二（3,5-二叔丁基-4-羟基苄基）醚（抗氧剂201）在大鼠体内的代谢

The metabolism of di-(3,5-di-tert.-butyl-4-hydroxybenzyl) ether (Ionox 201) in the rat.

作者信息

Wright A S, Crowne R S, Hathway D E

出版信息

Biochem J. 1967 Jan;102(1):351-61. doi: 10.1042/bj1020351.

DOI:10.1042/bj1020351

PMID:6030293

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1270246/

Abstract

Up to one-third of a single oral dose of Ionox 201 was absorbed in rats. 2. In rats dosed with [(14)C]Ionox 201 86.8-97.2% of the label is excreted in the faeces in 24 days (much of this is eliminated in the first 4 days after dosage), 5.6% in the urine and not more than 0.8% in the exhaled air; 5.0% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 3. About 65.0% of (14)C in the faeces is due to unchanged antioxidant, 30.0% to 3,5-di-tert.-butyl-4-hydroxybenzoic acid, 3.5% to unidentified polar constituent(s), 1.4% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde and 0.1% to 3,3',5,5'-tetra-tert.-butyl-4-,4'-stilbenequinone. A variable proportion of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid (40-60%) and the remainder (60-40%) to the ester glucuronide, when the animals were treated with different doses of antioxidant. In eight individual animals dosed with 6.78mg. of [(14)C]Ionox 201, one-third of (14)C in the bile is due to the free acid, 45% to the ester glucuronide, 20% to an unidentified constituent and 2% to unchanged antioxidant, and, in two animals dosed with 13.56mg., there is a small proportion of free acid and a larger proportion of ester glucuronide. About 80% of (14)C in the body fat is due to unchanged antioxidant, 19% to the free acid and 1% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde. 4. At least 36.2% of a single oral dose of Ionox 201 is metabolized: 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 30.2% of a dose, (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 1.4%, 3,5-di-tert.-butyl-4-hydroxybenzaldehyde for 1.3%, 3,3',5,5'-tetra-tert.-butyl-4,4'-stilbenequinone for 0.1% and unidentified polar metabolite(s) for 3.2%. 5. The metabolism of Ionox 201 in vivo is closely related to its antioxidant action in vitro.

摘要

大鼠单次口服剂量的Ionox 201，高达三分之一可被吸收。2. 给大鼠服用[¹⁴C]Ionox 201后，86.8 - 97.2%的放射性标记物在24天内随粪便排出（其中大部分在给药后的前4天排出），5.6%经尿液排出，呼出气体中排出量不超过0.8%；去除肠道后， carcass和内脏中¹⁴C的含量为5.0%，其中大部分存在于脂肪组织中。3. 粪便中约65.0%的¹⁴C归因于未变化的抗氧化剂，30.0%归因于3,5 - 二叔丁基 - 4 - 羟基苯甲酸，3.5%归因于未鉴定的极性成分，1.4%归因于3,5 - 二叔丁基 - 4 - 羟基苯甲醛，0.1%归因于3,3',5,5'-四叔丁基 - 4,4'- 二苯乙烯醌。当动物接受不同剂量的抗氧化剂治疗时，尿液中¹⁴C的可变比例归因于3,5 - 二叔丁基 - 4 - 羟基苯甲酸（40 - 60%），其余部分（60 - 40%）归因于酯葡萄糖醛酸。在八只分别服用6.78mg [¹⁴C]Ionox 201的动物中，胆汁中三分之一的¹⁴C归因于游离酸，45%归因于酯葡萄糖醛酸，20%归因于未鉴定的成分，2%归因于未变化的抗氧化剂；在两只服用13.56mg的动物中，游离酸比例较小，酯葡萄糖醛酸比例较大。体内脂肪中约80%的¹⁴C归因于未变化的抗氧化剂，19%归因于游离酸，1%归因于3,5 - 二叔丁基 - 4 - 羟基苯甲醛。4. 单次口服剂量的Ionox 201至少36.2%被代谢：3,5 - 二叔丁基 - 4 - 羟基苯甲酸占剂量的30.2%，（3,5 - 二叔丁基 - 4 - 羟基苯甲酰基β - D - 吡喃葡萄糖苷）尿酸占1.4%，3,5 - 二叔丁基 - 4 - 羟基苯甲醛占1.3%，3,3',5,5'-四叔丁基 - 4,4'- 二苯乙烯醌占0.1%，未鉴定的极性代谢物占3.2%。5. Ionox 201在体内的代谢与其在体外的抗氧化作用密切相关。