The roles of carboxylesterase and CYP isozymes on the <italic style="font-style: italic">in vitro</italic> metabolism of T-2 toxin

Ni-ni Lin; Jia Chen; Bin Xu; Xia Wei; Lei Guo; Jian-wei Xie

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The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin

RESEARCH | Updated：2026-03-12

- The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin
- Military Medical Research Vol. 2, Issue 1, Pages: 21-27(2015)
- Affiliations：
  
  State Key Laboratory of Toxicology and Medical Countermeasures, and Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
- Author bio：
  
  *: Lei Guo, Email: guolei@bmi.ac.cn;
  Jian-Wei Xie, Email: xiejw@bmi.ac.cn
- Funds：
- DOI：
  CLC：
- Published：2015-03
- Accepted：
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Ni-ni Lin, Jia Chen, Bin Xu, et al. The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin[J]. Military Medical Research, 2015, 2(1): 21-27.
DOI：

Ni-ni Lin, Jia Chen, Bin Xu, et al. The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin[J]. Military Medical Research, 2015, 2(1): 21-27. DOI：

摘要

Abstract

Background:

T-2 toxin poses a great threat to human health because it has the highest toxicity of the currently known trichothecene mycotoxins. To understand the in vivo toxicity and transformation mechanism of T-2 toxin

we investigated the role of two principal phase Ⅰ drug-metabolizing enzymes (cytochrome P450 [CYP450] enzymes) on the metabolism of T-2 toxin

which are crucial to the metabolism of endogenous substances and xenobiotics. We also investigated carboxylesterase

which also plays an important role in the metabolism of toxic substances.

Methods:

A chemical inhibition method and a recombinant method were employed to investigate the metabolism of the T-2 toxin by the CYP450 enzymes

and a chemical inhibition method was used to study carboxylesterase metabolism. Samples incubated with human liver microsomes were analyzed by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC- QqQ MS) after a simple pretreatment.

Results:

In the presence of a carboxylesterase inhibitor

only 20% T-2 toxin was metabolized. When CYP enzyme inhibitors and a carboxylesterase inhibitor were both present

only 3% of the T-2 toxin was metabolized. The contributions of the CYP450 enzyme family to T-2 toxin metabolism followed the descending order CYP3A4

CYP2E1

CYP1A2

CYP2B6 or CYP2D6 or CYP2C19.

Conclusions:

Carboxylesterase and CYP450 enzymes are of great importance in T-2 toxin metabolism

in which carboxylesterase is predominant and CYP450 has a subordinate role. CYP3A4 is the principal member of the CYP450 enzyme family responsible for T-2 toxin metabolism. The metabolite produced by carboxylesterase is HT-2

and the metabolite produced by CYP 3A4 is 3’-OH T-2. The different metabolites show different toxicities. Our results will provide useful data concerning the toxic mechanism

the safety evaluation

and the health risk assessment of T-2 toxin.

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The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin

DOI：

摘要

Abstract

关键词

Keywords

references