Phthalate esters: Effects of orally administered dibutylphthalate on cytochrome P-450 mediated metabolism in rat liver and lung

Walseth, F; Nilsen, OG

HERO ID

684038

Reference Type

Journal Article

Year

1986

Language

English

PMID

3099543

HERO ID 684038
In Press No
Year 1986
Title Phthalate esters: Effects of orally administered dibutylphthalate on cytochrome P-450 mediated metabolism in rat liver and lung
Authors Walseth, F; Nilsen, OG
Journal Acta Pharmacologica et Toxicologica
Volume 59
Issue 4
Page Numbers 263-269
Abstract Dibutylphthalate (DBP) was administered to male Sprague Dawley rats in oral doses of 0.01, 0.1 and 1.0 mmol/kg for five days. The lower dose was considered relevant to human intake. Additional groups were given a recovery period of four weeks without DBP. DBP significantly increased the liver microsomal concentration of cytochrome P-450 (48%) at the lowest dose and NADPH-cytochrome-c-reductase activity (28-29%), at the two lower doses. The liver microsomal metabolism of n-hexane increased to about the same extent at all dosage levels. The main increase was found in the formation of the preneurotoxic metabolite 2-hexanol. The induction of cytochrome P-450 and NADPH-cytochrome-c-reductase in liver microsomes did not return to normal after the period of recovery, whereas the metabolism of n-hexane normalized during the same period of time, indicating that the majority of the induced forms of cytochrome P-450 were not related to n-hexane metabolism. No major changes were observed in the liver microsomal metabolism of B(a)P. The only effect found in cytochrome P-450 related metabolism in lung microsomes was a decrease of the B(a)P metabolism, especially in the formation of the 9,10- and 4,5-diol metabolites at lower dosage levels. It is suggested that DBP and its hydrolyzed products formed in the intestine after oral administration exert the same effect on some specific forms of cytochrome P-450 in liver and lung. It is concluded that DBP is a moderate to weak inducer of several minor forms of liver microsomal cytochrome P-450 enzymes in doses which may be relevant to human oral intake.
Doi 10.1111/j.1600-0773.1986.tb00167.x
Pmid 3099543
Wosid WOS:A1986E830200003
Is Certified Translation No
Dupe Override No
Comments Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0022977019&doi=10.1111%2fj.1600-0773.1986.tb00167.x&partnerID=40&md5=07b5616428d00b17f338cced04cab834
Is Public Yes
Language Text English
Keyword Dibutyl phthalate; oral administration; rat; enzymatic activities; liver; lung
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