Yonsei Med J.  1986 Jun;27(2):106-113. 10.3349/ymj.1986.27.2.106.

Enhancement of O-dealkylation in Mouse Liver by Dietary Administrations of BHA and BHT: Studies with Isolated Perfused Livers and Hepatic Microsomes

• Ji SC
• Conway JG
• Thurman RG
• Cha YN

• KMID: 693021
• DOI: http://doi.org/10.3349/ymj.1986.27.2.106

Abstract

Effects of feeding 2(3)-tert-butyl 4-hydroxyanisole (BHA) and 3, 5-di-tert-butyl 4-hydroxytoluene (BHT) on the rates of mixed function oxidation and conjugation enzyme reactions have been determined using isolated hepatic microsomal fractions and isolated perfused livers of mice. The treatments with either of the antioxidants have increased the rates of O-demethylation for p-nitroanisole and of O-deethylation for 7-ethoxycoumarin up to 2-fold, both in microsomes and in perfused liver. Analysis of the perfusate showed that the increased amounts of p-nitrophenol and 7-hydroxycoumarin produced by the elevated mixed-function oxidase activities were reflected by the increase in the amounts of glucuronide conjugates and not in the increase for the amounts of the sulfate ester conjugates. Comparison of results also indicated that in the perfused liver, the maximal rate of metabolite conjugation is limited by the maximal rates of the initial mixed function oxidase activities.

Keyword

Mixed-function oxidation; conjugation enzyme reactions; antioxidants (BHA, BHT); perfused liver

MeSH Terms

Alkylation
Animal
Anisoles/metabolism
Anisoles/pharmacology*
Butylated Hydroxyanisole/administration & dosage
Butylated Hydroxyanisole/pharmacology*
Butylated Hydroxytoluene/administration & dosage
Butylated Hydroxytoluene/analogs & derivatives*
Butylated Hydroxytoluene/pharmacology
Comparative Study
Coumarins/metabolism
Female
Glucuronosyltransferase/metabolism
Liver/metabolism*
Mice
Microsomes, Liver/enzymology
Microsomes, Liver/metabolism*
Mixed Function Oxygenases/metabolism
Oxidation-Reduction
Perfusion
Support, U.S. Gov't, P.H.S.