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Inhibition of hepatic sterol and squalene biosynthesis in rats fed di‐2‐ethylhexyl phthalate
Author(s) -
Bell Frank P.
Publication year - 1976
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02533053
Subject(s) - squalene , phthalate , sterol , cholesterol , chemistry , desmosterol , clinical chemistry , biosynthesis , medicine , endocrinology , biochemistry , lipidology , biology , enzyme , organic chemistry
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‐ 14 C and mevalonate‐5‐ 3 H into squalene, C 30 sterols, and C 27 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 3 H‐mevalonate conversion to squalene and sterols developed more slowly, being reduced to ca. 70% of control values in 11 days, whereas 14 C‐acetate conversion was reduced to ca. 35% of control values during the same period. 3 H‐mevalonate conversion to sterols and squalene was, however, found to be suppressable to the same extent as 14 C‐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 14 C‐acetate and 3 H‐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.