Aflatoxin B1 metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents

Jiang Deng; Ling Zhao; Ni-Ya Zhang; Niel Alexander Karrow; Christopher Steven Krumm; De-Sheng Qi; Lv-Hui Sun

doi:10.1016/j.mrrev.2018.10.002

Aflatoxin B₁ metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents

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

Authors

Jiang Deng¹, Ling Zhao², Ni-Ya Zhang¹, Niel Alexander Karrow³, Christopher Steven Krumm⁴, De-Sheng Qi¹, Lv-Hui Sun⁵

Affiliations

¹ Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
² 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.
³ Department of Animal Biosciences, University of Guelph, Guelph, ON, N1G 2W1, Canada.
⁴ Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, United States.
⁵ Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address: lvhuisun@mail.hzau.edu.cn.

PMID: 30454686
DOI: 10.1016/j.mrrev.2018.10.002

Abstract

Aflatoxin B₁ (AFB₁) 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 AFB₁ 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 AFB₁ to the extremely toxic exo-AFB₁-8,9-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 AFB₁ 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 AFB₁ 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 AFB₁ among humans, experimental and farm animals, as well as the chemoprotective agents that can be used to minimize risk of aflatoxicosis.

Keywords: Aflatoxin B(1); Chemoprotective agent; Metabolism; Phase I metabolizing enzymes; Phase II metabolizing enzymes.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aflatoxin B1 / genetics
Aflatoxin B1 / metabolism*
Animals
Cattle
Cytochrome P-450 CYP1A2 / genetics
Humans
Inactivation, Metabolic / genetics*
Metabolic Detoxication, Phase I / genetics*
Mice

Substances

Aflatoxin B1
Cytochrome P-450 CYP1A2