title: Unraveling the in vitro and in vivo metabolism of diacetoxyscirpenol in various animal species and human using ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry.
abstract: Diacetoxyscirpenol (DAS), a Fusarium mycotoxin belonging to the trichothecene type A mycotoxins, is able to contaminate food and feed worldwide. Only limited information is available regarding the metabolism of DAS. The present study used ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UHPLC-Q/TOF) to investigate the in vitro phase I and II metabolism of DAS by rat, chicken, swine, goat, cow, and human liver microsomes. An extensive metabolization profile of DAS has been observed. A total of seven phase I and three phase II metabolites of DAS were detected. Among the identified molecules, four phase I metabolites (8β-hydroxy-DAS, neosolaniol, 7-hydroxy-DAS, and its epimer) and two phase II metabolites (4-deacetyl-DAS-3-glucuronic acid and 4-deacetyl-DAS-4-glucuronic acid) were identified for the first time. These results indicate that the major metabolic pathways of DAS in vitro were hydrolyzation (M1-M3), hydroxylation (M4-M7), and conjugation (M8-M10). Qualitative differences in phase I and II metabolic profiles of DAS between the five animal species and human were observed. 4-Deacetyl-DAS was the primary metabolite from liver microsomes of all species, especially human. The in vivo metabolism of DAS in rats and chickens after oral administration of DAS was also investigated and compared. The major metabolites for rats and chickens were 4-deacetyl-DAS and 7-hydroxy-DAS. These results will help to gain a more detailed insight into the metabolism and toxicity of DAS among different animal species and human. Graphical Abstract The metabolism of diacetoxyscirpenol in farm animals and human.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Marthe
authors.initials: M
authors.lastname: De Boevre
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: De Ruyck
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Cao
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: De Saeger
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, National Reference Laboratory of Veterinary Drug Residues, Beijing, 100193, China. suxia@cau.edu.cn.
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D002645:Chickens; D005260:Female; D005506:Food Contamination / Q000032:analysis; D006041:Goats; D006801:Humans; D006868:Hydrolysis; D006900:Hydroxylation; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000502:physiology*; D050217:Metabolic Detoxication, Phase II / Q000502:physiology*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D009183:Mycotoxins / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000295:instrumentation / Q000379:methods*; D013552:Swine; D014255:Trichothecenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics*
chemical_list: D009183:Mycotoxins; D014255:Trichothecenes; C001809:diacetoxyscirpenol
keywords: Animal; Diacetoxyscirpenol; Human; Metabolism; Phase I and II metabolites; UHPLC-Q/TOF