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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, Huiyan Zhang, Marthe De Boevre, 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 66.30 (2018): 8160–8168. Print.
APA
Yang, Shupeng, Zhang, H., De Boevre, M., Zhang, J., Li, Y., Zhang, S., De Saeger, S., et al. (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.
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): 8160–8168.
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.
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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