biosynthesis of hepatic nonsaponifiable lipids in the art. The addition of DEHP at levels of 0.5% or 1.0% to a stock diet of rats resulted in a decreased conversion of acetate-1-14C and mevalonate-5-3H into squalene, C30 sterols, and C27 sterols by liver minces or slices, in vitro. In studies conducted with 0.5% DEHP feeding from 2 to 11 days, the degree of inhibition was found to increase with the duration of DEHP feeding; the inhibition of 3H-mevalonate conversion to squalene and sterols developed more slowly, being reduced to ca. 70% control values in 11 days, whereas 14C-acetate conversion was reduced to ca. 35% of control values during the same period. 3H-mevalonate conversion to sterols and squalene was, however, found to be suppressable to the same extent as 14C-acetate conversion when diets containing 1.0% DEHP were fed for 18 days. The inhibitory effect of dietary DEHP on sterol and squalene biosynthesis from 14C-acetate and 3H-mevalonate by rat liver preparations is unlikely to be accounted for by the negative feedback of cholesterol secondary to hepatic sterol accumulation since, in these studies, hepatic total lipid and hepatic total sterol levels were similar in control and DEHP-fed rats.
D000085:Acetates / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D010795:Phthalic Acids / Q000494:pharmacology*; D051381:Rats; D013185:Squalene / Q000096:biosynthesis*; D013261:Sterols / Q000096:biosynthesis*; D013997:Time Factors
D000085:Acetates; D010795:Phthalic Acids; D013261:Sterols; D013185:Squalene; D004051:Diethylhexyl Phthalate; D008798:Mevalonic Acid