Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.

The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction...

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Main Authors: Lake, B G, Gray, T J, Gangolli, S D
Format: Online
Language:English
Published: 1986
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474416/
id pubmed-1474416
recordtype oai_dc
spelling pubmed-14744162006-06-09 Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations. Lake, B G Gray, T J Gangolli, S D Research Article The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction of the specific peroxisomal marker KCN-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. These effects could be reproduced in vivo, and potency differences were also observed between di(2-ethylhexyl) phthalate (DEHP) and its straight-chain isomer, di-n-octyl phthalate. In in vivo studies, DEHP, mono(2-ethylhexyl) phthalate, and clofibrate/clofibric acid produced large increases in liver size and peroxisomal enzyme activities in Sprague-Dawley rats and Chinese hamsters, but had less effect in Syrian hamsters. These effects could be largely reproduced in vitro where good responses were obtained with rat and Chinese hamster hepatocytes, but either little or no effect with Syrian hamster and Dunkin-Hartley guinea pig hepatocytes. Both DEHP and clofibrate appeared to induce similar form(s) of microsomal cytochrome P-450 which exhibited a high specificity towards lauric acid hydroxylation. With a range of hypolipidemic agents, including phthalate monoesters, a good correlation was observed between the induction of peroxisomal and microsomal enzyme activities in rat hepatocyte cultures. These results thus demonstrate a good relationship between the in vivo and in vitro effects of phthalate esters and related compounds and suggest that hepatocyte cultures may be useful for further studies on the hepatic effects of peroxisome proliferators. 1986-08 /pmc/articles/PMC1474416/ /pubmed/3757955 Text en
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Lake, B G
Gray, T J
Gangolli, S D
spellingShingle Lake, B G
Gray, T J
Gangolli, S D
Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
author_facet Lake, B G
Gray, T J
Gangolli, S D
author_sort Lake, B G
title Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
title_short Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
title_full Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
title_fullStr Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
title_full_unstemmed Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
title_sort hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.
description The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction of the specific peroxisomal marker KCN-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. These effects could be reproduced in vivo, and potency differences were also observed between di(2-ethylhexyl) phthalate (DEHP) and its straight-chain isomer, di-n-octyl phthalate. In in vivo studies, DEHP, mono(2-ethylhexyl) phthalate, and clofibrate/clofibric acid produced large increases in liver size and peroxisomal enzyme activities in Sprague-Dawley rats and Chinese hamsters, but had less effect in Syrian hamsters. These effects could be largely reproduced in vitro where good responses were obtained with rat and Chinese hamster hepatocytes, but either little or no effect with Syrian hamster and Dunkin-Hartley guinea pig hepatocytes. Both DEHP and clofibrate appeared to induce similar form(s) of microsomal cytochrome P-450 which exhibited a high specificity towards lauric acid hydroxylation. With a range of hypolipidemic agents, including phthalate monoesters, a good correlation was observed between the induction of peroxisomal and microsomal enzyme activities in rat hepatocyte cultures. These results thus demonstrate a good relationship between the in vivo and in vitro effects of phthalate esters and related compounds and suggest that hepatocyte cultures may be useful for further studies on the hepatic effects of peroxisome proliferators.
publishDate 1986
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474416/
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