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Toxicokinetics of HT-2 toxin in rats and its metabolic profile in livestock and human liver microsomes

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Abstract
The lack of information on HT-2 toxin leads to inaccurate hazard evaluations. In the present study, toxicokinetic studies of HT-2 toxin were investigated following intravenous (iv) and oral administration to rats at dosages of 1.0 mg per kilogram of body weight. After oral administration, HT-2 toxin was not detected in plasma, whereas its hydroxylated metabolite, 3'-OH HT-2 was identified. Following iv administration, HT-2 toxin; its 3'-hydroxylated product; and its glucuronide derivative, 3-G1cA HT-2, were observed in plasma, and the glucuronide conjugate was the predominant metabolite. To explore the missing HT-2 toxin in plasma, metabolic studies of HT-2 toxin in liver microsomes were conducted. Consequently, eight phase I and three phase II metabolites were identified. Hydroxylation, hydrolysis, and glucuronidation were the main metabolic pathways, among which hydroxylation was the predominant one, mediated by 3A4, a cytochrome P450 enzyme. Additionally, significant interspecies metabolic differences were observed.
Keywords
bioavailability, metabolism, phenotype, mycotoxin, risk assessment, T-2 TOXIN, IN-VITRO, TRICHOTHECENE MYCOTOXINS, FUSARIUM MYCOTOXINS, MASS-SPECTROMETRY, BROILER-CHICKENS, ANIMAL-TISSUES, BIOTRANSFORMATION, DEOXYNIVALENOL, CYTOTOXICITY

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MLA
Yang, Shupeng, et al. “Toxicokinetics of HT-2 Toxin in Rats and Its Metabolic Profile in Livestock and Human Liver Microsomes.” JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 66, no. 30, 2018, pp. 8160–68, doi:10.1021/acs.jafc.8b02893.
APA
Yang, S., Zhang, H., De Boevre, M., Zhang, J., Li, Y., Zhang, S., … Sun, F. (2018). Toxicokinetics of HT-2 toxin in rats and its metabolic profile in livestock and human liver microsomes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 66(30), 8160–8168. https://doi.org/10.1021/acs.jafc.8b02893
Chicago author-date
Yang, Shupeng, Huiyan Zhang, Marthe De Boevre, Jinzhen Zhang, Yanshen Li, Suxia Zhang, Sarah De Saeger, Jinhui Zhou, Yi Li, and Feifei Sun. 2018. “Toxicokinetics of HT-2 Toxin in Rats and Its Metabolic Profile in Livestock and Human Liver Microsomes.” JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 66 (30): 8160–68. https://doi.org/10.1021/acs.jafc.8b02893.
Chicago author-date (all authors)
Yang, Shupeng, Huiyan Zhang, Marthe De Boevre, Jinzhen Zhang, Yanshen Li, Suxia Zhang, Sarah De Saeger, Jinhui Zhou, Yi Li, and Feifei Sun. 2018. “Toxicokinetics of HT-2 Toxin in Rats and Its Metabolic Profile in Livestock and Human Liver Microsomes.” JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 66 (30): 8160–8168. doi:10.1021/acs.jafc.8b02893.
Vancouver
1.
Yang S, Zhang H, De Boevre M, Zhang J, Li Y, Zhang S, et al. Toxicokinetics of HT-2 toxin in rats and its metabolic profile in livestock and human liver microsomes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY. 2018;66(30):8160–8.
IEEE
[1]
S. Yang et al., “Toxicokinetics of HT-2 toxin in rats and its metabolic profile in livestock and human liver microsomes,” JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 66, no. 30, pp. 8160–8168, 2018.
@article{8582864,
  abstract     = {{The lack of information on HT-2 toxin leads to inaccurate hazard evaluations. In the present study, toxicokinetic studies of HT-2 toxin were investigated following intravenous (iv) and oral administration to rats at dosages of 1.0 mg per kilogram of body weight. After oral administration, HT-2 toxin was not detected in plasma, whereas its hydroxylated metabolite, 3'-OH HT-2 was identified. Following iv administration, HT-2 toxin; its 3'-hydroxylated product; and its glucuronide derivative, 3-G1cA HT-2, were observed in plasma, and the glucuronide conjugate was the predominant metabolite. To explore the missing HT-2 toxin in plasma, metabolic studies of HT-2 toxin in liver microsomes were conducted. Consequently, eight phase I and three phase II metabolites were identified. Hydroxylation, hydrolysis, and glucuronidation were the main metabolic pathways, among which hydroxylation was the predominant one, mediated by 3A4, a cytochrome P450 enzyme. Additionally, significant interspecies metabolic differences were observed.}},
  author       = {{Yang, Shupeng and Zhang, Huiyan and De Boevre, Marthe and Zhang, Jinzhen and Li, Yanshen and Zhang, Suxia and De Saeger, Sarah and Zhou, Jinhui and Li, Yi and Sun, Feifei}},
  issn         = {{0021-8561}},
  journal      = {{JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}},
  keywords     = {{bioavailability,metabolism,phenotype,mycotoxin,risk assessment,T-2 TOXIN,IN-VITRO,TRICHOTHECENE MYCOTOXINS,FUSARIUM MYCOTOXINS,MASS-SPECTROMETRY,BROILER-CHICKENS,ANIMAL-TISSUES,BIOTRANSFORMATION,DEOXYNIVALENOL,CYTOTOXICITY}},
  language     = {{eng}},
  number       = {{30}},
  pages        = {{8160--8168}},
  title        = {{Toxicokinetics of HT-2 toxin in rats and its metabolic profile in livestock and human liver microsomes}},
  url          = {{http://dx.doi.org/10.1021/acs.jafc.8b02893}},
  volume       = {{66}},
  year         = {{2018}},
}

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