Inhibition of hepatic sterol and squalene biosynthesis in rats fed di‐2‐ethylhexyl phthalate

Publisher Website
Google Scholar
Abstract
Di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer, was found to be an inhibitor of the biosynthesis of hepatic nonsaponifiable lipids in the rat. 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 of3H-mevalonate conversion to squalene and sterols developed more slowly, being reduced to ca. 70% of control values in 11 days, whereas14C-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 as14C-acetate conversion when diets containing 1.0% DEHP were fed for 18 days. The inhibitory effect of dietary DEHP on sterol and squalene biosynthesis from14C-acetate and3H-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 simialr in control and DEHP-fed rats.

This publication has 28 references indexed in Scilit: