Hepatic cytochrome P-450-dependent metabolism and enzymatic conjugation of foreign compounds in vitamin A-deficient rats.

Abstract:

:The temporal effects of vitamin A deficiency on hepatic cytochrome P-450-dependent and conjugation reactions were studied in the rat. Cytochrome P-450 levels and N-methyl-p-chloroaniline N-demethylase activity were significantly reduced in the deficient animals. No other changes in parameters dependent on cytochrome P-450 were observed in vitro. Decreases in hepatic cytochrome P-450 were accompanied by a prolongation in hexobarbital sleeping times in deficient animals. The p-aminobenzoic acid N-acetyltransferase activity was higher in the deficient animals at 8 weeks, but by 10 weeks the activity in fact was significantly lower as compared to controls. Activities of 'native' and UDP N-acetylglucosamine 'activated' UDP-glucuronyltransferase were reduced in vitamin A deficiency. In contrast to this general pattern of impaired drug metabolism in vitamin A deficiency, glutathione S-aryltransferase activity was markedly enhanced at all time points from 4 to 10 weeks. Activities of this enzyme were twice controls at 6 weeks, a time at which no other enzyme changes were observed.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Siddik ZH,Drew R,Litterst CL,Mimnaugh EG,Sikic BI,Gram TE

doi

10.1159/000137457

subject

Has Abstract

pub_date

1980-01-01 00:00:00

pages

383-90

issue

6

eissn

0031-7012

issn

1423-0313

journal_volume

21

pub_type

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