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使用液相色谱-四极杆飞行时间质谱法鉴定 HepG2 细胞中 T-2 毒素的生物转化产物

Identification of Biotransformation Products of T-2 Toxin in HepG2 Cells Using LC-Q-TOF MS.

作者信息

Taroncher Mercedes, Zingales Veronica, Rodríguez-Carrasco Yelko, Ruiz María José

机构信息

Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Science, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.

Research Group Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox; GIUV2021-513), University of Valencia, 46100 València, Spain.

出版信息

Foods. 2024 May 13;13(10):1501. doi: 10.3390/foods13101501.

DOI:10.3390/foods13101501
PMID:38790801
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11120489/
Abstract

The T-2 toxin (T-2) is a type A trichothecene found in cereals. The formation of metabolites is a frequent cause of mycotoxin-induced toxicity. In this work, the conversion of T-2 during biotransformation reactions in HepG2 cells was evaluated. For this, HepG2 cells were exposed to 30 (IC/2) and 60 (IC) nM of T-2 for 0, 1, 2, 3, 6, 8 and 24 h, and the concentrations of T-2 and its metabolites HT-2, T2-triol, T2-tetraol and neosolaniol were determined in both the cell fraction and culture medium through liquid chromatography coupled to high-resolution mass spectrometry-time of flight (LC-Q-TOF MS). Results showed a fast metabolization of T-2 (>90%) during the first 2 h, with HT-2 as its main (>95%) biotransformation product. The cell fraction showed higher levels ( < 0.05) of HT-2 (39.9 ± 2.1 nM) compared to the culture medium (12.53 ± 2.4 nM). This trend was also observed for the identified metabolites. T2-triol reached its maximum concentration (1.7 ± 0.4 nM) at 2 h, and at later times a time-dependent increase in the T2-tetraol and neosolaniol concentrations was observed. The identification of T-2 metabolites shows the need to continue combined toxicity studies of mycotoxins for a correct risk characterization of these natural contaminants.

摘要

T-2毒素(T-2)是一种在谷物中发现的A型单端孢霉烯族毒素。代谢产物的形成是霉菌毒素诱导毒性的常见原因。在这项研究中,评估了T-2在HepG2细胞生物转化反应中的转化情况。为此,将HepG2细胞暴露于30(IC/2)和60(IC)nM的T-2中0、1、2、3、6,、8和24小时,并通过液相色谱-高分辨率质谱-飞行时间联用(LC-Q-TOF MS)测定细胞组分和培养基中T-2及其代谢产物HT-2、T2-三醇、T2-四醇和新茄病镰刀菌烯醇的浓度。结果表明,在最初2小时内T-2快速代谢(>90%),HT-2是其主要(>95%)生物转化产物。与培养基(12.53±2.4 nM)相比,细胞组分中HT-2的水平更高(<0.05)(39.9±2.1 nM)。在所鉴定的代谢产物中也观察到了这种趋势。T2-三醇在2小时时达到最大浓度(1.7±0.4 nM),在随后的时间里,观察到T2-四醇和新茄病镰刀菌烯醇浓度随时间增加。T-2代谢产物的鉴定表明,需要继续开展霉菌毒素的联合毒性研究,以便对这些天然污染物进行正确的风险特征描述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/6fff8bec8179/foods-13-01501-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/91e92f8d6b00/foods-13-01501-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/1c890d529595/foods-13-01501-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/cff17686e4d5/foods-13-01501-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/eb100bb6dcd6/foods-13-01501-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/5db9c4c338e4/foods-13-01501-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/6fff8bec8179/foods-13-01501-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/91e92f8d6b00/foods-13-01501-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/1c890d529595/foods-13-01501-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/cff17686e4d5/foods-13-01501-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/5bd596efbb82/foods-13-01501-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/eb100bb6dcd6/foods-13-01501-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/5db9c4c338e4/foods-13-01501-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/11120489/6fff8bec8179/foods-13-01501-g007.jpg

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本文引用的文献

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T-2 toxin metabolism and its hepatotoxicity: New insights on the molecular mechanism and detoxification.T-2 毒素代谢及其肝毒性:分子机制与解毒的新见解。
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