1.Enhancements of Mouse Hepatic Cytosol Enzyme Activities Involved in UDP-Glucuronic Acid Synthesis, Glutathione Reduction and Conjugation with Butylated Hydroxyanisole (BHA) and Its Structural Analogs.
Young Nam CHA ; Jin Ho CHUNG ; Henry S HEINE ; Sa Suk HONG
Yonsei Medical Journal 1984;25(2):105-115
Activities of hepatic cytosol enzymes involved in UDP-g1ucuronic acid synthesis as well as in glutathione reduction and conjugation systems were determined following administrations of butylated hydroxyanisole (approximately 5 mmol/kg body weight/day) and of equimolar intake doses of its structural anglogs. These compounds included the multi-functional group side chain compounds (t-butyl hydroquinone, 4-hydroxy- anisole, hydroquinone, benzoquinone) and the mono-functional side chain compounds (t-butyl benzene, anisole, phenol). They were administered to mice for 10 days either by mixing them in the diet or by oral intubations. Results showed that glutathione Stransferase activities were markedly increased by all tested compounds except for the t-butyl benzene. Activities of glutathione reductase and glucose 6-phosphate dehydrogenase were increased together on1y by BHA and t-butyl hydroguinone. UDP-glucose dehydrogenase and NADH:quinone reductase activities were significantly elevated by the multi-functional side chain compounds, but not by the mono-functional analogs. The relations between chemical structures of tested BHA analogs and elevations of the measured hepatic cytosol conjugation (detoxification) system enzyme activities for the metabolism and excretion of BHA analogs are discussed.
Animal
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Anisoles/metabolism*
;
Butylated Hydroxyanisole/analogs & derivatives
;
Butylated Hydroxyanisole/metabolism*
;
Cytosol/enzymology*
;
Glutathione/metabolism*
;
Mice
;
Uridine Diphosphate Glucuronic Acid/biosynthesis*
;
Uridine Diphosphate Sugars/biosynthesis*
2.Enhancement of O-dealkylation in Mouse Liver by Dietary Administrations of BHA and BHT: Studies with Isolated Perfused Livers and Hepatic Microsomes.
Sung Chul JI ; James G CONWAY ; Ronald G THURMAN ; Young Nam CHA
Yonsei Medical Journal 1986;27(2):106-113
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.
Alkylation
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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
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Support, U.S. Gov't, P.H.S.