Determination of benchmark doses for linear furanocoumarin consumption associated with inhibition of cytochrome P450 1A2 isoenzyme activity in healthy human adults.
Determination of benchmark doses for linear furanocoumarin consumption associated with inhibition of cytochrome P450 1A2 isoenzyme activity in healthy human adults.
复制标题
DOI：
10.1016/j.toxrep.2021.07.013
复制
发表时间：
2021
影响因子：
--
通讯作者：
Matou-Nasri S
中科院分区：
文献类型：
--
作者：
Alehaideb Z;Matou-Nasri S
呋喃香豆素类是A. majus和A.大天使体外抑制效力似乎与CYP 1A 2活性相加。测定人呋喃香豆素消耗和CYP 1A 2抑制的BMD。全球数百万人食用传统草药（THMs），其中含有大量的线性呋喃香豆素。线性呋喃香豆素（即，8-甲氧基补骨脂素、5-甲氧基补骨脂素和异茴芹素）是细胞色素P450（CYP）同工酶的抑制剂，包括1A 2，1A 2是参与药物代谢和致癌物生物活化的主要酶。尽管含有呋喃香豆素的THMs的消费量很高，但没有研究测量了呋喃香豆素的消费水平，触发了对人类CYP 1A 2活性的抑制。第一个目的是使用浓度相加和全混合物化学混合物评估模型，验证三种呋喃香豆素类药物的效价是否对体外CYP 1A 2活性抑制具有相加作用。第二个目的是确定呋喃香豆素口服剂量混合物的基准剂量（BMD），表示为8-MOP当量，并评估体内CYP 1A 2活性，表示为抑制百分比。体外结果表明，三种呋喃香豆素抑制效力在THM提取物中是相加的，验证了在总呋喃香豆素剂量当量计算中使用浓度相加模型。使用USEPA BMD软件，BMD为18.9 μg 8-MOP当量/kg体重。这些信息对于呋喃香豆素相关的健康评估研究和THMs的监管至关重要。应对其余主要代谢酶进行进一步研究，以完善含呋喃香豆素的THMs的安全性，并提供准确的警告标签。
Furanocoumarins are the main CYP1A2 inhibitors in A. majus and A. archangelica. The inhibitory potencies appear additive to CYP1A2 activity in vitro. BMD determination for human furanocoumarin-consumption and CYP1A2 inhibition. Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins (i.e., 8-methoxypsoralen, 5-methoxypsoralen, and isopimpinellin) are inhibitors of cytochrome P450 (CYP) isoenzymes including 1A2, a major enzyme involved in drug metabolism and carcinogen bioactivation. Despite the high consumption of furanocoumarin-containing THMs, no studies have measured the furanocoumarin consumption level that triggers an inhibition to CYP1A2 activity in humans. The first objective was to verify if the potencies of the three furanocoumarins are additive towards the inhibition of CYP1A2 activity in vitro using concentration-addition and whole-mixture chemical-mixture-assessment models. A second objective was to determine the benchmark dose (BMD) with the mixtures of furanocoumarin oral doses, expressed as 8-MOP equivalents, and to assess the in vivo CYP1A2 activity, expressed as inhibition percentages. The in vitro results indicated that the three furanocoumarin inhibitory potencies were additive in the THM extracts, validating the use of the concentration-addition model in total furanocoumarin dose-equivalent calculations. Using the USEPA BMD software, the BMD was 18.9 μg 8-MOP equivalent/kg body weight. This information is crucial for furanocoumarin-related health-assessment studies and the regulation of THMs. Further studies should be performed for the remaining major metabolic enzymes to complete the safety profile of furanocoumarin-containing THMs and to provide accurate warning labelling.
登录
查看更多内容
影响因子：
4.3
作者：
Fotland, T. O.;Paulsen, J. E.;Husoy, T.
通讯作者：
Husoy, T.
DOI：
10.1007/s10930-011-9350-0
发表时间：
2011-10
期刊：
The protein journal
影响因子：
--
作者：
Kang AY;Young LR;Dingfelder C;Peterson S
通讯作者：
Peterson S
影响因子：
2.5
作者：
Carrillo, JA;Christensen, M;Bertilsson, L
通讯作者：
Bertilsson, L
影响因子：
3.8
作者：
Davis, J. Allen;Gift, Jeffrey S.;Zhao, Q. Jay
通讯作者：
Zhao, Q. Jay
影响因子：
3.3
作者：
Barlow, Susan;Chesson, Andrew;Vannier, Philippe
通讯作者：
Vannier, Philippe