黄曲霉毒素 B 代谢：I 期和 II 期代谢酶和化学保护剂的调节。

Aflatoxin B metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents.

机构信息

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province.

出版信息

Mutat Res Rev Mutat Res. 2018 Oct-Dec;778:79-89. doi: 10.1016/j.mrrev.2018.10.002. Epub 2018 Oct 29.

DOI:10.1016/j.mrrev.2018.10.002

PMID:30454686

Abstract

Aflatoxin B (AFB) widely contaminates staple food and feed crops and is well-known as the most potent natural hepatocarcinogen in humans and domesticated animals. This review highlights significant advances in our understanding of the pivotal role of phase I and II metabolizing enzymes in the bioactivation and detoxification of AFB and its metabolites across species. In humans, cytochrome P450 (CYP) 1A2, CYP3A4, CYP3A5, and CYP3A7 in liver and CYP2A13 in lung are essential for the bioactivation of AFB to the extremely toxic exo-AFB-8,9-epoxide (AFBO), whereas CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are important in the turkey and duck, CYP1A1 and CYP2A6 are important in the chicken and quail, CYP3A11 and CYP3A13 are important in mice, and CYP2A5 are important in the hamster. In contrast, glutathione-S-transferase (GST) M1 and GSTT1 are primary responsible for detoxification of the AFB by catalyzing the conjugation of GSH to AFBO in humans, whereas GSTM2 in a nonhuman primate, GSTA3 in mice, GSTA5 in rats, and GSTA1, GSTA2, GSTA3 and GSTA4 in the turkey are important. Additionally, microsomal epoxide hydrolase (mEH) and aflatoxin-aldehyde reductase (AFAR) have also been shown to play key roles in AFB detoxification in the human, rat, and pig. Moreover, an overview of the chemoprotective agents, including synthetic compounds and naturally occurring plant compounds, which can be used to reduce aflatoxicosis is provided based on their ability to regulate these key enzymes. Collectively, this review summarizes the pivotal enzymes in the metabolism of AFB among humans, experimental and farm animals, as well as the chemoprotective agents that can be used to minimize risk of aflatoxicosis.

摘要

黄曲霉毒素 B（AFB）广泛污染主食和饲料作物，是人类和家养动物中最有效的天然肝癌致癌物。本综述重点介绍了在理解 I 相和 II 相代谢酶在物种间 AFB 及其代谢物的生物活化和解毒中的关键作用方面的重要进展。在人类中，肝脏中的细胞色素 P450（CYP）1A2、CYP3A4、CYP3A5 和 CYP3A7 以及肺中的 CYP2A13 对于将 AFB 生物转化为极其有毒的外消旋-AFB-8,9-环氧化物（AFBO）至关重要，而 CYP1A1、CYP1A2、CYP2A6 和 CYP3A4 在火鸡和鸭中很重要，CYP1A1 和 CYP2A6 在鸡和鹌鹑中很重要，CYP3A11 和 CYP3A13 在小鼠中很重要，CYP2A5 在仓鼠中很重要。相比之下，谷胱甘肽-S-转移酶（GST）M1 和 GSTT1 主要负责通过催化 GSH 与 AFBO 结合来解毒 AFB，而非人类灵长类动物中的 GSTM2、小鼠中的 GSTA3、大鼠中的 GSTA5 以及火鸡中的 GSTA1、GSTA2、GSTA3 和 GSTA4 很重要。此外，微粒体环氧化物水解酶（mEH）和黄曲霉毒素醛还原酶（AFAR）也被证明在人类、大鼠和猪的 AFB 解毒中发挥关键作用。此外，根据其调节这些关键酶的能力，提供了用于减少黄曲霉毒素中毒的化学保护剂，包括合成化合物和天然存在的植物化合物。总的来说，本综述总结了人类、实验动物和农场动物中 AFB 代谢的关键酶以及可用于最小化黄曲霉毒素中毒风险的化学保护剂。