T-2 toxin metabolism and its hepatotoxicity: New insights on the molecular mechanism and detoxification

Song, Wenxi; Wang, Youshuang; Huang, Tingyu; Yu, Lei; Chen, Fengjuan; Chen, Yunhe; Jiang, Yibao; Zhang, Cong; Yang, Xu

doi:10.1016/j.envpol.2023.121784

Cited by 15 publications

(7 citation statements)

References 57 publications

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“…However, a variety of results have also been reported depending on the cell species. For example, the enzyme that plays the main role in the metabolism of T-2 is CYP1A1 in Caco-2 cells [31], CYP3A4 and CYP1A1 in HepG2 cells [15,24,32,33] and CYP3A46 in porcine primary hepatocytes [34].…”

Section: Identification Of T-2 and Its Metabolitesmentioning

confidence: 99%

“…Furthermore, combined toxic effects due to the coexposure of T-2 and its metabolites should also be considered because these combinations exhibit varying degrees of cytotoxicity compared to mycotoxins ingested individually, with stronger cytotoxicity, as recently reviewed by Skrzydlewski and colleagues [37]. Even at these doses, the toxic effects are notable, which could involve activation of oxidative stress, mitochondrial damage, abnormal DNA methylation, autophagy and apoptosis, as recently reviewed in the literature [33,35]. This is also highlighted by the results of a study carried out at low doses of T-2 (50% LOAEL); they found that T-2 reduces the synthesis of anti-inflammatory cytokines such as TGF-β and increases the secretion of proinflammatory cytokines, compromising the integrity of the intestinal mucosal barrier [36].…”

Section: Identification Of T-2 and Its Metabolitesmentioning

confidence: 99%

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

Taroncher,

Zingales,

Rodríguez-Carrasco

et al. 2024

Foods

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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 (IC50/2) and 60 (IC50) 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 (p < 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.

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Section: Identification Of T-2 and Its Metabolitesmentioning

confidence: 99%

Section: Identification Of T-2 and Its Metabolitesmentioning

confidence: 99%

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

Taroncher,

Zingales,

Rodríguez-Carrasco

et al. 2024

Foods

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“…2 The generation of T-2 toxin is affected by the species, temperature, humidity, pH, illumination, and so on. 3 The generation of T-2 toxin when the temperature, humidity, or acidity are changed is beneficial. T-2 toxin primarily contaminates grain and foods made of grain; thus, T-2 toxin can harm the health of humans and animals.…”

Section: Introductionmentioning

confidence: 99%

“…T-2 toxin crystals were first isolated and purified from a Fusarium strain in 1968 by Bamburg, and the chemical composition of the T-2 toxin was confirmed (Figure ). The generation of T-2 toxin is affected by the species, temperature, humidity, pH, illumination, and so on . The generation of T-2 toxin when the temperature, humidity, or acidity are changed is beneficial.…”

Section: Introductionmentioning

confidence: 99%

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Zhang,

Song,

Hua

et al. 2024

J. Agric. Food Chem.

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Fusarium species produce a secondary metabolite known as T-2 toxin, which is the primary and most harmful toxin found in type A trichothecenes. T-2 toxin is widely found in food and grain-based animal feed and endangers the health of both humans and animals. T-2 toxin exposure in humans and animals occurs primarily through food administration; therefore, the first organ that T-2 toxin targets is the gut. In this overview, the research progress, toxicity mechanism, and detoxification of the toxin T-2 were reviewed, and future research directions were proposed. T-2 toxin damages the intestinal mucosa and destroys intestinal structure and intestinal barrier function; furthermore, T-2 toxin disrupts the intestinal microbiota, causes intestinal flora disorders, affects normal intestinal metabolic function, and kills intestinal epidermal cells by inducing oxidative stress, inflammatory responses, and apoptosis. The primary harmful mechanism of T-2 toxin in the intestine is oxidative stress. Currently, selenium and plant extracts are mainly used to exert antioxidant effects to alleviate the enterotoxicity of T-2 toxin. In future studies, the use of genomic techniques to find upstream signaling molecules associated with T-2 enterotoxin toxicity will provide new ideas for the prevention of this toxicity. The purpose of this paper is to review the progress of research on the intestinal toxicity of T-2 toxin and propose new research directions for the prevention and treatment of T-2 toxin toxicity.

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“…13, x FOR PEER REVIEW 11 of 18mycotoxin is metabolized and excreted by HepG2 cells. The choice of enzymes was guided by prior reports of the liver metabolism of T-2 and other trichothecenes[48][49][50].…”

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confidence: 99%

Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin

Taroncher,

Gonzalez-Suarez,

Gwon

et al. 2024

Cells

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The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2.

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T-2 toxin metabolism and its hepatotoxicity: New insights on the molecular mechanism and detoxification

Cited by 15 publications

References 57 publications

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

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

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin

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